diabetestalk.net

Secretion Of Insulin

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

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 >>

Secretion Of Insulin In Response To Diet And Hormones

Secretion Of Insulin In Response To Diet And Hormones

1. The Dual Nature of the Pancreas The pancreas is a complex gland active in digestion and metabolism through secretion of digestive enzymes from the exocrine portion and hormones from the endocrine portion. The exocrine pancreas, which accounts for more than 95% of the pancreas mass, is structurally comprised of lobules, with acinar cells surrounding a duct system. The endocrine pancreas makes up only 2% of the pancreatic mass and is organized into the islets of Langerhans— small semi-spherical clusters of about 1500 cells (55) dispersed throughout the pancreatic parenchyme— which produce and secrete hormones critical for glucose homeostasis. The existence of islets was first described by Paul Langerhans in the 1890s, and the functional role of islets in glucose homeostasis was first demonstrated in 1890 when Joseph von Mering and colleagues showed that dogs developed diabetes mellitus following pancreatectomy (17). Though islet mass may vary between individuals—an example is the increase in the setting of adult obesity (64)— the average adult human pancreas is estimated to contain one to two million islets (24, 73). In the human pancreas, the concentration of islets is up to two times higher in the tail compared to the head and neck. However, the cellular composition and architectural organization of cell types within the islets is preserved throughout the pancreas (82). Each pancreatic islet is composed of α, β, δ, ε and PP cells; these are primarily endocrine (hormone-secreting) cells, containing numerous secretory granules with stored hormone molecules, ready for release upon receipt of the appropriate stimulus. Insulin-producing b cells are the most common cell type, making up 50-70% of islet mass, with small islets containing a greater percentage of b Continue reading >>

Handbook Of Diabetes, 4th Edition, Excerpt #4: Normal Physiology Of Insulin Secretion And Action

Handbook Of Diabetes, 4th Edition, Excerpt #4: Normal Physiology Of Insulin Secretion And Action

Insulin is synthesized in and secreted from the β-cells within the islets of Langerhans in the pancreas. The normal pancreas has about 1 million islets, which constitute about 2-3% of the gland’s mass. All of the islet cell types are derived embryologically from endodermal outgrowths of the fetal gut. The islets can be identified easily with various histological stains, such as hematoxylin and eosin (Figure 5.1), with which the cells react less intensely than does the surrounding exocrine tissue. The islets vary in size from a few dozen to several thousands of cells and are scattered irregularly throughout the exocrine pancreas…. The main cell types of the pancreatic islets are β-cells that produce insulin, α-cells that secrete glucagon, δ cells that produce somatostatin and PP cells that produce pancreatic polypeptide. The different cell types can be identified by immunostaining techniques, in situ hybridization for their hormone products (using nucleotide probes complementary to the target mRNA) and the electron microscope appearance of their secretory granules. The β-cells are the most numerous cell type and are located mainly in the core of the islet, while α and δ cells are located in the periphery (Figure 5.2). Islet cells interact with each other through direct contact and through their products (e.g. glucagon stimulates insulin secretion and somatostatin inhibits insulin and glucagon secretion) (Figure 5.3). The blood flow within the islets is organized centrifugally so that the different cell types are supplied in the sequence β → α → δ . Insulin also has an ‘autocrine’ (self-regulating) effect that alters the transcription of insulin and glucokinase genes in the β cell. The pancreatic islets are densely innervated with autonomic and pept 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 >>

