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Regulation Of Insulin Secretion

Insulin

Insulin

This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] 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.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>

Regulation Of Insulin Secretion: The Role Of Second Messengers

Regulation Of Insulin Secretion: The Role Of Second Messengers

Summary This review summarises briefly studies performed in the last 5–6 years concerning the role of second messengers in the regulation of insulin secretion, using intact and electrically permeabilized rat islets of Langerhans. It is concluded that cyclic AMP (through protein kinase A), calcium (through calcium-calmodulin dependent protein kinases) and diacylglycerol (through protein kinase C) may be important second messengers in modulating the effects of specific secretagogues on insulin release. However, recent studies strongly suggest that neither protein kinase A nor protein kinase C are directly involved in the regulation of insulin secretion by glucose. The possible involvement of other second messengers, nitric oxide and arachidonic acid, in the regulation of secretion is also briefly reviewed. Continue reading >>

Regulation Of Insulin Secretion

Regulation Of Insulin Secretion

Biological Process Any process that modulates the frequency, rate or extent of the regulated release of insulin. This table lists all terms that are direct descendants (child terms) of GO:0050796 Child Term Relationship to GO:0050796 GO:0046676 negative regulation of insulin secretion is_a GO:0032024 positive regulation of insulin secretion is_a GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus is_a The GO editorial group is intending to improve the information provided in this area of the GO. If you would like to be involved in discussions regarding this development activity, please email the GO Consortium. Please note that it is still appropriate to use this term for curation or analysis purpose: Ontology Development Project signalling Link Database ID Description InterPro IPR028691 Synaptotagmin-9 InterPro IPR030796 Islet cell autoantigen 1 InterPro IPR033630 Homeobox protein NKX-6.1 These tables show the number of times the term listed in the table has been co-annotated. The top 100 of 1,611 co-occurring terms Co-occurring Term PR S% #Together #Compared GO:0050796 regulation of insulin secretion 48,516.09 100.00 1,457 1,457 GO:0030667 secretory granule membrane 13,044.95 11.21 235 874 GO:0017158 regulation of calcium ion-dependent exocytosis 8,874.90 9.82 255 1,394 GO:0003309 type B pancreatic cell differentiation 21,289.15 8.94 147 335 GO:0042593 glucose homeostasis 5,708.73 8.58 351 2,983 GO:0060559 positive regulation of calcidiol 1-monooxygenase activity 48,062.68 7.27 106 107 GO:0051044 positive regulation of membrane protein ectodomain proteolysis 12,630.71 6.08 107 411 GO:0031018 endocrine pancreas development 6,465.71 5.89 139 1,043 GO:0060557 positive regulation of vitamin D biosynthetic process 48,516.10 5.56 81 8 Continue reading >>

Regulation Of Insulin Secretion

Regulation Of Insulin Secretion

This activity is intended for endocrinologists, diabetologists, family physicians, and primary care physicians. The goal of the conference coverage from the 62nd Scientific Sessions of the American Diabetes Association is to provide clinicians with the most current information on the basic science of diabetes and how this science informs the treatment of the disease. By presenting cutting-edge advances in the study of diabetes, conferences summaries aim to encourage the evaluation of current practice methods and to support clinicians who treat patients with diabetes and its ensuing complications. Upon completion of this activity, participants should be able to: Discuss new findings on the hormonal, metabolic, and neural aspects of insulin and leptin signaling in the hypothalamus. Discuss the progress that has been made in the understanding of the molecular mechanisms of insulin secretion and the therapeutic strategies that these findings suggest. Assistant Professor and Deputy Chief, Section of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, Texas. Disclosure: Arun S. Rajan, MD, has no significant financial interests to disclose. Medical Education Collaborative, a nonprofit education organization, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Medical Education Collaborative designates this educational activityfor a maximum of 1 category 1 credits toward the AMA Physician'sRecognition Award. Each physician should claim only those credits thathe/she actually spent in the activity. This CME activity is cosponsored by Medical EducationCollaborative and Medscape, also an ACCME-accredited provider. For questions regarding the content of this activity, con Continue reading >>

