query: which cells with in the islets of langerhans secrete insulin

pos: Pancreatic islets µm) in diameter. Each is separated from the surrounding pancreatic tissue by a thin fibrous connective tissue capsule which is continuous with the fibrous connective tissue that is interwoven throughout the rest of the pancreas. Hormones produced in the pancreatic islets are secreted directly into the blood flow by (at least) five types of cells. In rat islets, endocrine cell subsets are distributed as follows: It has been recognized that the cytoarchitecture of pancreatic islets differs between species. In particular, while rodent islets are characterized by a predominant proportion of insulin-producing beta cells in the core of the cluster and

pos: Proinsulin Proinsulin Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the "INS" gene. The islets of Langerhans only secrete between 1% and 3% of proinsulin intact. However, because proinsulin has a longer half life than insulin, it can account for anywhere from 5–30% of the insulin-like structures circulating in the blood. There are higher concentrations of proinsulin after meals and lower levels when a person is fasting. Additionally, while proinsulin and insulin have structural differences, proinsulin does demonstrate some affinity for

pos: Proinsulin only amino acid change mutations found in the B domain lead to the disease. Proinsulin Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the "INS" gene. The islets of Langerhans only secrete between 1% and 3% of proinsulin intact. However, because proinsulin has a longer half life than insulin, it can account for anywhere from 5–30% of the insulin-like structures circulating in the blood. There are higher concentrations of proinsulin after meals and lower levels when a person is fasting.

pos: Insulin oscillation oscillations. The insulin oscillations are generated by pulsatile release of the hormone from the pancreas. Insulin originates from beta cells located in the islets of Langerhans. Since each islet contains up to 2000 beta cells and there are one million islets in the pancreas it is apparent that pulsatile secretion requires sophisticated synchronization both within and among the islets of Langerhans. Pulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In beta cells lacking contact, the periodicity of these oscillations is rather variable (2-10 min). However, within an islet of Langerhans

pos: Glipizide 10 milligrams. Glipizide sensitizes the beta cells of pancreatic islets of Langerhans insulin response, meaning that more insulin is released in response to glucose than would be without glipizide ingestion. Glipizide acts by partially blocking potassium channels among beta cells of pancreatic islets of Langerhans. By blocking potassium channels, the cell depolarizes, which results in the opening of voltage-gated calcium channels. The resulting calcium influx encourages insulin release from beta cells. Glipizide Glipizide is an oral rapid- and short-acting anti-diabetic medication from the sulfonylurea class. It is classified as a second-generation sulfonylurea, which means that it undergoes enterohepatic circulation. Second-generation

pos: Diabetes management developed to target the psychological mechanisms underpinning adherence. By working on increasing motivation and challenging maladaptive illness perceptions, programs such as CBT-AD aim to enhance self-efficacy and improve diabetes-related distress and one's overall quality of life. Diabetes type 1 is caused by the destruction of enough beta cells to produce symptoms; these cells, which are found in the Islets of Langerhans in the pancreas, produce and secrete insulin, the single hormone responsible for allowing glucose to enter from the blood into cells (in addition to the hormone amylin, another hormone required for glucose homeostasis). Hence, the phrase "curing diabetes type

pos: Incretin been developed. In 1932, Belgian physiologist Jean La Barre used the word "incretin" for a gut hormone, which stimulates the endocrine pancreas including insulin release. He also proposed that such incretins could be used as a treatment for diabetes mellitus. Incretin Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism. Incretins also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow

pos: Pancreas secretion of enzymes involved in digesting substances from outside of the body. Approximately 3 million cell clusters called pancreatic islets are present in the pancreas. Within these islets are four main types of cells which are involved in the regulation of blood glucose levels. Each type of cell secretes a different type of hormone: α alpha cells secrete glucagon (increase glucose in blood), β beta cells secrete insulin (decrease glucose in blood), δ delta cells secrete somatostatin (regulates/stops α and β cells) and PP cells, or γ (gamma) cells, secrete pancreatic polypeptide. These act to control blood glucose through secreting

pos: Beta cell Beta cell Beta cells (β cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin. Beta cells make up 50-70% of the cells in human islets. In patients with type I or type II diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. The primary function of a beta cell is to produce and release insulin. Insulin is a hormone that brings about effects which reduce blood glucose concentration. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting some of their stored insulin while simultaneously producing

pos: Beta cell research is very active yet many mysteries remain. Beta cell Beta cells (β cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin. Beta cells make up 50-70% of the cells in human islets. In patients with type I or type II diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. The primary function of a beta cell is to produce and release insulin. Insulin is a hormone that brings about effects which reduce blood glucose concentration. Beta cells can respond quickly to spikes in blood glucose concentrations by secreting

pos: Incretin Incretin Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism. Incretins also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. The two main candidate molecules that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric

pos: Development of the endocrine system alpha cells. The insulin concentration within the fetal pancreas is 3.6 pmol/g at seven to ten weeks, which rises to 30 pmol/g at 16–25 weeks of gestation. Near term, the insulin concentration increases to 93 pmol/g. The endocrine cells have dispersed throughout the body within 10 weeks. At 31 weeks of development, the islets of Langerhans have differentiated. While the fetal pancreas has functional beta cells by 14 to 24 weeks of gestation, the amount of insulin that is released into the bloodstream is relatively low. In a study of pregnant women carrying fetuses in the mid-gestation and near term

pos: Diabetes mellitus type 1 According to the current definition, two fasting glucose measurements above 126 mg/dl (7.0 mmol/l) is considered diagnostic for diabetes mellitus. In type 1, pancreatic beta cells in the islets of Langerhans are destroyed, decreasing endogenous insulin production. This distinguishes type 1's origin from type 2. Type 2 diabetes is characterized by insulin resistance, while type 1 diabetes is characterized by insulin deficiency, generally without insulin resistance. Another hallmark of type 1 diabetes is islet autoreactivity, which is generally measured by the presence of autoantibodies directed towards the beta cells. The appearance of diabetes-related autoantibodies has been shown to be able

pos: Diabetes mellitus of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in balancing glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen. Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used

pos: LMX1A LMX1A LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the "LMX1A" gene. Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas. The level and beta-cell specificity of insulin gene expression are regulated by a set of nuclear genes that bind to specific sequences within the promoter of the insulin gene "INS" and interact with RNA polymerase to activate or repress transcription. LMX1 is a LIM homeobox transcription factor that binds an A/T-rich sequence in the insulin promoter and stimulates transcription of insulin.

