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Insulin Is Secreted By The

Pancreatic Β-cells Secrete Insulin In Fast- And Slow-release Forms

Pancreatic Β-cells Secrete Insulin In Fast- And Slow-release Forms

Insulin vesicles contain a chemically rich mixture of cargo that includes ions, small molecules, and proteins. At present, it is unclear if all components of this cargo escape from the vesicle at the same rate or to the same extent during exocytosis. Here, we demonstrate through real-time imaging that individual rat and human pancreatic β-cells secrete insulin in heterogeneous forms that disperse either rapidly or slowly. In healthy pancreatic β-cells maintained in culture, most vesicles discharge insulin in its fast-release form, a form that leaves individual vesicles in a few hundred milliseconds. The fast-release form of insulin leaves vesicles as rapidly as C-peptide leaves vesicles. Healthy β-cells also secrete a slow-release form of insulin that leaves vesicles more slowly than C-peptide, over times ranging from seconds to minutes. Individual β-cells make vesicles with both forms of insulin, though not all vesicles contain both forms of insulin. In addition, we confirm that insulin vesicles store their cargo in two functionally distinct compartments: an acidic solution, or halo, and a condensed core. Thus, our results suggest two important features of the condensed core: 1) It exists in different states among the vesicles undergoing exocytosis and 2) its dissolution determines the availability of insulin during exocytosis. Insufficient insulin secretion in the face of insulin resistance leads to the disease type 2 diabetes (1). The mechanism responsible for insufficient insulin secretion remains unclear. Before it is possible to understand why insulin secretion fails to compensate for insulin resistance during the progression of type 2 diabetes (2), it is essential to understand insulin secretion at all levels of biological complexity, ranging from the whole p 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 >>

Pancreas

Pancreas

The pancreas is a glandular organ in the upper abdomen, but really it serves as two glands in one: a digestive exocrine gland and a hormone-producing endocrine gland. Functioning as an exocrine gland, the pancreas excretes enzymes to break down the proteins, lipids, carbohydrates, and nucleic acids in food. Functioning as an endocrine gland, the pancreas secretes the hormones insulin and glucagon to control blood sugar levels throughout the day. Both of these diverse functions are vital to the body’s survival. Continue Scrolling To Read More Below... Click To View Large Image Related Anatomy: Body of Pancreas Common Bile Duct Head of Pancreas Kidneys Neck of Pancreas Pancreatic Notch Small Intestine Tail of Pancreas Continued From Above... Anatomy of the Pancreas The pancreas is a narrow, 6-inch long gland that lies posterior and inferior to the stomach on the left side of the abdominal cavity. The pancreas extends laterally and superiorly across the abdomen from the curve of the duodenum to the spleen. The head of the pancreas, which connects to the duodenum, is the widest and most medial region of the organ. Extending laterally toward the left, the pancreas narrows slightly to form the body of the pancreas. The tail of the pancreas extends from the body as a narrow, tapered region on the left side of the abdominal cavity near the spleen. Glandular tissue that makes up the pancreas gives it a loose, lumpy structure. The glandular tissue surrounds many small ducts that drain into the central pancreatic duct. The pancreatic duct carries the digestive enzymes produced by endocrine cells to the duodenum. The pancreas is classified as a heterocrine gland because it contains both endocrine and exocrine glandular tissue. The exocrine tissue makes up about 99% of the pancrea Continue reading >>

The Pancreas

The Pancreas

Overview of Pancreatic Islets Pancreatic islets, also called the islets of Langerhans, are regions of the pancreas that contain its hormone-producing endocrine cells. Learning Objectives Differentiate among the types of pancreatic islet cells Key Takeaways Key Points The pancreatic islets are small islands of cells that produce hormones that regulate blood glucose levels. Hormones produced in the pancreatic islets are secreted directly into the bloodstream by five different types of cells. The alpha cells produce glucagon, and make up 15–20% of total islet cells. The beta cells produce insulin and amylin, and make up 65–80% of the total islet cells. The delta cells produce somatostatin, and make up 3–10% of the total islet cells. The gamma cells produce pancreatic polypeptide, and make up 3–5% of the total islet cells. The epsilon cells produce ghrelin, and make up less than 1% of the total islet cells. The feedback system of the pancreatic islets is paracrine, and is based on the activation and inhibition of the islet cells by the endocrine hormones produced in the islets. Key Terms endocrine: Produces internal secretions that are transported around the body by the bloodstream. paracrine: Describes a hormone or other secretion released from endocrine cells into the surrounding tissue rather than into the bloodstream. exocrine: Produces external secretions that are released through a duct. The pancreas serves two functions, endocrine and exocrine. The exocrine function of the pancreas is involved in digestion, and these associated structures are known as the pancreatic acini. The pancreatic acini are clusters of cells that produce digestive enzymes and secretions and make up the bulk of the pancreas. The endocrine function of the pancreas helps maintain blood gl Continue reading >>

