How Does Insulin Signal A Cell To Take In Glucose From The Blood?
Just as we receive and act on signals from our environment, our cells also receive and act on signals from their environment, our bodies. This is a necessary biological occurrence that keeps cells alive and functioning. Insulin is a hormone released by our pancreas that signals cells in a specific way in order to stimulate them to take in, use and store glucose. Function of Insulin After ingesting food, your meal is broken down and digested. As a result, glucose is released into your bloodstream. High concentrations of glucose in the blood are a signal for the beta cells of the pancreas to release insulin. This hormone works like a key to unlock the protective cell membranes and allow the passage of glucose into the cell to be used for energy. Mechanism of Insulin Insulin works to decrease the concentration of glucose in the blood and facilitate transport into the cells by binding to special receptors embedded in their membranes. Although there are some tissues such as the brain and the liver that do not require insulin for glucose uptake, most of our cells would not be able to access blood glucose without it. Glucose is the energy source for all cells and is required for their, and ultimately our, survival. The insulin signaling pathway includes an insulin receptor that is made up of two receptor subunits that are located on the outside of the cell membrane and two subunits that penetrate through the membrane. These subunits are chemically bonded together. The extracellular (outside the cell) subunits contain a binding site for insulin. When insulin binds to the extracellular subunits, it activates a chemical reaction that travels through the linked subunits into the cell. This mechanism sends chemical signals to proteins within the cell and causes them to alter their Continue reading >>
- Cell-Centered: Scientists Embrace Cell-Replacement Therapy for Type 1 Diabetes
- NIHR Signal Insulin pumps not much better than multiple injections for intensive control of type 1 diabetes
- International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #59: Mechanisms of insulin signal transduction Part 3 of 8
Insulin Receptor
The cellular receptor for insulin helps control the utilization of glucose by cells Cells throughout the body are fueled largely by glucose that is delivered through the bloodstream. A complex signaling system is used to control the process, ensuring that glucose is delivered when needed and stored when there is a surplus. Two hormones, insulin and glucagon, are at the center of this signaling system. When blood glucose levels drop, alpha cells in the pancreas release glucagon, which then stimulates liver cells to release glucose into the circulation. When blood glucose levels rise, on the other hand, beta cells in the pancreas release insulin, which promotes uptake of glucose for metabolism and storage. Both hormones are small proteins that are recognized by receptors on the surface of cells. Signal Transduction The receptor for insulin is a large protein that binds to insulin and passes its message into the cell. It has several functional parts. Two copies of the protein chains come together on the outside of the cell to form the receptor site that binds to insulin. This is connected through the membrane to two tyrosine kinases, shown here at the bottom. When insulin is not present, they are held in a constrained position, but when insulin binds, these constraints are released. They first phosphorylate and activate each other, and then phosphorylate other proteins in the signaling network inside the cell. Since the whole receptor is so flexible, researchers have determined its structure in several pieces: the insulin-binding portion is shown here from PDB entry 3loh , the transmembrane segment from 2mfr , and the tyrosine kinase from 1irk . When Things Go Wrong Problems with insulin signaling can impair the proper management of glucose levels in the blood, leading to Continue reading >>
- Effects of Insulin Plus Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in Treating Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
- Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)
- Calculating Insulin Dose
Homeostasis Of Glucose Levels: Hormonal Control And Diabetes
Homeostasis According to the Centers for Disease Control and Prevention, there are almost 26 million people in the United States alone that have diabetes, which is 8.3% of the total U.S. population. With so many Americans suffering from diabetes, how do we treat all of them? Do all of these people now need insulin shots, or are there other ways to treat, or prevent, diabetes? In order to answer these questions, we must first understand the fundamentals of blood glucose regulation. As you may remember, homeostasis is the maintenance of a stable internal environment within an organism, and maintaining a stable internal environment in a human means having to carefully regulate many parameters, including glucose levels in the blood. There are two major ways that signals are sent throughout the body. The first is through nerves of the nervous system. Signals are sent as nerve impulses that travel through nerve cells, called neurons. These impulses are sent to other neurons, or specific target cells at a specific location of the body that the neuron extends to. Most of the signals that the human body uses to regulate body temperature are sent through the nervous system. The second way that signals can be sent throughout the body is through the circulatory system. These signals are transmitted by specific molecules called hormones, which are signaling molecules that travel through the circulatory system. In this lesson, we'll take a look at how the human body maintains blood glucose levels through the use of hormone signaling. Homeostasis of Blood Glucose Levels Glucose is the main source of fuel for the cells in our bodies, but it's too big to simply diffuse into the cells by itself. Instead, it needs to be transported into the cells. Insulin is a hormone produced by the panc Continue reading >>