Optogenetic Regulation Of Insulin Secretion In Pancreatic Β-cells

Optogenetic Regulation Of Insulin Secretion In Pancreatic Β-cells

Pancreatic β-cell insulin production is orchestrated by a complex circuitry involving intracellular elements including cyclic AMP (cAMP). Tackling aberrations in glucose-stimulated insulin release such as in diabetes with pharmacological agents, which boost the secretory capacity of β-cells, is linked to adverse side effects. We hypothesized that a photoactivatable adenylyl cyclase (PAC) can be employed to modulate cAMP in β-cells with light thereby enhancing insulin secretion. To that end, the PAC gene from Beggiatoa (bPAC) was delivered to β-cells. A cAMP increase was noted within 5 minutes of photostimulation and a significant drop at 12 minutes post-illumination. The concomitant augmented insulin secretion was comparable to that from β-cells treated with secretagogues. Greater insulin release was also observed over repeated cycles of photoinduction without adverse effects on viability and proliferation. Furthermore, the expression and activation of bPAC increased cAMP and insulin secretion in murine islets and in β-cell pseudoislets, which displayed a more pronounced light-triggered hormone secretion compared to that of β-cell monolayers. Calcium channel blocking curtailed the enhanced insulin response due to bPAC activity. This optogenetic system with modulation of cAMP and insulin release can be employed for the study of β-cell function and for enabling new therapeutic modalities for diabetes. Precise control of complex cellular functions with external stimuli is essential for engineering effective cell therapeutics. Pharmacological manipulations typically exhibit poor cellular specificity and temporal control that is not harmonized with the timescale of relevant physiological processes. One such function is the glucose-stimulated insulin secretion (GSIS) Continue reading >>

Regulation Of Insulin Secretion In Human Pancreatic Islets

Regulation Of Insulin Secretion In Human Pancreatic Islets

Regulation of Insulin Secretion in Human Pancreatic Islets Vol. 75:155-179 (Volume publication date February 2013) First published online as a Review in Advance on September 4, 2012 1Oxford Center for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom; email: [emailprotected] 2Alberta Diabetes Institute, University of Alberta, Edmonton T6G 2E1, Canada Pancreatic cells secrete insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient insulin secretion results in diabetes mellitus. The cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse cells and the cell's role in insulin secretion have been extensively investigated. More recently, similar studies have been performed on human cells. These studies have revealed numerous and important differences between human and rodent cells. Here we discuss the properties of human pancreatic cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytotic release of insulin, the cellular control of exocytosis, and the modulation of insulin secretion by circulating hormones and locally released neurotransmitters. Finally, we consider the pathophysiology of insulin secretion and the interactions between genetics and environmental factors that may explain the current diabetes epidemic. Continue reading >>

Normal Regulation Of Blood Glucose

Normal Regulation Of Blood Glucose

The human body wants blood glucose (blood sugar) maintained in a very narrow range. Insulin and glucagon are the hormones which make this happen. Both insulin and glucagon are secreted from the pancreas, and thus are referred to as pancreatic endocrine hormones. The picture on the left shows the intimate relationship both insulin and glucagon have to each other. Note that the pancreas serves as the central player in this scheme. It is the production of insulin and glucagon by the pancreas which ultimately determines if a patient has diabetes, hypoglycemia, or some other sugar problem. In this Article Insulin Basics: How Insulin Helps Control Blood Glucose Levels Insulin and glucagon are hormones secreted by islet cells within the pancreas. They are both secreted in response to blood sugar levels, but in opposite fashion! Insulin is normally secreted by the beta cells (a type of islet cell) of the pancreas. The stimulus for insulin secretion is a HIGH blood glucose...it's as simple as that! Although there is always a low level of insulin secreted by the pancreas, the amount secreted into the blood increases as the blood glucose rises. Similarly, as blood glucose falls, the amount of insulin secreted by the pancreatic islets goes down. As can be seen in the picture, insulin has an effect on a number of cells, including muscle, red blood cells, and fat cells. In response to insulin, these cells absorb glucose out of the blood, having the net effect of lowering the high blood glucose levels into the normal range. Glucagon is secreted by the alpha cells of the pancreatic islets in much the same manner as insulin...except in the opposite direction. If blood glucose is high, then no glucagon is secreted. When blood glucose goes LOW, however, (such as between meals, and during Continue reading >>

Minireview: Intraislet Regulation Of Insulin Secretion In Humans

Minireview: Intraislet Regulation Of Insulin Secretion In Humans

The proper control of blood glucose levels requires the concerted activity of cells within the islets of Langerhans, small (∼50–500 μm) hormone-releasing micro-organs that are diffusely scattered throughout the pancreatic parenchyma. Dysregulation of insulin and glucagon secretion, together with increased peripheral resistance to circulating insulin, is a characteristic feature of the glucose intolerance associated with type 2 diabetes mellitus (T2DM), a disease state currently affecting approximately 8% of the adult population worldwide (1). Whereas the mechanisms controlling insulin secretion at the level of the single β-cell are well studied (2), whether and how single cells within an islet cooperate during activated insulin secretion is less well characterized, especially in human islets. Because phylogenetic differences exist in islet architecture and composition, as well as paracrine and autocrine regulation of cell function, the intraislet mechanisms that regulate insulin secretion may provide an enigmatic route through which the diabetogenic milieu contributes to T2DM. Focusing on studies in human islets, the aim of this minireview is to provide a synopsis of the structural and functional cell-cell signaling processes underlying insulin secretion in man. Within individual β-cells, rising glucose levels enhance glycolytic and citrate cycle flux to increase the cytoplasmic ratio of ATP:ADP (3, 4); alternative fates for glucose (eg, anaerobic production of lactate) are suppressed (5, 6). This, in turn, leads to the closure of hyperpolarizing ATP-sensitive potassium (K+) channels (KATP) through binding of the pore-forming Kir6.2 subunits that, along with the regulatory, SUR1 subunits, form the characteristic octameric channel structure (4, 7, 8). The resultan Continue reading >>