Insulin Secretion And Sensitivity

Insulin Secretion And Sensitivity

Introduction In the 1930s Sir Harold Himsworth devised a primitive test of glucose disposal in response to insulin injection, and made the key observation that lean young people with or without diabetes respond similarly, whereas older overweight people with diabetes require much more insulin to achieve the same effect. From this he inferred that there were two types of diabetes: an insulin-sensitive form due to simple insulin deficiency, and an insulin-insensitive form in which the tissues were resistant to the actions of insulin.[1] In recent decades, observations in high-risk relatives have shown that clinical onset of type 1 diabetes is preceded by progressive glucose intolerance, loss of the FPIR, and loss of pulsatile insulin secretion. Progression to diabetes is more rapid in those who are less sensitive to insulin. Insulin secretion There are sub-populations of beta cells within healthy islets, and these have varying levels of responsiveness to glucose. Those with a low threshold for response are more active at normal glucose levels; others cut in at higher glucose levels.[2] Fully functional beta cells are metabolically very active, shedding and replacing 30–50% of their surface membrane daily in the course of insulin secretion. A lean healthy individual might secrete about 35 units of insulin per day, yet will have about 10 times this amount stored within his pancreas. By contrast, an obese insulin-resistant person might need to produce >100 units daily to maintain normal blood glucose levels. Type 1 diabetes results from progressive beta cell loss by apoptosis, thus increasing the work-load of the residue. A further consequence is loss of beta to beta cell communication and an altered cell-to-cell (paracrine) interaction between beta cells and glucagon-prod Continue reading >>

Dispatch Insulin Secretion: Feed-forward Control Of Insulin Biosynthesis?

Dispatch Insulin Secretion: Feed-forward Control Of Insulin Biosynthesis?

Introduction Insulin, the body's chief anabolic hormone, is synthesised in pancreatic islets, and released when the blood glucose level rises. Defective insulin release contributes to non-insulin-dependent diabetes mellitus (NIDDM). A new study has now shown that targeted inactivation of insulin receptors in pancreatic β cells, by genetic manipulation of mice using the Cre–loxP system, produces animals which suffer insulin secretory defects akin to those found in human patients with NIDDM [1]. Furthermore, in vitro studies have shown that exogenous insulin added directly to normal islets causes transcriptional up-regulation of the preproinsulin gene [2], activation of protein translational machinery [3] and insulin secretion [4]. The important implication is that insulin acts back on the β cells to promote its own production. Insulin biosynthesis In mammals, an increase in the blood glucose level enhances transcription of the preproinsulin gene [5] and translation of preproinsulin mRNA [6], and stimulates the release of insulin by regulated exocytosis of the mature hormone. The latter process, which resembles the regulated release of neurotransmitters from neurons, involves Ca2+ influx through L-type channels, an increase in intracellular Ca2+ concentration and exocytosis from dense-core secretory vesicles (Figure 1) [7]. Figure 1. The possible interplay between the action of glucose (top left) and secreted insulin (red squares) one preproinsulin gene expression in this islet β cell. (See text for details.) Is secreted insulin involved in stimulating insulin gene expression? Certainly, the order of events in response to glucose is compatible with this idea. Insulin secretion is activated seconds to minutes after an elevation in the glucose level, preproinsulin mRNA 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 >>

What Is Insulin?

What Is Insulin?

Insulin is a hormone; a chemical messenger produced in one part of the body to have an action on another. It is a protein responsible for regulating blood glucose levels as part of metabolism.1 The body manufactures insulin in the pancreas, and the hormone is secreted by its beta cells, primarily in response to glucose.1 The beta cells of the pancreas are perfectly designed "fuel sensors" stimulated by glucose.2 As glucose levels rise in the plasma of the blood, uptake and metabolism by the pancreas beta cells are enhanced, leading to insulin secretion.1 Insulin has two modes of action on the body - an excitatory one and an inhibitory one:3 Insulin stimulates glucose uptake and lipid synthesis It inhibits the breakdown of lipids, proteins and glycogen, and inhibits the glucose pathway (gluconeogenesis) and production of ketone bodies (ketogenesis). What is the pancreas? The pancreas is the organ responsible for controlling sugar levels. It is part of the digestive system and located in the abdomen, behind the stomach and next to the duodenum - the first part of the small intestine.4 The pancreas has two main functional components:4,5 Exocrine cells - cells that release digestive enzymes into the gut via the pancreatic duct The endocrine pancreas - islands of cells known as the islets of Langerhans within the "sea" of exocrine tissue; islets release hormones such as insulin and glucagon into the blood to control blood sugar levels. Islets are highly vascularized (supplied by blood vessels) and specialized to monitor nutrients in the blood.2 The alpha cells of the islets secrete glucagon while the beta cells - the most abundant of the islet cells - release insulin.5 The release of insulin in response to elevated glucose has two phases - a first around 5-10 minutes after g 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 >>