Introduction
INTRODUCTION Glucose in the blood provides a source of fuel for all tissues of the body. Blood glucose levels are highest during the absorptive period after a meal, during which the stomach and small intestine are breaking down food and circulating glucose to the bloodstream. Blood glucose levels are the lowest during the postabsorptive period, when the stomach and small intestines are empty. Despite having food only periodically in the digestive tract, the body works to maintain relatively stable levels of circulatory glucose throughout the day. The body maintains blood glucose homeostasis mainly through the action of two hormones secreted by the pancreas. These hormones are insulin, which is released when glucose levels are high, and glucagon, which is released when glucose levels are low. The accompanying animation depicts the functions of these hormones in blood glucose regulation. CONCLUSION Throughout the day, the release of insulin and glucagon by the pancreas maintains relatively stable levels of glucose in the blood. During the absorptive period blood glucose levels tend to increase, and this increase stimulates the pancreas to release insulin into the bloodstream. Insulin promotes the uptake and utilization of glucose by most cells of the body. Thus, as long as the circulating glucose supply is high, cells preferentially use glucose as fuel and also use glucose to build energy storage molecules glycogen and fats. In the liver, insulin promotes conversion of glucose into glycogen and into fat. In muscle insulin promotes the use of glucose as fuel and its storage as glycogen. In fat cells insulin promotes the uptake of glucose and its conversion into fats. The nervous system does not require insulin to enable its cells to take up and utilize glucose. If glucose Continue reading >>
Ch 105 - Chemistry And Disease
Diabetes The following is from the WebMD Health "In general, people with diabetes either have a total lack of insulin (type 1 diabetes) or they have too little insulin or cannot use insulin effectively (type 2 diabetes). Type 1 diabetes (formerly called juvenile-onset or insulin-dependent diabetes), accounts for 5% to 10% of all people with diabetes. In type 1 diabetes, the body's immune system destroys the cells that release insulin, eventually eliminating insulin production altogether from the body. Without insulin, cells cannot absorb sugar (glucose), which they need to produce energy. Type 2 diabetes (formerly called mature-onset or non�insulin-dependent diabetes) can develop at any age, but most commonly becomes apparent during adulthood. However, the incidence of type 2 diabetes in children is rising. Type 2 diabetes accounts for the vast majority of people with diabetes�more than 90%. In contrast to type 1 diabetes, type 2 diabetes is characterized by insulin resistance. Insulin resistance refers to the inability of the body tissues to respond properly to insulin. Insulin resistance develops because of multiple factors, including genetics, obesity, increasing age, and having high blood sugar over long periods of time. How are these diseases different? Type 1 diabetes Type 2 diabetes Symptoms usually start in childhood or young adulthood. People often seek medical help because they are seriously ill from sudden symptoms of high blood sugar. May not have symptoms before diagnosis. Usually the disease is discovered in adulthood; however, there is an increasing number of children being diagnosed with the disease. Episodes of low blood sugar level (hypoglycemia) common No episodes of low blood sugar level, unless taking insulin or certain oral diabetes medic Continue reading >>
- Treating gum disease may lessen the burden of heart disease, diabetes, other conditions
- St. Luke’s Spotlights Critical Link Between Type 2 Diabetes and Heart Disease in Partnership with Boehringer Ingelheim and Eli Lilly and Company
- Unprocessed Red and Processed Meats and Risk of Coronary Artery Disease and Type 2 Diabetes An Updated Review of the Evidence
Insulin Plays Many Parts In Glucose Regulation
Life Sciences Institute One of the enduring mysteries of Type 2 diabetes lies in the condition that precedes it—the body's growing loss of sensitivity to its own hormone, insulin, which regulates blood sugar levels. Reversing or at least controlling this desensitization before it becomes full-blown diabetes might be an effective therapy, but the many variables at play in the process of desensitization are not well understood. A U-M study published in the April 10 issue of Nature sheds further light on how insulin regulates the machinery that fat cells use to take glucose out of the blood stream immediately after a meal. Rather than just being a simple signal to the fat cell to start or stop glucose uptake, insulin appears to regulate five or six different steps in the machinery the cell uses in glucose-uptake. Each of these steps regulated by insulin may offer an opportunity to understand