pos: Insulin signal transduction pathway synthesized and secreted in the beta cells of the islets of Langerhans. Once insulin is synthesized, the beta cells are ready to release it in two different phases. As for the first phase, insulin release is triggered rapidly when the blood glucose level is increased. The second phase is a slow release of newly formed vesicles that are triggered regardless of the blood sugar level. Glucose enters the beta cells and goes through glycolysis to form ATP that eventually causes depolarization of the beta cell membrane (as explained in Insulin secretion section of this article). The depolarization process causes voltage-controlled

pos: Insulitis Insulitis Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas. The islets containing the pancreatic β-cells, and in some cases, the exocrine tissues, become infiltrated by T and B lymphocytes, macrophages and dendritic cells. This innate immune cell and lymphocyte infiltration can result in destruction of the insulin producing beta cells of the islets, and clinical diabetes. Insulitis is often studied in the multiple low dose streptozotocin (MLDS) mouse model or the non-obese diabetic (NOD) mouse model of type 1 diabetes. The chemokine family of proteins may play a key role

pos: Pancreatic islets diabetes (ref GLP-1 receptor agonists, DPPIV inhibitors). Electrical activity of pancreatic islets has been studied using patch clamp techniques. It has turned out that the behavior of cells in intact islets differs significantly from the behavior of dispersed cells. The beta cells of the pancreatic islets secrete insulin, and so play a significant role in diabetes. It is thought that they are destroyed by immune assaults. However, there are also indications that beta cells have not been destroyed but have only become non-functional. Because the beta cells in the pancreatic islets are selectively destroyed by an autoimmune process in type

pos: Dopamine moves through the digestive system). The pancreatic islets make up the endocrine part of the pancreas, and synthesize and secrete hormones including insulin into the bloodstream. There is evidence that the beta cells in the islets that synthesize insulin contain dopamine receptors, and that dopamine acts to reduce the amount of insulin they release. The source of their dopamine input is not clearly established—it may come from dopamine that circulates in the bloodstream and derives from the sympathetic nervous system, or it may be synthesized locally by other types of pancreatic cells. Dopamine as a manufactured medication is sold under

pos: Insulitis in promoting leukocytic infiltration into the pancreas prior to pancreatic beta-cell destruction. Insulitis Insulitis is an inflammation of the islets of Langerhans, a collection of endocrine tissue located in the pancreas. The islets containing the pancreatic β-cells, and in some cases, the exocrine tissues, become infiltrated by T and B lymphocytes, macrophages and dendritic cells. This innate immune cell and lymphocyte infiltration can result in destruction of the insulin producing beta cells of the islets, and clinical diabetes. Insulitis is often studied in the multiple low dose streptozotocin (MLDS) mouse model or the non-obese diabetic (NOD) mouse model of type

pos: LMX1A LMX1A has been shown to interact with TCF3 and LHX3. LMX1A LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the "LMX1A" gene. Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas. The level and beta-cell specificity of insulin gene expression are regulated by a set of nuclear genes that bind to specific sequences within the promoter of the insulin gene "INS" and interact with RNA polymerase to activate or repress transcription. LMX1 is a LIM homeobox transcription factor that binds an A/T-rich

pos: Pancreas by Pax-6, produces beta cells (β-) and delta cells (δ-), which secrete insulin and somatostatin, respectively. Insulin and glucagon can be detected in the human fetal circulation by the fourth or fifth month of fetal development. The pancreas is involved in blood sugar control and metabolism within the body, and also in the secretion of substances (collectively pancreatic juice) which help digestion. Classically, these are divided into an "endocrine" role, relating to the secretion of insulin and other substances within pancreatic islets and helping control blood sugar levels and metabolism within the body, and an "exocrine" role, relating to the

pos: Insulin glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by hormone sensitive lipase in adipose tissue. Beta cells in the islets of Langerhans release insulin in two phases. The first-phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 10 minutes. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. Reduced first-phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes. First-phase release and insulin

pos: Insulin signal transduction pathway time. PTBPs, also called Polypyrimidine tract binding proteins, are proteins that regulate the translation of mRNA. They increase the viability of mRNA and provoke the initiation of the translation. PTBP1 enable the insulin gene specific activation and insulin granule protein mRNA by glucose. Two aspects of the transduction pathway process are explained below: insulin secretion and insulin action on the cell. The glucose that goes in the bloodstream after food consumption also enters the beta cells in the Islets of Langerhans in the pancreas. The glucose passively diffuses in the beta cell through a GLUT-2 vesicle. Inside the beta cell,

pos: Proinsulin form mature insulin. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds. The post translational modification of proinsulin to mature insulin only occurs in the beta cells of the islets of Langerhans. When proinsulin is transported through the Golgi apparatus the C-peptide is cleaved. This cleavage occurs with the aid of two endoproteases. Type I endoproteases, PC1 and PC3, disrupt the C peptide-B chain connection.

pos: ALOX12 the pancreas islets appear to be the major if not only site where ALOX12 is expressed in these patients. The studies propose that in the islets of Langerhans ALOX12 and its 12("S")-HETE product cause excessive production of reactive oxygen species and inflammation which lead to losses in insulin-secreting beta cells and thereby types 1 and 2 diabetes and that in adipose tissue the excess in AlOX12, 12("S")-HETE, reactive oxygen species, and inflammation lead to fat cell dysfunction (also see 12-HETE#Inflammation and inflammatory diseases and 12-HETE#Diabetes). Indeed, in one study a Single-nucleotide polymorphism, rs2073438, located in an intron region of the

pos: Pancreatic islets and transdifferentiate into beta cells in both healthy and diabetic human and mouse pancreatic islets, a possible future source for beta cell regeneration. Pancreatic islets The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1 to 2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose. There are about 3 million islets distributed in the