Pancreas And Insulin

Pancreas And Insulin

Your pancreas is one of the organs of your digestive system. It lies in your abdomen, behind your stomach. It is a long thin structure with 2 main functions: producing digestive enzymes to break down food; and producing the hormones insulin and glucagon to control sugar levels in your body. Production of digestive enzymes The pancreas produces secretions necessary for you to digest food. The enzymes in these secretions allow your body to digest protein, fat and starch from your food. The enzymes are produced in the acinar cells which make up most of the pancreas. From the acinar cells the enzymes flow down various channels into the pancreatic duct and then out into the duodenum. The secretions are alkaline to balance the acidic juices and partially digested food coming into the duodenum from the stomach. Production of hormones to control blood sugar levels A small proportion (1-2 per cent) of the pancreas is made up of other types of cells called islets of Langerhans. These cells sit in tiny groups, like small islands, scattered throughout the tissue of the pancreas. The islets of Langerhans contain alpha cells which secrete glucagon and beta cells which secrete insulin. Insulin and glucagon are hormones that work to regulate the level of sugar (glucose) in the body to keep it within a healthy range. Unlike the acinar cells, the islets of Langerhans do not have ducts and secrete insulin and glucagon directly into the bloodstream. Depending on what you’ve eaten, how much exercise your muscles are doing, and how active your body cells are, the amount of glucose in your bloodstream and cells varies. These 2 hormones have the job of keeping tight control of the amount of glucose in your blood so that it doesn’t rise or fall outside of healthy limits. How insulin works I Continue reading >>

Insulin Synthesis And Secretion

Insulin Synthesis And Secretion

Insulin is a small protein, with a molecular weight of about 6000 Daltons. It is composed of two chains held together by disulfide bonds. The figure to the right shows a molecular model of bovine insulin, with the A chain colored blue and the larger B chain green. You can get a better appreciation for the structure of insulin by manipulating such a model yourself. The amino acid sequence is highly conserved among vertebrates, and insulin from one mammal almost certainly is biologically active in another. Even today, many diabetic patients are treated with insulin extracted from pig pancreas. Biosynthesis of Insulin Insulin is synthesized in significant quantities only in beta cells in the pancreas. The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin. Proinsulin consists of three domains: an amino-terminal B chain, a carboxy-terminal A chain and a connecting peptide in the middle known as the C peptide. Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin. Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm. When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood. C peptide is also secreted into blood, but has no known biological activity. Control of Insulin Secretion Insulin is secreted in primarily in response to elevated blood concentrations of glucose. This makes sense because insulin is "in charge" of facilitating glucose entry into cells. Some neural stimuli (e.g. sight and taste of food) 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 >>

Insulin Synthesis, Secretion And Degradation

Insulin Synthesis, Secretion And Degradation

Insulin is produced by the beta-cells in the pancreatic islets. Its synthesis involves sequential cleavage of its two precursor molecules preproinsulin and proinsulin. The gene encoding preproinsulin is located on the short arm of chromosome 11. Following synthesis the preproinsulin molecule undergoes rapid enzymatic cleavage to proinsulin, which contains the insulin A and B chains linked by connecting or C-peptide. Proinsulin is packaged into small granules within the Golgi complex, which then migrate towards the cell surface. As the granules mature, proteases split proinsulin into equal amounts of insulin and C-peptide, allowing the insulin molecule, consisting of A and B chains linked by two disulfide bridges, to assume its active configuration. Insulin forms microcrystals around zinc ions within the secretory granules, producing hexamers which separate rapidly following release. Rising intracellular glucose triggers insulin secretion by activation of glucokinase followed by an increase in intracellular ATP, resulting in closure of the ATP-sensitive potassium channel. This causes depolarisation of the beta-cell membrane and the influx of calcium ions, leading to fusion of the insulin granules with the cell membrane and the release of insulin, C-peptide and other molecules into the circulation by exocytosis. The insulin molecule The primary structure of the insulin molecule was elucidated by Frederick Sanger in 1951, and its tertiary structure by Dorothy Hodgkin in 1969. Human insulin is a protein consisting of a A-chain with 21 amino acids, and a B-chain with 30 amino acids. The chains are linked by two disulfide bridges between the cystein residues at positions A7 and B7, and A20 and C19. An additional disulfide-bridge connects the cystein residues at A6 and A11, wh Continue reading >>