diabetes a bit better, says study co-author Alan Saltiel, director of the Life Sciences Institute. "We've learned that there are many different ways to regulate insulin sensitivity, potentially giving us multiple chances to intervene," Saltiel says. Glucose uptake in fat and muscle relies on a transport molecule called Glut4, which captures the sugar molecule at the surface of the cell and then drags it in. In the latest research, a team led by U-M postdoctoral fellow Mayumi Inoue has identified a protein complex called the Exocyst that helps Glut4 dock on the cell surface where it can grab a passing glucose. Insulin signals one of the proteins in this complex, called Exo70, to go to the cell membrane and to assemble the docking complex for Glut4. A mutant form of Exo70 that Saltiel's team made still allowed Glut4 to travel to the cell membrane but interfered with the transporter's a Continue reading >>
Facts About Diabetes And Insulin
Diabetes is a very common disease, which, if not treated, can be very dangerous. There are two types of diabetes. They were once called juvenile-onset diabetes and adult diabetes. However, today we know that all ages can get both types so they are simply called type 1 and type 2 diabetes. Type 1, which occurs in approximately 10 percent of all cases, is an autoimmune disease in which the immune system, by mistake, attacks its own insulin-producing cells so that insufficient amounts of insulin are produced - or no insulin at all. Type 1 affects predominantly young people and usually makes its debut before the age of 30, and most frequently between the ages of 10 and 14. Type 2, which makes up the remaining 90 percent of diabetes cases, commonly affects patients during the second half of their lives. The cells of the body no longer react to insulin as they should. This is called insulin resistance. In the early 1920s, Frederick Banting, John Macleod, George Best and Bertram Collip isolated the hormone insulin and purified it so that it could be administered to humans. This was a major breakthrough in the treatment of diabetes type 1. Insulin Insulin is a hormone. Hormones are chemical substances that regulate the cells of the body and are produced by special glands. The hormone insulin is a main regulator of the glucose (sugar) levels in the blood. Insulin is produced in the pancreas. To be more specific, it's produced by the beta cells in the islets of Langerhans in the pancreas. When we eat, glucose levels rise, and insulin is released into the bloodstream. The insulin acts like a key, opening up cells so they can take in the sugar and use it as an energy source. Sugar is one of the top energy sources for the body. The body gets it in many forms, but mainly as carbohydr Continue reading >>
Physiologic Effects Of Insulin
Stand on a streetcorner and ask people if they know what insulin is, and many will reply, "Doesn't it have something to do with blood sugar?" Indeed, that is correct, but such a response is a bit like saying "Mozart? Wasn't he some kind of a musician?" Insulin is a key player in the control of intermediary metabolism, and the big picture is that it organizes the use of fuels for either storage or oxidation. Through these activities, insulin has profound effects on both carbohydrate and lipid metabolism, and significant influences on protein and mineral metabolism. Consequently, derangements in insulin signalling have widespread and devastating effects on many organs and tissues. The Insulin Receptor and Mechanism of Action Like the receptors for other protein hormones, the receptor for insulin is embedded in the plasma membrane. The insulin receptor is composed of two alpha subunits and two beta subunits linked by disulfide bonds. The alpha chains are entirely extracellular and house insulin binding domains, while the linked beta chains penetrate through the plasma membrane. The insulin receptor is a tyrosine kinase. In other words, it functions as an enzyme that transfers phosphate groups from ATP to tyrosine residues on intracellular target proteins. Binding of insulin to the alpha subunits causes the beta subunits to phosphorylate themselves (autophosphorylation), thus activating the catalytic activity of the receptor. The activated receptor then phosphorylates a number of intracellular proteins, which in turn alters their activity, thereby generating a biological response. Several intracellular proteins have been identified as phosphorylation substrates for the insulin receptor, the best-studied of which is insulin receptor substrate 1 or IRS-1. When IRS-1 is activa Continue reading >>
Overview Of Insulin Signaling Pathways
Introduction Insulin is a hormone released by pancreatic beta cells in response to elevated levels of nutrients in the blood. Insulin triggers the uptake of glucose, fatty acids and amino acids into liver, adipose tissue and muscle and promotes the storage of these nutrients in the form of glycogen, lipids and protein respectively. Failure to uptake and store nutrients results in diabetes. Type-1 diabetes is characterized by the inability to synthesize insulin, whereas in type-2 diabetes the body becomes resistant to the effects of insulin, presumably because of defects in the insulin signaling pathway. A. Glucose storage and uptake The insulin receptor is composed of two extracellular α subunits and two transmembrane β subunits linked together by disulphide bonds (Figure 1). Binding of insulin to the α subunit induces a conformational change resulting in the autophosphorylation of a number of tyrosine