pos: Streptozotocin Streptozotocin Streptozotocin or streptozocin (INN, USP) (STZ) is a naturally occurring alkylating antineoplastic agent that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the islets of Langerhans and used in medical research to produce an animal model for hyperglycemia in a large dose, as well as type 2 diabetes or type 1 diabetes with multiple low doses. Streptozotocin is approved by the U.S. Food and Drug Administration (FDA) for treating metastatic cancer of the pancreatic islet cells. Since it carries a substantial risk of toxicity

pos: Blood sugar regulation or carbohydrate foods. It is often self-diagnosed and self-medicated orally by the ingestion of balanced meals. In more severe circumstances, it is treated by injection or infusion of glucagon. When levels of blood sugar rise, whether as a result of glycogen conversion, or from digestion of a meal, a different hormone is released from beta cells found in the Islets of Langerhans in the pancreas. This hormone, insulin, causes the liver to convert more glucose into glycogen (this process is called glycogenesis), and to force about 2/3 of body cells (primarily muscle and fat tissue cells) to take up glucose

pos: Paul Eston Lacy a Ph.D. in that discipline by the University of Minnesota in 1955. In 1955, Lacy was appointed assistant professor in the Department of Anatomy at Washington University School of Medicine, St. Louis, Missouri. He undertook research into the characterization of endocrine cells in the pancreas, using ultrastructural and fluorescent-antibody-labeling methods. That work resulted in a better understanding of how beta cells in the pancreatic islets of Langerhans produced and exported insulin, and it steadily propelled Lacy through the academic ranks. In 1961, Lacy was named the sixth chairman of Pathology at Washington University, having been preceded by Eugene Lindsay Opie,

pos: Beta cell and the development of obesity. The beta cells can still secrete insulin but the body has developed a resistance and its response to insulin has declined. It is believed to be due to the decline of specific receptors on the surface of the liver, adipose, and muscle cells which lose their ability to respond to insulin that circulates in the blood. In an effort to secrete enough insulin to overcome the increasing insulin resistance, the beta cells increase their function, size and number. Increased insulin secretion leads to hyperinsulinemia, but blood glucose levels remain within their normal range due to

pos: Vildagliptin Vildagliptin Vildagliptin (previously LAF237, trade names Galvus, Zomelis,) is an oral anti-hyperglycemic agent (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas. Vildagliptin has been shown to reduce hyperglycemia in type 2 diabetes mellitus. The European Medicines Agency has also approved a combination of vildagliptin and metformin, vildagliptin/metformin (Eucreas by Novartis) as an oral treatment for type-2 diabetes.

pos: Santa J. Ono the University of Cincinnati. Ono has studied on ocular surface inflammation and the immune basis of age-related macular degeneration. His early work focused on the association of certain MHC haplotypes with susceptibility and resistance to type 1 diabetes. Using a number of recombinant and congenic rat strains, the work mapped susceptibility genes in the BB rat to the class II MHC loci. His work also showed that class I and II MHC gene products are expressed at higher levels or de novo on the insulin-producing beta cells of the islets of Langerhans. He focused much of his research in the

pos: Insulin effect of increasing glucose uptake and storage. Finally, insulin is degraded, terminating the response. In mammals, insulin is synthesized in the pancreas within the beta cells. One million to three million pancreatic islets form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion accounts for only 2% of the total mass of the pancreas. Within the pancreatic islets, beta cells constitute 65–80% of all the cells. Insulin consists of two polypeptide chains, the A- and B- chains, linked together by disulfide bonds. It is however first synthesized as a single polypeptide called preproinsulin in

pos: Pancreatic progenitor cell Pancreatic progenitor cell Pancreatic progenitor cells are multipotent stem cells originating from the developing fore-gut endoderm which have the ability to differentiate into the lineage specific progenitors responsible for the developing pancreas. They give rise to both the endocrine and exocrine cells. Exocrine cells constitute the acinar cells and the ductal cells. The endocrine cells constitute the beta cells which make insulin, alpha cells which secrete glucagon, delta cells which secrete somatostatin and the PP-cells which secrete pancreatic polypeptide. Pancreatic progenitor cells have been shown to arise from cells originating from the developing foregut during mammalian development. It has been

pos: Blood sugar level several interacting systems, of which hormone regulation is the most important. There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels: These hormones are secreted from pancreatic islets which are bundles of endocrine tissues. There are four types of pancreatic islets, alpha (A) cells, beta (B) cells, Delta (D) cells and F cells. Glucagon is secreted from alpha cells, while insulin is secreted by beta cells. Together they regulate the blood-glucose levels through negative feedback, a process where the end product of one reaction stimulates the beginning of another reaction. In blood-glucose levels, insulin lowers the concentration

pos: Insulin conflicting influences on insulin release by beta cells, because insulin release is inhibited by α-adrenergic receptors and stimulated by β-adrenergic receptors. The net effect of norepinephrine from sympathetic nerves and epinephrine from adrenal glands on insulin release is inhibition due to dominance of the α-adrenergic receptors. When the glucose level comes down to the usual physiologic value, insulin release from the β-cells slows or stops. If the blood glucose level drops lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from islet of Langerhans alpha cells) forces release of glucose into the blood from

pos: Hyperinsulinemia and disturbances in insulin release. With a reduced response to insulin, the beta cells of the pancreas secrete increasing amounts of insulin in response to the continued high blood glucose levels resulting in hyperinsulinemia. In insulin resistant tissues, a threshold concentration of insulin is reached causing the cells to uptake glucose and therefore decreases blood glucose levels. Studies have shown that the high levels of insulin resulting from insulin resistance might enhance insulin resistance. Studies on mice with genetically reduced circulating insulin suggest that hyperinsulinemia plays a causal role in high fat diet-induced obesity. In this study, mice with reduced

pos: Sweetened beverage II diabetes (T2DM) pathogenesis are insulin resistance and impaired insulin secretion. In the earlier stages of disease development, cells throughout the body become resistant to the effects of insulin. Therefore, insulin is unable to cause cells to take up glucose (among other impairments) and glucose builds up in the blood. As a result, insulin secretion is ramped up, to try to compensate for this lack of response. For a while this may work, but eventually, the body's ability to secrete insulin from the pancreatic beta cells gets burnt out. In later stages of T2DM, patient cells are both resistant to