Secretion Of Insulin And Glucagon

Secretion Of Insulin And Glucagon

Coordination of metabolism in and between our various tissues is the cornerstone of life. The activities of many of the steps in metabolism are controlled by circulating hormones, the most prominent of these being the pancreatic hormones insulin and glucagon. Control of the rates of secretion of these two peptides is necessary to assure a stable inner milieu, allowing us to adjust our metabolism to meet the stresses of life. Meals, running after the bus, rest and sleep; all require adjustments in metabolic rates to allow us to function. Many of my readers perhaps associate insulin with sugar metabolism and diabetes. It is important to realize insulin, glucagon and many other hormones also control protein and lipid metabolism, feelings of hunger and satiation as well as sugar metabolism. The pancreas contains clusters of cells known as the Islets of Langerhans. It is here that insulin and glucagon are produced and released. The islets contain three cell types: alpha cells that produce glucagon, beta cells that produce insulin, and delta cells where somatostatin is synthesized. Together, these cells and their hormone products are responsible for the minute-to-minute regulation of metabolism. Seemingly minor aberrations in function of these cells have large and often devastating effects on an individual's health. Production and secretion of these hormones is a full-time job. We often think of insulin release as a result of food intake while, in fact, about 50 % of the insulin secreted daily comes in periods between meals. Let us now look at how the body controls secretion of insulin. The initiation of insulin secretion from the beta cell follows uptake of Ca+2 ions over the cell's outer membrane. The Ca+2 channel responsible for this is regulated by degree of polarization Continue reading >>

Nutrient Regulation Of Insulin Secretion And Action

Nutrient Regulation Of Insulin Secretion And Action

Introduction Homoeostatic regulation of fuel metabolism in the body is a tightly controlled process and dysregulation can lead to pathological conditions such as diabetes mellitus (DM), cardiovascular disease, stroke, renal disease and other manifestations of the metabolic syndrome. Glucose, the body's primary metabolic fuel source, is ingested usually in polymeric form following the consumption of a mixed meal, and the subsequent postprandial elevation in blood glucose level is stringently modulated by the release of the pancreatic hormones insulin and glucagon. These hormones target metabolically active tissues such as muscle, adipose tissue and liver in order to maintain blood glucose concentration within narrow limits (∼4.0–6.0 mmol/l). However, dysregulation of metabolic processes may result in chronic hyperglycaemic, dyslipidaemic or glucolipotoxic conditions that may negatively impact a wide variety of tissues and organs including pancreatic islets, skeletal muscle, adipose tissue and the liver and are frequently observed in DM. According to the International Diabetes Federation (IDF), in 2011, 336 million of the world's population (∼6.4%) had either type 1 (T1DM) or type 2 DM (T2DM), yet the prevalence is continuing to rise at rapid rates and is projected to exceed 550 million by 2030 (Whiting et al. 2011). Furthermore, T2DM is by far the most common form of the disease, representing about 90–95% of DM cases. Pancreatic islets are specialised and highly vascularised structures that monitor the nutrient contents of the blood stream and consist of mainly five cell types; α-cells, β-cells, δ-cells, ghrelin cells (γ-cells) and pancreatic peptide (PP)-secreting cells (Wierup et al. 2014). Islets continually sample blood from the branches of the splenic an Continue reading >>

Kegg Pathway: Insulin Secretion - Homo Sapiens (human)

Kegg Pathway: Insulin Secretion - Homo Sapiens (human)