You And Your Hormones

You And Your Hormones

What is insulin? Insulin is a hormone made by an organ located behind the stomach called the pancreas. Here, insulin is released into the bloodstream by specialised cells called beta cells found in areas of the pancreas called islets of langerhans (the term insulin comes from the Latin insula meaning island). Insulin can also be given as a medicine for patients with diabetes because they do not make enough of their own. It is usually given in the form of an injection. Insulin is released from the pancreas into the bloodstream. It is a hormone essential for us to live and has many effects on the whole body, mainly in controlling how the body uses carbohydrate and fat found in food. Insulin allows cells in the muscles, liver and fat (adipose tissue) to take up sugar (glucose) that has been absorbed into the bloodstream from food. This provides energy to the cells. This glucose can also be converted into fat to provide energy when glucose levels are too low. In addition, insulin has several other metabolic effects (such as stopping the breakdown of protein and fat). How is insulin controlled? When we eat food, glucose is absorbed from our gut into the bloodstream. This rise in blood glucose causes insulin to be released from the pancreas. Proteins in food and other hormones produced by the gut in response to food also stimulate insulin release. However, once the blood glucose levels return to normal, insulin release slows down. In addition, hormones released in times of acute stress, such as adrenaline, stop the release of insulin, leading to higher blood glucose levels. The release of insulin is tightly regulated in healthy people in order to balance food intake and the metabolic needs of the body. Insulin works in tandem with glucagon, another hormone produced by the pan 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 >>

Endocrine Pancreas

Endocrine Pancreas

This page outlines information on the pancreas. Several hormones participate in the regulation of carbohydrate metabolism. Four of them are secreted by the cells of the islets of Langerhans in the pancreas: two, insulin and glucagon, with major actions on glucose metabolism and two, somatostatin and pancreatic polypeptide, with modulating actions on insulin and glucagon secretion. Other hormones affecting carbohydrate metabolism include: epinephrine, thyroid hormones, glucocorticoids, and growth hormone. Structure and Function of the Pancreas The pancreas lies inferior to the stomach, in a bend of the duodenum. It is both an endocrine and an exocrine gland. The exocrine functions are concerned with digestion. The endocrine function consists primarily of the secretion of the two major hormones, insulin and glucagon. Four cell types have been identified in the islets, each producing a different hormone with specific actions: * A cells produce glucagon; * B cells produce insulin; * D cells produce somatostatin; and * F or D1 cells produce pancreatic polypeptide. These hormones are all polypeptides. Insulin is secreted only by the B cells whereas the other hormones are also secreted by the gastrointestinal mucosa and somatostatin is also found in the brain. Both insulin and glucagon are important in the regulation of carbohydrate, protein and lipid metabolism: Insulin is an anabolic hormone, that is, it increases the storage of glucose, fatty acids and amino acids in cells and tissues. Glucagon is a catabolic hormone, that is, it mobilizes glucose, fatty acids and amino acids from stores into the blood. Somatostatin may regulate, locally, the secretion of the other pancreatic hormones; in brain (hypothalamus) and spinal cord it may act as a neurohormone and neurotransmitter 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

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 >>

How Insulin And Glucagon Work

How Insulin And Glucagon Work

Insulin and glucagon are hormones that help regulate the levels of blood glucose, or sugar, in your body. Glucose, which comes from the food you eat, moves through your bloodstream to help fuel your body. Insulin and glucagon work together to balance your blood sugar levels, keeping them in the narrow range that your body requires. These hormones are like the yin and yang of blood glucose maintenance. Read on to learn more about how they function and what can happen when they don’t work well. Insulin and glucagon work in what’s called a negative feedback loop. During this process, one event triggers another, which triggers another, and so on, to keep your blood sugar levels balanced. How insulin works During digestion, foods that contain carbohydrates are converted into glucose. Most of this glucose is sent into your bloodstream, causing a rise in blood glucose levels. This increase in blood glucose signals your pancreas to produce insulin. The insulin tells cells throughout your body to take in glucose from your bloodstream. As the glucose moves into your cells, your blood glucose levels go down. Some cells use the glucose as energy. Other cells, such as in your liver and muscles, store any excess glucose as a substance called glycogen. Your body uses glycogen for fuel between meals. Read more: Simple vs. complex carbs » How glucagon works Glucagon works to counterbalance the actions of insulin. About four to six hours after you eat, the glucose levels in your blood decrease, triggering your pancreas to produce glucagon. This hormone signals your liver and muscle cells to change the stored glycogen back into glucose. These cells then release the glucose into your bloodstream so your other cells can use it for energy. This whole feedback loop with insulin and gluca Continue reading >>

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