pos: Pancreatic islets by scarce alpha, delta and PP cells in the periphery, human islets display alpha and beta cells in close relationship with each other throughout the cluster. Islets can influence each other through paracrine and autocrine communication, and beta cells are coupled electrically to six to seven other beta cells (but not to other cell types). The paracrine feedback system of the pancreatic islets has the following structure: A large number of G protein-coupled receptors (GPCRs) regulate the secretion of insulin, glucagon and somatostatin from pancreatic islets, and some of these GPCRs are the targets of drugs used to treat type-2

pos: Insulin the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited. Their neighboring alpha cells, by taking their

pos: Insulin cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. If beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is

pos: Delta cell Delta cell Delta cells (δ-cells or D cells) are somatostatin-producing cells. They can be found in the stomach, intestine and the pancreatic islets. In rodents, delta-cells are located in the periphery of the islets; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well. In both species, the peptide hormone Urocortin3 (Ucn3) is a major local signal that is released from beta cells (and alpha cells in primates) to induce the local secretion of somatostatin. Ghrelin can also strongly stimulate somatostatin secretion, thus indirectly inhibiting insulin release. Viewed under an electron

pos: Glycolysis latter reactions coincide with the halting of glycolysis in the liver. In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of homeostasis. The beta cells in the pancreatic islets are sensitive to the blood glucose concentration. A rise in the blood glucose concentration causes them to release insulin into the blood, which has an effect particularly on the liver, but also on fat and muscle cells, causing these tissues to remove glucose from the blood. When the blood sugar falls the pancreatic beta cells cease insulin production, but, instead, stimulate

pos: Epithelial–mesenchymal transition promoter region. However, later, another set of experiments suggested that labelled β-cells de-differentiate to a mesenchymal-like phenotype "in vitro", but fail to proliferate; thus initiating a debate in 2007. Since these studies in human islets lacked lineage-tracing analysis, these findings from irreversibly tagged beta cells in mice were extrapolated to human islets. Thus, using a dual lentiviral and genetic lineage tracing system to label β-cells, it was convincingly demonstrated that adult human islet β-cells undergo EMT and proliferate "in vitro". Also, these findings were confirmed in human fetal pancreatic insulin-producing cells, and the mesenchymal cells derived from pancreatic islets can

pos: Glutamate dehydrogenase energy by being used in the citric acid cycle to ultimately produce ATP. In microbes, the activity is controlled by the concentration of ammonium and or the like-sized rubidium ion, which binds to an allosteric site on GLDH and changes the K (Michaelis constant) of the enzyme. The control of GLDH through ADP-ribosylation is particularly important in insulin-producing β cells. Beta cells secrete insulin in response to an increase in the ATP:ADP ratio, and, as amino acids are broken down by GLDH into α-ketoglutarate, this ratio rises and more insulin is secreted. SIRT4 is necessary to regulate the metabolism of

pos: Pancreatic islets host rejection of donor islets. An alternative source of beta cells, such insulin-producing cells derived from adult stem cells or progenitor cells would contribute to overcoming the shortage of donor organs for transplantation. The field of regenerative medicine is rapidly evolving and offers great hope for the nearest future. However, type 1 diabetes is the result of the autoimmune destruction of beta cells in the pancreas. Therefore, an effective cure will require a sequential, integrated approach that combines adequate and safe immune interventions with beta cell regenerative approaches. It has also been demonstrated that alpha cells can spontaneously switch fate

pos: Homeostasis many vertebrates, which cools the body also by the evaporation of water, but this time from the mucous membranes of the throat and mouth. Blood sugar levels are regulated within fairly narrow limits. In mammals the primary sensors for this are the beta cells of the pancreatic islets. The beta cells respond to a rise in the blood sugar level by secreting insulin into the blood, and simultaneously inhibiting their neighboring alpha cells from secreting glucagon into the blood. This combination (high blood insulin levels and low glucagon levels) act on effector tissues, chief of which are the liver, fat

pos: Insulin oscillation and CO may be involved. The effect of these neural factors is to induce sudden dramatic elevation of calcium in the cytoplasm by releasing calcium from the endoplasmic reticulum (ER) of the beta cells. This elevation results in release of ATP from the beta cells. The released ATP in turn binds to receptors on neighbouring beta cells leading to a regenerative wave of rapid calcium elevation among the cells within the islet. This signal is believed to entrain pulsatile insulin release from the islets into a common pancreatic rhythm. The insulin oscillations are particularly pronounced in the portal vein delivering

pos: Insulinoma Insulinoma An insulinoma is a tumor of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumor. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumor (PNET) group ("functional" because it increases production of insulin). In the Medical Subject Headings classification, insulinoma is the only subtype of "islet cell adenoma". Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose

pos: Insulin characterized by abnormally high blood glucose concentrations, and generalized body wasting. In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance. Type 2 diabetes is characterized by high rates of glucagon secretion into the

neg: Frederick Banting in the blood which was then excreted in urine. Attempts to extract insulin from ground-up pancreas cells were unsuccessful, likely because of the destruction of the insulin by the proteolysis enzyme of the pancreas. The challenge was to find a way to extract insulin from the pancreas prior to its being destroyed. Moses Barron published an article in 1920 which described experimental closure of the pancreatic duct by ligature; this further influenced Banting's thinking. The procedure caused deterioration of the cells of the pancreas that secrete trypsin which breaks down insulin, but it left the islets of Langerhans intact. Banting

neg: Paul Langerhans Paul Langerhans Paul Langerhans (25 July 1847 – 20 July 1888) was a German pathologist, physiologist and biologist, credited with the discovery of the cells that secrete insulin, named after him as the islets of Langerhans. Langerhans was born in Berlin on 25 July 1847, the son of a physician. He later entered the renowned Graues Kloster in the same city. Due to his outstanding performance he was exempted from the final oral examinations. He began his medical studies at the University of Jena and completed them in Berlin. In February 1869, he presented a thesis entitled “Contributions to the

