Diabetes: What’s Insulin Resistance Got To Do With It?
Invisible changes in the body begin long before a person is diagnosed with type 2 diabetes. That’s both bad news (no symptoms mean you won’t know you have it) and good news (you can prevent or delay it if you’re at risk). One of the most important unseen changes? Insulin resistance. Insulin in a Nutshell Insulin is a key player in developing type 2 diabetes. This vital hormone—you can’t survive without it—regulates blood sugar (glucose) in the body, a very complicated process. Here are the high points: The food you eat is broken down into glucose. Glucose enters your bloodstream, which signals the pancreas to release insulin. Insulin helps glucose enter the body’s cells so it can be used for energy. Insulin also signals the liver to store glucose for later use. Glucose enters cells, and glucose levels in the bloodstream decrease, signaling insulin to decrease too. Lower insulin levels alert the liver to release stored glucose so energy is always available, even if you haven’t eaten for a while. That’s when everything works smoothly. But this finely tuned system can quickly get out of whack, as follows: A lot of glucose enters the bloodstream. The pancreas pumps out more insulin to get glucose into cells. Over time, cells stop responding to all that insulin—they’ve become insulin resistant. The pancreas keeps making more insulin to try to make cells respond. Eventually, the pancreas can’t keep up, and glucose keeps rising. Now What? Lots of glucose in the bloodstream is very damaging to the body and needs to be moved into cells as soon as possible. There’s lots of insulin, too, telling the liver and muscles to store glucose. When they’re full, the liver sends the excess glucose to fat cells to be stored as body fat. Yep, weight gain. And what Continue reading >>
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 >>
What Is Insulin?
Insulin is a hormone made by the pancreas that allows your body to use sugar (glucose) from carbohydrates in the food that you eat for energy or to store glucose for future use. Insulin helps keeps your blood sugar level from getting too high (hyperglycemia) or too low (hypoglycemia). The cells in your body need sugar for energy. However, sugar cannot go into most of your cells directly. After you eat food and your blood sugar level rises, cells in your pancreas (known as beta cells) are signaled to release insulin into your bloodstream. Insulin then attaches to and signals cells to absorb sugar from the bloodstream. Insulin is often described as a “key,” which unlocks the cell to allow sugar to enter the cell and be used for energy. If you have more sugar in your body than it needs, insulin helps store the sugar in your liver and releases it when your blood sugar level is low or if you need more sugar, such as in between meals or during physical activity. Therefore, insulin helps balance out blood sugar levels and keeps them in a normal range. As blood sugar levels rise, the pancreas secretes more insulin. If your body does not produce enough insulin or your cells are resistant to the effects of insulin, you may develop hyperglycemia (high blood sugar), which can cause long-term complications if the blood sugar levels stay elevated for long periods of time. Insulin Treatment for Diabetes People with type 1 diabetes cannot make insulin because the beta cells in their pancreas are damaged or destroyed. Therefore, these people will need insulin injections to allow their body to process glucose and avoid complications from hyperglycemia. People with type 2 diabetes do not respond well or are resistant to insulin. They may need insulin shots to help them better process Continue reading >>
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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- Insulin, glucagon and somatostatin stores in the pancreas of subjects with type-2 diabetes and their lean and obese non-diabetic controls
- Effects of Insulin Plus Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in Treating Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Insulin Signal Transduction Pathway
The insulin transduction pathway is a biochemical pathway by which insulin increases the uptake of glucose into fat and muscle cells and reduces the synthesis of glucose in the liver and hence is involved in maintaining glucose homeostasis. This pathway is also influenced by fed versus fasting states, stress levels, and a variety of other hormones. When carbohydrates are consumed, digested, and absorbed the pancreas senses the subsequent rise in blood glucose concentration and releases insulin to promote an uptake of glucose from the blood stream. When insulin binds to the insulin receptor, it leads to a cascade of cellular processes that promote the usage or, in some cases, the storage of glucose in the cell. The effects of insulin vary depending on the tissue involved, e.g., insulin is most important in the uptake of glucose by muscle and adipose tissue. This insulin signal transduction pathway is composed of trigger mechanisms (e.g., autophosphorylation mechanisms) that serve as signals throughout the cell. There is also a counter mechanism in the body to stop the secretion of insulin beyond a certain limit. Namely, those counter-regulatory mechanisms are glucagon and epinephrine. The process of the regulation of blood glucose (also known as glucose homeostasis) also exhibits oscillatory behavior. On a pathological basis, this topic is crucial to understanding certain disorders in the body such as diabetes, hyperglycemia and hypoglycemia. Transduction pathway[edit] The functioning of a signal transduction pathway is based on extra-cellular signaling that in turn creates a response which causes other subsequent responses, hence creating a chain reaction, or cascade. During the course of signaling, the cell uses each response for accomplishing some kind of a purpose al Continue reading >>