Regulation Of Insulin Secretion In Human Pancreatic Islets.

Regulation Of Insulin Secretion In Human Pancreatic Islets.

Abstract Pancreatic β cells secrete insulin, the body's only hormone capable of lowering plasma glucose levels. Impaired or insufficient insulin secretion results in diabetes mellitus. The β cell is electrically excitable; in response to an elevation of glucose, it depolarizes and starts generating action potentials. The electrophysiology of mouse β cells and the cell's role in insulin secretion have been extensively investigated. More recently, similar studies have been performed on human β cells. These studies have revealed numerous and important differences between human and rodent β cells. Here we discuss the properties of human pancreatic β cells: their glucose sensing, the ion channel complement underlying glucose-induced electrical activity that culminates in exocytotic release of insulin, the cellular control of exocytosis, and the modulation of insulin secretion by circulating hormones and locally released neurotransmitters. Finally, we consider the pathophysiology of insulin secretion and the interactions between genetics and environmental factors that may explain the current diabetes epidemic. Continue reading >>

Regulation Of Insulin Synthesis And Secretion And Pancreatic Beta-cell Dysfunction In Diabetes

Regulation Of Insulin Synthesis And Secretion And Pancreatic Beta-cell Dysfunction In Diabetes

Go to: INSULIN Insulin structure The crystal structure of insulin is well documented as well as the structural features that confer receptor binding affinity and activity. This has been extensively reviewed and readers are encouraged to visit [1] and [2] for excellent discussions on insulin structure and structure-activity relationships. As discussed in this review, insulin receptor downstream signaling intersects with the signaling pathways of other growth factors, including IGF1 and IGF2 [3]. This demonstrates the importance of identifying receptor ligand agonists as potential insulin-mimetic therapeutic agents in diabetes. This section of the review will focus on the native structure of insulin. For an excellent review on the insulin receptor structure and binding domains, readers are encouraged to visit several references [2, 3]. The 3-D structure of monomeric insulin was first discovered by x-ray crystallography and reported in 1926 [4]. More than 40 years later, the structure of the zinc-containing hexameric insulin was solved [5–8]. 2D NMR studies have also contributed to knowledge on the monomeric, dimeric and hexameric conformations of insulin, all revealing information on the native structure of insulin and the amino acids that confer binding specificity to the insulin receptor [1]. Insulin concentration and surrounding pH influence the conformational state of insulin. The monomers tend to form dimers as the concentration of insulin rises, and in the presence of zinc and favorable pH (10 mM Zn++, pH ~6.0) the monomers assemble into higher order conformations called hexamers [9]. As discussed below, interactions among hydrophobic amino acids in insulin dimer structures favor aggregation as concentrations rise. Once the hexamers are secreted from the β-cell a Continue reading >>

Regulation Of Insulin Secretion And Β-cell Mass By Activating Signal Cointegrator 2†

Regulation Of Insulin Secretion And Β-cell Mass By Activating Signal Cointegrator 2†

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes. Continue reading >>

A Role For Glutamate Transporters In The Regulation Of Insulin Secretion

A Role For Glutamate Transporters In The Regulation Of Insulin Secretion

Abstract In the brain, glutamate is an extracellular transmitter that mediates cell-to-cell communication. Prior to synaptic release it is pumped into vesicles by vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor responses after release, glutamate is taken up into glial cells or neurons by excitatory amino acid transporters (EAATs). In the pancreatic islets of Langerhans, glutamate is proposed to act as an intracellular messenger, regulating insulin secretion from β-cells, but the mechanisms involved are unknown. By immunogold cytochemistry we show that insulin containing secretory granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of glutamate in these granules are low, indicating the presence of a protein that can transport glutamate out of the granules. Surprisingly, in β-cells the glutamate transporter EAAT2 is located, not in the plasma membrane as it is in brain cells, but exclusively in insulin-containing secretory granules, together with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory granules is higher than in wild type mice. These data imply a glutamate cycle in which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2. Perturbing this cycle by knocking down EAAT2 expression with a small interfering RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly reduced the rate of granule exocytosis. Simulations of granule energetics suggest that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules and thereby regulate insulin secretion. These data suggest that insulin secretion from β-cells is modulated by the flux of glutamate through the secretory granules. Figures Citation: Gammelsaeter R, Coppola T, Marcaggi P, Storm-M Continue reading >>