residues present in the β subunit (Van Obberghen et al., 2001). These residues are recognized by phosphotyrosine-binding (PTB) domains of adaptor proteins such as members of the insulin receptor substrate family (IRS) (Saltiel and Kahn 2001; Lizcano and Alessi 2002). Receptor activation leads to the phosphorylation of key tyrosine residues on IRS proteins, some of which are recognized by the Src homology 2 (SH2) domain of the p85 regulatory subunit of PI3-kinase (a lipid kinase). The catalytic subunit of PI3-kinase, p110, then phosphorylatesphosphatidylinositol (4,5) bisphosphate [PtdIns(4,5)P2] leading to the formation of Ptd(3,4,5)P3. A key downstream effector of Ptd(3,4,5)P3 is AKT, which is recruited to the plasma membrane. Activation of AKT also requires the protein kinase 3-phosphoinositide dependent protein kinase-1 (PDK1), which in combination w Continue reading >>
Insulin Resistance
Please note: reference image is displayed in place of Flash media. Insulin resistance is a condition in which the body cannot use insulin efficiently. About 60 million Americans have insulin resistance. Insulin is a hormone produced by the pancreas that instructs cells (in the muscle, fat and liver) to take up glucose (sugar) from the blood stream when there is too much glucose in the blood. In insulin resistance, cells of the body do not respond to insulin to efficiently remove glucose. The pancreas responds by making more insulin to try to keep blood glucose levels normal. The insulin producing cells of the pancreas slowly become defective and eventually reduce in number. As a result, blood glucose levels rise over time causing diabetes to develop. Insulin resistance is the core metabolic disorder associated with type 2 diabetes. One in four people develop type 2 diabetes, which can increase the risk for heart disease and stroke. Risk factors for insulin resistance: Family History of type 2 diabetes Race or Ethnic Background of African, Latino, Native American descent Being Overweight (more than 20% over optimal body weight) Hypertension or high blood pressure Increasing age raises risk Previous Gestational Diabetes or delivering a baby over 9 lbs There are often no signs or symptoms of insulin resistance. If you have a mild or moderate form of insulin resistance, blood tests may show normal or high blood glucose (hyperglycemia) and high levels of insulin (hyperinsulinemia) at the same time. One test usually does not confirm insulin resistance, but a combination of tests can: Fasting insulin blood test Glucose tolerance testing Physical exam and medical history There are a few things you can do that can help prevent insulin resistance. Physical activity Weight loss He Continue reading >>
Insulin Receptor And Type 2 Diabetes
Part 2 of two animations about type 2 diabetes. This animation describes the role of the insulin receptor in type 2 diabetes. It focuses on the recent discovery of how the hormone insulin actually binds to the receptor on the surface of cells, as determined by Professor Mike Lawrence's laboratory at the Walter and Eliza Hall Institute. Insulin binds to the receptor protein on the cell surface and instructs the cell to take up glucose from the blood for use as an energy source. In type 2 diabetes, we believe that insulin binds to the receptor normally, but the signal is not sent into the cell, the cells do not take up glucose and the resulting high blood glucose levels cause organ damage over time. Understanding how insulin interacts with its receptor is fundamental to the development of novel insulin for the treatment of diabetes. Maja Divjak, 2015 Continue reading >>
- Effects of Insulin Plus Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in Treating Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
- Relative contribution of type 1 and type 2 diabetes loci to the genetic etiology of adult-onset, non-insulin-requiring autoimmune diabetes
- Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)
Video: How Diabetes Affects Your Blood Sugar
Your body uses glucose for energy. Glucose metabolism requires insulin, a hormone produced by your pancreas. Here's how normal glucose metabolism works, and what happens when you have diabetes — a disease where your body either can't produce enough insulin or it can't use insulin properly. The food you eat consists of three basic nutrients: carbohydrates, protein and fat. During digestion, chemicals in your stomach break down carbohydrates into glucose, which is absorbed into your bloodstream. Your pancreas responds to the glucose by releasing insulin. Insulin is responsible for allowing glucose into your body's cells. When the glucose enters your cells, the amount of glucose in your bloodstream falls. If you have type 1 diabetes, your pancreas doesn't secrete insulin — which causes a buildup of glucose in your bloodstream. Without insulin, the glucose can't get into your cells. If you have type 2 diabetes, your pancreas secretes less insulin than your body requires because your body is resistant to its effect. With both types of diabetes, glucose cannot be used for energy, and it builds up in your bloodstream — causing potentially serious health complications. Continue reading >>
Insulin Signaling And The Regulation Of Glucose Transport