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
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
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Review The Glut4 Glucose Transporter
Figure 1. Structural Features of the Insulin-Regulated GLUT4 Glucose Transporter Protein The unique sensitivity of GLUT4 to insulin-mediated translocation appears to derive from sequences shown in the N-terminal (required phenylalanine) and COOH-terminal (required dileucine and acidic residues) regions. These sequences are likely involved in rapid internalization and sorting of GLUT4 in intracellular membranes termed GLUT4 storage vesicles (GSV), as outlined in Figure 3. See text for further details. GLUT4 Is a Key Determinant of Glucose Homeostasis A central role for GLUT4 in whole-body metabolism is strongly supported by a variety of genetically engineered mouse models where expression of the transporter is either enhanced or ablated in muscle or adipose tissue or both. The whole-body GLUT4−/− mouse itself may be less informative due to upregulation of compensatory mechanisms that may promote survival of these animals (Katz et al., 1995; Stenbit et al., 1996). However, heterozygous GLUT4+/− mice that display decreased GLUT4 protein in muscle and adipose tissue show the expected insulin resistance and propensity toward diabetes that is consistent with a major role of GLUT4 in glucose disposal (Rossetti et al., 1997; Stenbit et al., 1997; Li et al., 2000). Interestingly, overexpression of GLUT4 expression in skeletal muscle of such GLUT4+/− animals through crosses with transgenic mice normalizes insulin sensitivity and glucose tolerance (Tsao et al., 1999). Transgenic mice expressing high levels of GLUT4 in adipose tissue (Shepherd et al., 1993; Tozzo et al., 1995) or in skeletal muscle (Tsao et al., 1996, 2001) in turn are both highly insulin sensitive and glucose tolerant. Conversely, conditional depletion of GLUT4 in either adipose tissue or skeletal muscle c Continue reading >>
- Sodium-Glucose Co-Transporter-2 Inhibitors: An Update on the Evidence for Treatment of Type 2 Diabetes
- Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver
- Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis
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 >>
Insulin's Role In The Human Body
Insulin is a hormone produced by the pancreas that has a number of important functions in the human body, particularly in the control of blood glucose levels and preventing hyperglycemia. It also has an effect on several other areas of the body, including the synthesis of lipids and regulation of enzymatic activity. Insulin and Metabolic Processes The most important role of insulin in the human body is its interaction with glucose to allow the cells of the body to use glucose as energy. The pancreas usually produces more insulin in response to a spike in blood sugar level, for example after eating a meal high in energy. This is because the insulin acts as a “key” to open up the cells in the body and allows the glucose to be used as an energy source. Additionally, when there is excess glucose in the bloodstream, known as hyperglycemia, insulin encourages the storage of glucose as glycogen in the liver, muscle and fat cells. These stores can then be used at a later date when energy requirements are higher. As a result of this, there is less insulin in the bloodstream, and normal blood glucose levels are restored. Insulin stimulates the synthesis of glycogen in the liver, but when the liver is saturated with glycogen, an alternative pathway takes over. This involves the uptake of additional glucose into adipose tissue, leading to the synthesis of lipoproteins. Results Without Insulin In the absence of insulin, the body is not able to utilize the glucose as energy in the cells. As a result, the glucose remains in the bloodstream and can lead to high blood sugar, known as hyperglycemia. Chronic hyperglycemia is characteristic of diabetes mellitus and, if untreated, is associated with severe complications, such as damage to the nervous system, eyes, kidneys and extremitie Continue reading >>
How Insulin Works
Insulin is a hormone made by one of the body's organs called the pancreas. Insulin helps your body turn blood sugar (glucose) into energy. It also helps your body store it in your muscles, fat cells, and liver to use later, when your body needs it. After you eat, your blood sugar (glucose) rises. This rise in glucose triggers your pancreas to release insulin into the bloodstream. Insulin travels through the blood to your body's cells. It tells the cells to open up and let the glucose in. Once inside, the cells convert glucose into energy or store it to use later. Without insulin, your body can't use or store glucose for energy. Instead, the glucose stays in your blood. Continue reading >>
How Does Insulin Transfer Glucose Into Our Cells?