neg: Enteroendocrine cell somatostatin Gastric enteroendocrine cells are found in the gastric glands, mostly at their base. The G cells secrete gastrin, post-ganglionic fibers of the vagus nerve can release gastrin-releasing peptide during parasympathetic stimulation to stimulate secretion. Enterochromaffin-like cells are enteroendocrine and neuroendocrine cells also known for their similarity to chromaffin cells secreting histamine, which stimulates G cells to secrete gastrin. Other hormones produced include cholecystokinin, somatostatin, vasoactive intestinal peptide, substance P, alpha and gamma-endorphin. Pancreatic enteroendocrine cells are located in the islets of Langerhans and produce most importantly the hormones insulin and glucagon. The autonomous nervous system strongly regulates their secretion,

neg: Insulin signal transduction pathway region called Islets of Langerhans. In the islets of Langerhans, there are beta-cells, which are responsible for production and storage of insulin. Insulin is secreted as a response mechanism for counteracting the increasing excess amounts of glucose in the blood. Glucose in the body increases after food consumption. This is primarily due to carbohydrate intake, but to a much lesser degree protein intake ()(). Depending on the tissue type, the glucose enters the cell through facilitated or passive diffusion. In muscle and adipose tissue, glucose enters through GLUT 4 receptors via facilitated diffusion (). In brain, kidney and retina, glucose

neg: History of diabetes further clarified in 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs. The islets of Langerhans was discovered in 1869 by an anatomist named Paul Langerhans. He identified the keys cells in the pancreas which produce the main substance that controls glucose levels in the body. Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at

neg: Sulfatide islet of Langerhans and in rat β TC3 cells. Research has shown that in the pancreases of Type II diabetic mouse models, there is a deficiency of C16:0. Additional research has shown that C16:0 plays an important role in assisting to improve insulin crystal preservation, and as the β cells in the pancreas secrete insulin, sulfatide aids in the monomerization of insulin, which is the breakdown of insulin into its basics components or monomers. Consequently, sulfatide is needed in order to maintain normal insulin secretion, which sulfatide is capable of mediating through stimulation of calcium dependent exocytosis and adenosine triphosphate

neg: Epsilon cell pancreatic polypeptide was evident sporadically. Epsilon cell Epsilon cells (ε-cells) are endocrine cells found in the Islets of Langerhans and produce the hormone ghrelin. They were discovered in mice. In human fetal pancreases, single epsilon cells scattered in primitive exocrine tissue were observed to start aggregating into clusters after gestational week 13. From gestational week 21, epsilon cells were observed around developing islets, forming an almost continuous layer at the rim of the islets. In adult pancreas samples, they remained localized on the mantle of the islets in different amounts. Production of ghrelin with insulin, glucagon, or somatostatin was not

neg: Epsilon cell Epsilon cell Epsilon cells (ε-cells) are endocrine cells found in the Islets of Langerhans and produce the hormone ghrelin. They were discovered in mice. In human fetal pancreases, single epsilon cells scattered in primitive exocrine tissue were observed to start aggregating into clusters after gestational week 13. From gestational week 21, epsilon cells were observed around developing islets, forming an almost continuous layer at the rim of the islets. In adult pancreas samples, they remained localized on the mantle of the islets in different amounts. Production of ghrelin with insulin, glucagon, or somatostatin was not detected during development. Co-production with

neg: Nanopore example, rat pancreatic cells are microencapsulated, they receive nutrients and release insulin through nanopores being totally isolated from their neighboring environment i.e. foreign cells. This knowledge can help to replace nonfunctional islets of Langerhans cells in the pancreas (responsible for producing insulin), by harvested piglet cells. They can be implanted underneath the human skin without the need of immunosuppressants which put diabetic patients at a risk of infection. Nanopore A nanopore is a pore of nanometer size. It may, for example, be created by a pore-forming protein or as a hole in synthetic materials such as silicon or graphene. When

neg: Downregulation and upregulation reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell's sensitivity to the elevated hormone concentration. This process is illustrated by the insulin receptor sites on target cells in a person with type 2 diabetes. Due to the elevated levels of blood glucose in an overweight individual, the β-cells (islets of Langerhans) in the pancreas must release more insulin than normal to meet the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin

neg: Insulin resistance this compensatory increase does not occur, blood glucose concentrations increase and type 2 diabetes or latent autoimmune diabetes of adults occurs. Any food or drink containing glucose (or the digestible carbohydrates that contain it, such as sucrose, starch, etc.) causes blood glucose levels to increase. In normal metabolism, the elevated blood glucose level instructs beta (β) cells in the Islets of Langerhans, located in the pancreas, to release insulin into the blood. The insulin, in turn, makes insulin-sensitive tissues in the body (primarily skeletal muscle cells, adipose tissue, and liver) absorb glucose, and thereby lower the blood glucose level. The

neg: Essential hypertension syndrome. Insulin is a polypeptide hormone secreted by cells in the islets of Langerhans, which are contained throughout the pancreas. Its main purpose is to regulate the levels of glucose in the body antagonistically with glucagon through negative feedback loops. Insulin also exhibits vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic activity without elevating mean arterial pressure. However, in more extreme conditions such as that of the metabolic syndrome, the increased sympathetic neural activity may over-ride the vasodilatory effects of insulin. Recent studies claim that obesity is a risk factor for hypertension because of activation of the renin–angiotensin system

neg: Insulin it is reduced to fragments, whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered orally or sublingually. In 1869, while studying the structure of the pancreas under a microscope, Paul Langerhans, a medical student in Berlin, identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas. The function of the "little heaps of cells", later known as the "islets of Langerhans", initially remained unknown, but Édouard Laguesse later suggested they might produce secretions that play a regulatory role in digestion. Paul

neg: Frederick Banting realized that this procedure would destroy the trypsin-secreting cells but not the insulin. Once the trypsin-secreting cells had died, insulin could be extracted from the islets of Langerhans. Banting discussed this approach with J. J. R. Macleod, Professor of Physiology at the University of Toronto. Macleod provided experimental facilities and the assistance of one of his students, Charles Best. Banting and Best, with the assistance of biochemist James Collip, began the production of insulin by this means. As the experiments proceeded, the required quantities could no longer be obtained by performing surgery on living dogs. In November 1921, Banting hit