Go to: GLUT4 TRANSLOCATION OCCURS IN MULTIPLE STAGES In the absence of insulin, Glut4 slowly recycles between the plasma membrane and vesicular compartments within the cell, where most of the Glut4 resides. Insulin stimulates the translocation of a pool of Glut4 to the plasma membrane, through a process of targeted exocytosis (4,5) (Figure 1). At the same time, Glut4 endocytosis is attenuated (6,7). Thus, the rate of glucose transport into fat and muscle cells is governed by the concentration of Glut4 at the cell surface and the duration for which the protein is maintained at this site. There is substantial evidence that Glut4 exists in specialized vesicles sequestered within the cell, but the precise intracellular location and trafficking pathways of these vesicles are unclear. Following internalization, Glut4 is localized into tubulovesicular and vesicular structures that are biochemically distinct from but possibly interacting with the recycling endosomal network (8). In adipocytes, these vesicles are retained in a perinuclear region in the cell via an unknown mechanism that might involve a tethering protein (9) or continuous futile recycling (10). The Glut4 compartment is enriched in the v-SNARE (soluble N-ethylmaleimide sensitive factor attachment protein) protein VAMP2 (vesicle-associated membrane protein 2) but not the related VAMP3/cellubrevin isoform that is present in recycling endosome (11). Consistent with these data, ablation of transferrin receptor containing endosomes does not impair insulin-stimulated Glut4 translocation (12). The microtubule network and actin cytoskeleton play a role in Glut4 trafficking, either by linking signaling components or by directing movement of vesicles from the perinuclear region to the plasma membrane in response to insulin. Continue reading >>
Insulin Signaling -- Movie Narrative
A biological individual consists of multiple organs with specialized functions. For the organism to function properly in its environment, these organs must communicate. This communication often involves a signal sent from one location to another that instructs the second organ about the status of some cellular feature. Glucose is a good example. Glucose is a critical product of digestion. It is an essential energy source for cellular metabolism. This energy is produced when glucose is used as a substrate for glycolysis and then the Krebs or Citric Acid Cycle. Following the digestion of food, higher levels of glucose circulate through the blood stream where it enters different cell types. In muscle cells glucose is readily used to produce energy and is also stored as glycogen, a secondary short term energy source. In fat cells, glucose is used for Triglyceride production, and acts as an important energy reserve molecule. Here we will illustrate the signaling pathway that occurs when glucose is at high levels. This pathway involves multiple proteins and signaling events. This is termed cytoplasmic signaling. Different types of cells perform similar signaling steps in response to changes in their environment. In the Protein Recycling Animation we see a group of storage vesicles enriched with GLUT4 proteins continuously recycling from the Cell Membrane to an inactive location in the cytosol. GLUT4 is a protein that facilitates the movement of glucose into the cell. When high levels of glucose are detected by beta cells in the pancreas, insulin is released by the cells. The insulin circulates through the blood stream until it binds to an insulin receptor embedded in the cell membrane of a muscle, fat, or brain cell. Once the insulin binds to the receptor, phosphate groups ar Continue reading >>
Glucose Insulin And Diabetes
Every cell in the human body needs energy to survive and do its different functions. If we're talking about a brain cell, it needs energy to keep stimulating other brain cells and sending on signals and messages. If it's a muscle cell, it needs energy to contract. They need energy just to do the basic functions of a cell. And the place that they get that energy from, or the primary source of that energy, is from glucose. Glucose is a simple sugar. If you were to actually taste glucose, it would taste sweet. And glucose gets delivered to cells through the bloodstream. So this right here, I'm drawing some blood that's passing by a cell. Maybe the blood is going in that direction over there. And inside the blood, let me draw some small glucose molecules passing by. And so in an ideal situation, when a cell needs energy, glucose will enter the cell. Unfortunately, it's not that simple for the great majority of cells in the human body. The glucose won't enter by itself. It needs the assistance of a hormone or a molecule called insulin. So let me label all of these. This right here is the glucose, and it needs insulin. So let me draw insulin as these magenta molecules right over here. That over there, that is insulin. And the surface of the cells, they have insulin receptors on them. And I'm just drawing very simplified versions of them, kind of a place where these magenta circles can attach, can bind. And what happens is, in order for the glucose to be taken up by the cell, insulin has to attach to these receptors, which unlocks the channels for glucose. In order for the glucose to go in, insulin has to bind to the insulin receptors. And then, once that happens, then the glucose can be taken up by the cell. Now, unfortunately, things don't always work as planned. So let me d Continue reading >>
- Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis
- Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis
- Postprandial Blood Glucose Is a Stronger Predictor of Cardiovascular Events Than Fasting Blood Glucose in Type 2 Diabetes Mellitus, Particularly in Women: Lessons from the San Luigi Gonzaga Diabetes Study