Everyone knows insulin is critical for diabetics, but how many people know how insulin transfers glucose into our cells. At first blush, this process may seem unimportant. After all, who cares? Nonetheless, I would argue that this process is extremely relevant to understanding a lot about diabetes, particularly type 2 diabetes. It is also important to understand because this process can take on more significance the longer you have diabetes, as the transfer of glucose into your cells can begin to break down further. Don’t worry, the process is not that difficult. First, we’ll take a look at how the process is supposed to work. Then, we’ll switch gears and learn what happens when you have type 2 diabetes. Normal Transfer of Glucose Normally, in non-diabetics, insulin is released in small amounts by the pancreas to help our body’s cells process glucose into energy. This is happening all the time, but around meal times, more insulin is produced to help process the increased glucose on our blood. Regulating this process is the beta cells in the pancreas. The beta cells monitor the levels of glucose in the blood and produce the necessary amount of insulin. Insulin is a protein and is carried in the blood plasma, the liquid form of our blood. To get technical, the insulin attaches to beta globulins within the blood plasma. Globulins, both alpha and beta, are responsible for circulating hormones and vitamins throughout your body. As the insulin circulates throughout the body in your blood, it comes into contact with your cells. Your cells are looking for the glucose for energy. When the insulin comes in contact with cell membranes, the insulin causes a cell’s membrane to become more susceptible to glucose entering it. Essentially, the membrane becomes more permeable Continue reading >>
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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 >>
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Nih Study Shows How Insulin Stimulates Fat Cells To Take In Glucose
Findings could aid in understanding diabetes, related conditions. Using high-resolution microscopy, researchers at the National Institutes of Health have shown how insulin prompts fat cells to take in glucose in a rat model. The findings were reported in the Sept. 8 issue of the journal Cell Metabolism. By studying the surface of healthy, live fat cells in rats, researchers were able to understand the process by which cells take in glucose. Next, they plan to observe the fat cells of people with varying degrees of insulin sensitivity, including insulin resistance — considered a precursor to type 2 diabetes (These observations may help identify the interval when someone becomes at risk for developing diabetes. "What we're doing here is actually trying to understand how glucose transporter proteins called GLUT4 work in normal, insulin-sensitive cells," said Karin G. Stenkula, Ph.D., a researcher at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and a lead author of the paper. "With an understanding of how these transporters in fat cells respond to insulin, we could detect the differences between an insulin-sensitive cell and an insulin-resistant cell, to learn how the response becomes impaired. We hope to identify when a person becomes pre-diabetic, before they go on to develop diabetes." Glucose, a simple sugar, provides energy for cell functions. After food is digested, glucose is released into the bloodstream. In response, the pancreas secretes insulin, which directs the muscle and fat cells to take in glucose. Cells obtain energy from glucose or convert it to fat for long-term storage. Like a key fits into a lock, insulin binds to receptors on the cell's surface, causing GLUT4 molecules to come to the cell's surface. As their name impli Continue reading >>
Type 2 Diabetes: What Is It?
When it comes to your body, you probably spend more time thinking about your hair than your hormones. For some people, though, a problem with a hormone called insulin causes a health condition called type 2 diabetes (pronounced: dye-uh-BEE-tees). Diabetes is a disease that affects how the body uses glucose (pronounced: GLOO-kose), a sugar that is the body's main source of fuel. Your body needs glucose to keep running. Here's how it should work: Glucose from the food gets into your bloodstream. Your pancreas makes a hormone called insulin (pronounced: IN-suh-lin). Insulin helps the glucose get into the body's cells. The pancreas is a long, flat gland in your belly that helps your body digest food. It also makes insulin. Insulin is like a key that opens the doors to the cells of the body. It lets the glucose in. Then the glucose can move out of the blood and into the cells. But if someone has diabetes, either the body can't make insulin or the insulin doesn't work in the body like it should. The glucose can't get into the cells normally, so the blood sugar level gets too high. Lots of sugar in the blood makes people sick if they don't get treatment. There are two major types of diabetes: type 1 and type 2. Each type causes high blood sugar levels in a different way. In type 1 diabetes , the pancreas can't make insulin. The body can still get glucose from food, but the glucose can't get into the cells, where it's needed, and glucose stays in the blood. This makes the blood sugar level very high. With type 2 diabetes, the body still makes insulin. But a person with type 2 diabetes doesn't respond normally to the insulin the body makes. So glucose is less able to enter the cells and do its job of supplying energy. When glucose can't enter the cells in this way, doctors call Continue reading >>