neg: Insulin signal transduction pathway enters passively. In the beta-cells of the pancreas, glucose enters through the GLUT 2 receptors (process described below). Insulin biosynthesis is regulated by transcriptional and translational levels. The β-cells promote their protein transcription in response to nutrients. The exposure of rat Langerhans islets to glucose for 1 hour is able to remarkably induce the intracellular proinsulin levels. It was noted that the proinsulin mRNA remained stable. This suggests that the acute response to glucose of the insulin synthesis is independent of mRNA synthesis in the first 45 minutes, because the blockage of the transcription decelerated the insulin accumulation during that

neg: Development of the endocrine system islets cells are unable to sufficiently produce cAMP and rapidly degrade cAMP by phosphodiesterase necessary to secrete glucagon and insulin. During fetal development, the storage of glycogen is controlled by fetal glucocorticoids and placental lactogen. Fetal insulin is responsible for increasing glucose uptake and lipogenesis during the stages leading up to birth. Fetal cells contain a higher amount of insulin receptors in comparison to adults cells and fetal insulin receptors are not downregulated in cases of hyperinsulinemia. In comparison, fetal haptic glucagon receptors are lowered in comparison to adult cells and the glycemic effect of glucagon is blunted. This temporary

neg: Peter Gruss A study of the pancreas which he conducted enabled him to detect genes involved in the development of insulin-producing islets of Langerhans. This also provided the basis for differentiating stem cells in insulin-producing cells. Upon taking office, Gruss was regarded by the press as an "American-style man of action" and an "unassuming high flyer". In his inaugural speech, Gruss focused on the financial scope for science: he called for the introduction of a collective bargaining law specifically for the field of science to enable Germany to attract the world's best scientists. He also spoke out in favour of a reliable

neg: AMP-activated protein kinase the liver by phosphorylation. AMPK also phosphorylates and inactivates 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme in cholesterol synthesis. HMGR converts 3-hydroxy-3-methylglutaryl-CoA, which is made from acetyl-CoA, into mevalonic acid, which then travels down several more metabolic steps to become cholesterol. AMPK, therefore, helps regulate fatty acid oxidation and cholesterol synthesis. Insulin is a hormone which helps regulate glucose levels in the body. When blood glucose is high, insulin is released from the Islets of Langerhans. Insulin, among other things, will then facilitate the uptake of glucose into cells via increased expression and translocation of glucose transporter GLUT-4. Under conditions of

neg: Lipid signaling syndrome. Experimental evidence shows that there is substantial increase of ceramide levels upon adding palmitate. Ceramide accumulation activates PP2A and the subsequent dephosphorylation and inactivation of AKT, a crucial mediator in metabolic control and insulin signaling. This results in a substantial decrease in insulin responsiveness (i.e. to glucose) and in the death of insulin-producing cells in the pancreas called islets of Langerhans. Inhibition of ceramide synthesis in mice via drug treatments or gene-knockout techniques prevented insulin resistance induced by fatty acids, glucocorticoids or obesity. An increase in "in vitro" activity of acid SMase has been observed after applying multiple stress

neg: Glucagon activates the former and inhibits the latter. This regulates the reaction catalyzing fructose-2,6-bisphosphate (a potent activator of phosphofructokinase-1, the enzyme that is the primary regulatory step of glycolysis) by slowing the rate of its formation, thereby inhibiting the flux of the glycolysis pathway and allowing gluconeogenesis to predominate. This process is reversible in the absence of glucagon (and thus, the presence of insulin). Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase in hepatocytes. The hormone is synthesized and secreted from alpha cells (α-cells) of the islets of Langerhans, which are located in the endocrine portion of the

neg: Glucagon-like peptide-1 induction and inhibited by insulin. Conversely, intestinal proglucagon gene expression is reduced during fasting and stimulated upon food consumption. In mammals, the transcription gives rise to identical mRNA in all three cell types, which is further translated to the 180 amino acid precursor called proglucagon. However, as a result of tissue-specific posttranslational processing mechanisms, different peptides are produced in the different cells. In the pancreas (α-cells of the islets of Langerhans), proglucagon is cleaved by prohormone convertase (PC) 2 producing glicentin-related pancreatic peptide (GRPP), glucagon, intervening peptide-1 (IP-1) and major proglucagon fragment (MPGF). In the gut and brain, proglucagon is

neg: Johanson–Blizzard syndrome pancreas occurs with JBS, though it is sometimes less common and less pronounced than the more prominent effects on exocrine function. The islets of Langerhans are ducts in the pancreas where endocrine activity such as the release of hormones glucagon, somatostatin and insulin takes place. Pancreatic endocrine insufficiency in JBS can be associated with either a buildup of connective tissue in the islet regions, congenital replacement of the islets with fatty tissue, or improper nerve signalling to the islets. Endocrine dysfunction of the pancreas often results in diabetes mellitus. Both insulin resistance and diabetes have been observed with JBS, and

neg: Pancreatic islets Pancreatic islets The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1 to 2% of the pancreas volume and receive 10–15% of its blood flow. The pancreatic islets are arranged in density routes throughout the human pancreas, and are important in the metabolism of glucose. There are about 3 million islets distributed in the form of "density routes" throughout the pancreas of a healthy adult human, each of which measures an average of about 0.1 mm (109

neg: Glucagon-like peptide-1 GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to increase GLP-1 activity. As opposed to common treatment agents such as insulin and sulphonylurea, GLP-1-based treatment has been associated with weight loss and a lower risk of hypoglycemia, two important considerations for patients with type 2 diabetes. The proglucagon gene is expressed in several organs including the pancreas (α-cells of the islets of Langerhans), gut (intestinal enteroendocrine L-cells) and brain (caudal brainstem and hypothalamus). Pancreatic proglucagon gene expression is promoted upon fasting and hypoglycaemia

neg: Langhans giant cell derived (like Langhans cells) from monocytes and named after Paul Langerhans. (The Islets of Langerhans are also named after Paul Langerhans.) In 2012, a research paper showed that when activated CD4+ T cells and monocytes are in close contact, interaction of CD40-CD40L between these two cells and subsequent IFNγ secretion by the T cells causes upregulation and secretion of fusion-related molecule DC-STAMP (dendritic cell-specific transmembrane protein) by the monocytes, which results in LGC formation. Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis. Langhans giant cell Langhans giant cells (also known