Regulation Of Insulin Secretion Pathway Bioinformatics

Regulation Of Insulin Secretion Pathway Bioinformatics

Insulin is a peptide hormone that is responsible for helping with the regulation of carbohydrate and fat metabolism, as it causes the cells of various tissues to absorb glucose in various forms from the bloodstream. Insulin is produced in the beta cells of the islets of Langerhans located in the pancreas, and is ready to be released into the body once it is cleaved from its signal peptide. Once glucose enters the body, it migrates to the pancreas an enters the beta cell, which leads to membrane depolarization and opens the calcium channels, allowing calcium to flow into the cell. The increase of calcium inside the cell initiates the secretion of insulin through secretory vesicles that fuse with the cell membrane, and insulin enters the bloodstream and begins its job of regulating blood and cell glucose levels. There are factors other than glucose levels that can regulate insulin secretion, and they include KATP channels, cAMPS, beta cell mitochondria, and leucine. ATP is necessary for insulin secretion, and many of these factors control ATP levels, in turn helping to regulate the secretion of insulin into the bloodstream. Deficiencies in insulin or resistance to the protein can lead to diseases including diabetes mellitus and polycystic ovary syndrome. Regulation Of Insulin Secretion Bioinformatics Tool Laverne is a handy bioinformatics tool to help facilitate scientific exploration of related genes, diseases and pathways based on co-citations. Explore more on Regulation Of Insulin Secretion below! For more information on how to use Laverne, please read the How to Guide. Top Research Reagents We have 1036 products for the study of the Regulation Of Insulin Secretion Pathway that can be applied to Chromatin Immunoprecipitation, Western Blot, Immunocytochemistry/Immunoflu Continue reading >>

Metabolic Regulation Of Insulin Secretion - Sciencedirect

Metabolic Regulation Of Insulin Secretion - Sciencedirect

Chapter One - Metabolic Regulation of Insulin Secretion Author links open overlay panel KevinKeane PhilipNewsholme Get rights and content Regulation of metabolic fuel homeostasis is a critical function of -cells, which are located in the islets of Langerhans of the animal pancreas. Impairment of this -cell function is a hallmark of pancreatic -cell failure and may lead to development of type 2 diabetes mellitus. -Cells are essentially fuel sensors that monitor and react to elevated nutrient load by releasing insulin. This response involves metabolic activation and generation of metabolic coupling factors (MCFs) that relay the nutrient signal throughout the cell and induce insulin biosynthesis and secretion. Glucose is the most important insulin secretagogue as it is the primary fuel source in food. Glucose metabolism is central to generation of MCFs that lead to insulin release, most notably ATP. In addition, other classes of nutrients are able to augment insulin secretion and these include members of the lipid and amino acid family of nutrients. Therefore, it is important to investigate the interplay between glucose, lipid, and amino acid metabolism, as it is this mixed nutrient sensing that generate the MCFs required for insulin exocytosis. The mechanisms by which these nutrients are metabolized to generate MCFs, and how they impact on -cell insulin release and function, are discussed in detail in this article. Continue reading >>

Reactome | Regulation Of Insulin Secretion

Reactome | Regulation Of Insulin Secretion

Regulation of insulin secretion (Homo sapiens) Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the incretin hormones Glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1), acetylcholine, and fatty acids. Factors which inhibit insulin secretion include adrenaline and noradrenaline. Increased blood glucose levels from dietary carbohydrate play a dominant role in insulin release from the beta cells of the pancreas. Glucose catabolism in the beta cell is the transducer that links increased glucose levels to insulin release. Glucose uptake and glycolysis generate cytosolic pyruvate; pyruvate is transported to mitochondria and converted both to oxaloacetate which increases levels of TCA cycle intermediates, and to acetyl-CoA which is oxidized to CO2 via the TCA cycle. The rates of ATP synthesis and transport to the cytosol increase, plasma membrane ATP-sensitive inward rectifying potassium channels (KATP channels) close, the membrane depolarizes, and voltage-gated calcium channels in the membrane open (Muoio and Newgard 2008; Wiederkehr and Wollheim 2006). Elevated calcium concentrations near the plasma membrane cause insulin secretion in two phases: an initial high rate within minutes of glucose stimulation and a slow, sustained release lasting longer than 30 minutes. In the initial phase, 50-100 insulin granules already docked at the membrane are exocytosed. Exocytosis is rendered calcium-dependent by Synaptotagmin V/IX, a calcium-binding membrane protein located in the membrane of the Continue reading >>

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