Insulin secretion - Homo sapiens (human) [ Pathway menu | Organism menu | Pathway entry | Download KGML | Hide description | User data mapping ] Pancreatic beta cells are specialised endocrine cells that continuously sense the levels of blood sugar and other fuels and, in response, secrete insulin to maintain normal fuel homeostasis. Glucose-induced insulin secretion and its potentiation constitute the principal mechanism of insulin release. Glucose is transported by the glucose transporter (GLUT) into the pancreatic beta-cell. Metabolism of glucose generates ATP, which inhibits ATP-sensitive K+ channels and causes voltage-dependent Ca2+ influx. Elevation of [Ca2+]i triggers exocytotic release of insulin granules. Insulin secretion is further regulated by several hormones and neurotransmitters. Peptide hormones, such as glucagon-like peptide 1 (GLP-1), increase cAMP levels and thereby potentiate insulin secretion via the combined action of PKA and Epac2. Achetylcholine (ACh), a major parasympathetic neurotransmitter, binds to Gq-coupled receptors and activates phospholipase C- (PLC-), and the stimulatory effects involve activation of protein kinase C (PKC), which stimulates exocytosis. In addition, ACh mobilizes intracellular Ca2+ by activation of IP3 receptors. Continue reading >>

Secretion Of Insulin And Glucagon

Secretion Of Insulin And Glucagon

As I have already mentioned, the pancreas contains clusters of cells known as the Islets of Langerhans. They contain three cell types: alpha cells that produce glucagon, beta cells that produce insulin, and delta cells where somatostatin is synthesized. Together, these cells and their hormone products are responsible for the minute-to-minute regulation of metabolism. Metabolism in this case includes storage and release of carbohydrates and lipids, rates of energy production, protein synthesis and even the regulation of hunger. Seemingly minor aberrations in function of these cells have large and often devastating effects on an individual's health. Insulin secretion is stimulated by glucose, some amino acids and fatty acids. Let us take these up individually. Monitoring Blood Glucose. The basic functions and physiology of the beta cell are relatively well understood. A model of the beta cell showing the basic components for insulin secretion is presented below. A glucose "sensor" mechanism, a metabolic coupling to potassium channels to control plasma membrane potential and a voltage dependent Ca++ channel are required to link blood glucose levels to insulin secretion. Insulin containing granules are found in a reserve pool and a "readily released" pool. Let us look at the "glucose sensor" system first. The beta cell's primary function is to correlate release of insulin with changes in blood glucose concentration. Obviously, these cells must have a sensitive glucose-measuring device. Nature has achieved this by equipping the beta cell with a glucose transport protein (GLUT2) and a kinase (glucokinase) both of which have low affinities for glucose. GLUT2 is quite active, but the Km for glucose is around 5 mmol/l. Therefore, transport of glucose into the beta cell is rapid, 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 >>

Insulin

Insulin

Insulin, hormone that regulates the level of sugar (glucose) in the blood and that is produced by the beta cells of the islets of Langerhans in the pancreas. Insulin is secreted when the level of blood glucose rises—as after a meal. When the level of blood glucose falls, secretion of insulin stops, and the liver releases glucose into the blood. Insulin was first reported in pancreatic extracts in 1921, having been identified by Canadian scientists Frederick G. Banting and Charles H. Best and by Romanian physiologist Nicolas C. Paulescu, who was working independently and called the substance “pancrein.” After Banting and Best isolated insulin, they began work to obtain a purified extract, which they accomplished with the help of Scottish physiologist J.J.R. Macleod and Canadian chemist James B. Collip. Banting and Macleod shared the 1923 Nobel Prize for Physiology or Medicine for their work. Insulin is a protein composed of two chains, an A chain (with 21 amino acids) and a B chain (with 30 amino acids), which are linked together by sulfur atoms. Insulin is derived from a 74-amino-acid prohormone molecule called proinsulin. Proinsulin is relatively inactive, and under normal conditions only a small amount of it is secreted. In the endoplasmic reticulum of beta cells the proinsulin molecule is cleaved in two places, yielding the A and B chains of insulin and an intervening, biologically inactive C peptide. The A and B chains become linked together by two sulfur-sulfur (disulfide) bonds. Proinsulin, insulin, and C peptide are stored in granules in the beta cells, from which they are released into the capillaries of the islets in response to appropriate stimuli. These capillaries empty into the portal vein, which carries blood from the stomach, intestines, and pancrea Continue reading >>

More in diabetes