neg: Insulin Langerhans' son, Archibald, also helped to understand this regulatory role. The term "insulin" originates from "insula", the Latin word for islet/island. In 1889, the physician Oskar Minkowski, in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine, they found sugar, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by the American physician and scientist Eugene Lindsay Opie, when he isolated the role of the pancreas to the islets of Langerhans: "Diabetes mellitus when the result

neg: Lifestyle causes of diabetes mellitus type 2 that "produce fewer and smaller mitochondria than is normal," and are thus prone to insulin resistance. Fat tissue has also been shown to be involved in managing much of the body's response to insulin and control of uptake of sugar. It secretes RBP4 which increases insulin resistance by blocking the action of insulin in muscle and liver. Fat cells also secrete adiponectin which acts in an opposite way to RBP4 by improving the action of insulin, however, engorged fat cells secrete it in lower amount than normal fat cells. The obese therefore may have higher level of RBP4 but lower

neg: John Leonora to have an activity indistinguishable from the isolated parotid hormone or the gene-expressed hormone. Meanwhile, it was discovered that the acinar cells of the parotid glands were apparently the source of the parotid hormone. Preliminary research suggested the parotid hormone not only regulates dental structures but also influences insulin secretion by the pancreas. These systemic effects have yet to be followed up. As Leonora stated in an undated letter, "I anticipate finding receptors [for the parotid hormone] in the odontoblasts in teeth, osteocytes in bone matrix, Islets of Langerhans…" John Leonora John Leonora (January 30, 1928 - February 17, 2006)

neg: Insulin-like growth factor example, only one insulin-like receptor exists in the nematode "C. elegans". Additionally, "C. elegans" do not have specialized organs such as the (Islets of Langerhans), which sense insulin in response to glucose homeostasis. Moreover, IGF1 affects lifespan in nematodes by causing dauer formation, a developmental stage of C. elegans larva. There is no mammalian correlate. Therefore, it is an open question as to whether either IGF-1 or insulin in the mammal may perturb aging, although there is the suggestion that dietary restriction phenomena may be related. Other studies are beginning to uncover the important role the IGFs play in diseases

neg: Lydia Maria Adams DeWitt in different species. While at the St. Louis Department of Health, she conducted extensive research on diphtheria and diagnosis of typhoid. Her work on isolating the islets of Langerhans cells from the pancreas and her discovery that they secreted a substance involved in carbohydrate metabolism set the stage for the discovery of insulin and its role in diabetes by a Canadian team of researchers. At the University of Chicago, DeWitt and her team worked on developing a drug to treat tuberculosis based on the work of Paul Ehrlich, who developed a treatment for syphilis by chemically modifying a dye that

neg: Diabetic ketoacidosis a total body water shortage of about 6 liters (or 100 mL/kg), in addition to substantial shortages in sodium, potassium, chloride, phosphate, magnesium and calcium. Glucose levels usually exceed 13.8 mmol/L or 250 mg/dL. DKA is common in type 1 diabetes as this form of diabetes is associated with an absolute lack of insulin production by the islets of Langerhans. In type 2 diabetes, insulin production is present but is insufficient to meet the body's requirements as a result of end-organ insulin resistance. Usually, these amounts of insulin are sufficient to suppress ketogenesis. If DKA occurs in someone with type

neg: Pancreas These supply the head of the pancreas. The body and neck of the pancreas drain into the splenic vein; the head drains into the superior mesenteric and portal veins. The pancreas contains tissue with an endocrine and exocrine role, and this division is also visible when the pancreas is viewed under a microscope. The tissues with an endocrine role can be seen under staining as lightly-stained clusters of cells, called pancreatic islets (also called islets of Langerhans). Darker-staining cells form clusters called acini, which are arranged in lobes separated by a thin fibrous barrier. The secretory cells of each acinus

neg: Glucose uptake phosphorylates GLUT4, thereby increasing its sensitivity to insulin. During fasting, some GLUT4 transporters will be expressed at the surface of the cell. However, most will be found in cytoplasmic vesicles within the cell. After a meal and at the binding of insulin (released from the islets of Langerhans) to receptors on the cell surface, a signalling cascade begins by activating phosphatidylinositolkinase activity which culminates in the movement of the cytoplasmic vesicles toward the cell surface membrane. Upon reaching the plasmalemma, the vesicles fuse with the membrane, increasing the number of GLUT4 transporters expressed at the cell surface, and hence increasing

neg: History of diabetes a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards. In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin "insula", meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas. The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was

neg: Insulin concluded that the digestive secretions that Minkowski had originally studied were breaking down the islet secretion, thereby making it impossible to extract successfully. A surgeon by training, Banting knew certain arteries could be tied off that would lead most of the pancreas to atrophy, while leaving the islets of Langerhans intact. He reasoned that a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. He jotted a note to himself: "Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of

neg: Pancreas glucagon to increase the levels of glucose, and insulin to decrease it. The islets are crisscrossed by a dense network of capillaries. The capillaries of the islets are lined by layers of islet cells, and most endocrine cells are in direct contact with blood vessels, either by cytoplasmic processes or by direct apposition. The islets function independently from the digestive role played by the majority of pancreatic cells. Activity of the cells in the islets is affected by the autonomic nervous system: The pancreas plays a vital role in the digestive system. It secretes a fluid that contains enzymes into

neg: Diabetes management A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to sensed glucose. When islet cells have been transplanted via the Edmonton protocol, insulin production (and glycemic control) was restored, but at the expense of continued immunosuppression drugs. Encapsulation of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant. Research is being done at several locations in which islet cells

neg: Hepoxilin activity of their precursor hepoxilins. Based on these studies, it has been proposed that the hepoxilins and trioxilins function in human physiology and pathology by, for example, promoting inflammation responses and dilating arteries to regulate regional blood flow and blood pressure. HxA3 and HxB3 were first identified, named, shown to have biological activity in stimulating insulin secretion in cultured rat pancreatic islets of Langerhans in Canada in 1984 by CR Pace-Asciak and JM Martin. Shortly thereafter, Pace-Asciak identified, named, and showed to have insulin secretagogue activity HxA4 and HxB4. HxA3, HxB3, and their isomers are distinguished from most other eicosanoids

neg: Gamma-Aminobutyric acid neurites and the formation of synapses. GABA also regulates the growth of embryonic and neural stem cells. GABA can inﬂuence the development of neural progenitor cells via brain-derived neurotrophic factor (BDNF) expression. GABA activates the GABA receptor, causing cell cycle arrest in the S-phase, limiting growth. Besides the nervous system, GABA is also produced at relatively high levels in the insulin-producing β-cells of the pancreas. The β-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring islet α-cells and inhibits them from secreting glucagon (which would counteract insulin’s effects). GABA can promote the replication

neg: HES1 endocrine cell types that will form the islets of Langerhans. The absence of "Hes1" in the developing intestine of mice promotes the increase of Math1 (a protein required for the production of intestinal secretory cell types), which leads to an increase of goblet, enteroendocrine, and Paneth cells. When "Hes1" is deleted in mouse and zebrafish, surplus goblet cells and enteroendocrine cells are made while few enterocytes are made. Liver progenitor cells differentiate into two different cell types: hepatocytes and biliary epithelial cells. When "Hes1" expression is low, hepatocytes form normally, but bile ducts are completely absent. This phenotype resembles Alagille

neg: Latent autoimmune diabetes in adults a low C-peptide and raised antibodies against the islets of Langerhans support the diagnosis. It can only be treated with the usual oral treatments for type 2 diabetes for a certain period of time, after which insulin treatment is usually necessary, as well as long-term monitoring for complications. The concept of LADA was first introduced in 1993, though The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus does not recognize the term, instead including it under the standard definition of diabetes mellitus type 1. The symptoms of latent autoimmune diabetes in adults are similar to those of other

neg: ISL1 ISL1 Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the "isl1" gene. This gene encodes a transcription factor containing two N-terminal LIM domains and one C-terminal homeodomain. The encoded protein plays an important role in the embryogenesis of pancreatic islets of Langerhans. In mouse embryos, a deficiency of this gene fail to undergo neural tube motor neuron differentiation. ISL1 has been shown to interact with Estrogen receptor alpha. ISL1 is a marker for cardiac progenitors of the secondary heart field (SHF) which includes the right ventricle and the outflow tract. It also has a

neg: PDX1 the initial pancreatic buds, which further proliferate and branch in response to FGF-10 signaling. Afterwards, fating of the pancreatic cells begins; a population of cells has Notch signaling inhibited, and subsequently, expresses Ngn3. This Ngn3 population is a transient population of pancreatic endocrine progenitors that gives rise to the α, β, Δ, PP, and ε cells of the islets of Langerhans. Other cells will give rise to the exocrine and ductal pancreatic cell populations. Pdx1 is necessary for the development of the proximal duodenum and maintenance of the gastro-duodenal junction. Duodenal enterocytes, Brunner's glands and entero-endocrine cells (including those in

neg: Glucose major facilitator superfamily. In the small intestine (more precisely, in the jejunum), glucose is taken up into the intestinal epithelial cells with the help of glucose transporters via a secondary active transport mechanism called sodium ion-glucose symport via the sodium/glucose cotransporter 1. The further transfer occurs on the basolateral side of the intestinal epithelial cells via the glucose transporter GLUT2, as well as their uptake into liver cells, kidney cells, cells of the islets of Langerhans, nerve cells, astrocytes and tanyocytes. Glucose enters the liver via the vena portae and is stored there as a cellular glycogen. In the liver

neg: ALOX12 these studies, it is usually unclear which, if any metabolite(s) of "Alox12" was implicated. The metabolic syndrome is a clustering of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose (or overt diabetes), high serum triglycerides, and low high-density lipoprotein (HDL) levels. ALOX12 and its metabolite, 12("S")-HETE, are elevated in the islets of Langerhans of patients with type 1 diabetes or type 2 diabetes as well as in the fat cells of white adipose tissue of morbidly obese type 2 diabetic patients. The PP cells (i.e. gamma cells) of

neg: NH41 NH41 The NR4A1 gene is a transcription factor important in the development of cells that secrete the hormone insulin-like 3 (INSL3). In general, the NR4A gene family regulates cell growth and differentiation. In humans, INSL3 aids in the regulation of testicular descent during fetal development. In an adult INSL3 helps in keeping germ cells alive, in both males and females. In the male reproductive system the NR4A1 gene is a promoter of insulin-like 3 in Leydig cells. Leydig cells are located in the testis and known for the function as a support cell in spermatogenesis. Along with other things they

neg: Artificial cell A drawback of the technique is that encapsulating a cell decreases its viability and ability to proliferate and differentiate. Further, after some time within the microcapsule, cells form clusters that inhibit the exchange of oxygen and metabolic waste, leading to apoptosis and necrosis thus limiting the efficacy of the cells and activating the host's immune system. Artificial cells have been successful for transplanting a number of cells including islets of Langerhans for diabetes treatment, parathyroid cells and adrenal cortex cells. Shortage of organ donors make artificial cells key players in alternative therapies for liver failure. The use of artificial cells

neg: Hepoxilin in the perception of pain caused by exogenous and endogenous physical and chemical stimuli in a wide range of animal species including humans. Cultured rat RINm5F pancreatic islet cells undergoing oxidative stress secrete HxB3; HxB3 (and HxA3) in turn upregulates peroxidase enzymes which act to decrease this stress; it is proposed that this HxB3-triggered induction of oxidases constitutes a general compensatory defense response used by a variety of cells to protect their vitality and functionality. The insulin-secreting actions of HxA3 and HxB3 on isolate rat pancreatic islet cells involves their ability to increase or potentiate the insulin-secreting activity of glucose,

neg: Preputial mucosa These cells secrete cytokines (a non-antibody protein that generates an immune response on contact with specific antigens), and are an essential part of the immune system. Fleiss "et al". (1998) point out that Weiss "et al". (1993) studied foreskins of neonates and their findings may not be applicable to adults. De Witte "et al". (2007) report that Langerhans cells produce Langerin. Langerin inhibits the infection of T-cells with HIV-1. Dinh "et al". (2012) compared the depth of the keratin layer of the inner foreskin with the depth of the keratin layer outer foreskin in foreskins of healthy Ugandan males who