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What Does Glucagon Do In Diabetes?

The Role Of Glucagon On Type 2 Diabetes At A Glance

The Role Of Glucagon On Type 2 Diabetes At A Glance

Abstract The opposite effects of insulin and glucagon in fuel homeostasis, the paracrine/endocrine inhibitory effects of insulin on glucagon secretion and the hyperglucagonemia in the pathogenesis of type 2 diabetes (T2D) have long been recognized. Inappropriately increased alpha-cell function importantly contributes to hyperglycemia and reflects the loss of tonic restraint normally exerted by high local concentrations of insulin on alpha-cells, possibly as a result of beta-cell failure and alpha-cell insulin resistance, but additional mechanisms, such as the participation of incretin hormones in this response, have also been suggested. Three classes of drugs already available for clinical use address the abnormalities of glucagon secretion in T2D, namely, the GLP-1 receptor agonists (GLP-1RA), the inhibitors of dipeptidyl peptidase-4 (DPP-4i) and the amylin agonist pramlintide; it has been proposed that the glucagonostatic and insulinotropic effects of GLP-1RA equally contribute to their hypoglycemic efficacy. In this review, the control of glucagon secretion and its participation in T2D pathogenesis are summarized. The main players in the control of glucagon secretion The existence of glucagon was suggested by Murlin et al. [1] in 1923, right after insulin discovery, to explain the precocious hyperglycemic effect of pancreatic extracts, which, according to their hypothesis, was contaminated with a GLUCose AGONist substance. In 1948, Sutherland and de Duve [2] defined the alpha-cells of the islets of Langerhans as the source of glucagon as well as the actions of this hormone stimulating hepatic glycogenolysis and gluconeogenesis in hypoglycemic conditions. In 1959, Unger et al. [3] reported a glucagon radioimmunoassay. Insulin and glucagon participate in fuel homeostas Continue reading >>

Glucagon

Glucagon

This article is about the natural hormone. For the medication, see Glucagon (medication). Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose and fat in the bloodstream, and is considered to be the main catabolic hormone of the body [3]. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers the extracellular glucose.[4] The pancreas releases glucagon when the concentration of glucose in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream.[5] High blood-glucose levels, on the other hand, stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin-dependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. Glucagon increases energy expenditure and is elevated under conditions of stress.[6] Glucagon belongs to the secritin family of hormones. Function[edit] Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis [7]. Glucagon also decreases fatty acid synthesis in adipose tissue and the liver, as well as promoting lipolysis in these tissues, which causes them to release fatty acids into circulation where they can be catabolised to generate energy in tissues such as skeletal muscle when required [8]. Glucose is stored in the liver in the form of the polysaccharide glycogen, which is a glucan (a polymer made up of glucose molecules). Liver cells (hepatocytes) have glucagon receptors. When glucagon binds to the glucagon receptors, the liver cells convert the glycogen into individual glucose molecules and re 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 >>

Why Everyone Is Talking About Glucagon

Why Everyone Is Talking About Glucagon

The most famous of diabetes hormones may be insulin, but at the American Diabetes Association’s Scientific Sessions this year in Chicago, the hot topic was a different hormone: glucagon. From the talks to the exhibit hall to the after-parties, the buzz went glucagon glucagon glucagon. Why? Isn’t glucagon just a powder in a kit used to rescue diabetics passed out from hypoglycemia? Up until recently, glucagon was only discussed as a rarely used rescue treatment for diabetics. However, glucagon is now gaining attention as the yin to insulin’s yang, and a hormone that could be beneficial for daily glucose management, and that may be necessary for a closed-loop artificial pancreas system. What is Glucagon? But before we jump to the question of why glucagon, we should start with what glucagon is [1]. Like insulin, glucagon is a hormone produced by the cells of the pancreas. Insulin is produced by the beta cells, and glucagon is produced by the nearby alpha cells. Whereas insulin’s net effect is to allow cells of the body to take glucose out of the blood, lowering blood glucose levels, glucagon has the opposite effect. Glucagon’s main site of activity is the liver, as it induces the liver to convert stored glycogen into glucose and release the glucose into the bloodstream, thereby increasing blood glucose levels. In a normal, non-diabetic person, increased sugar intake causes the beta cells to release insulin. The blood vessels supplying the beta cells carry that insulin as they pass the alpha cells. The alpha cells interpret signals passed from the upstream beta cells, and repress their glucagon production while the beta cells are working to lower blood sugar levels. However, as blood sugar levels drop, and the beta cells stop releasing insulin, the alpha cells are Continue reading >>

Minireview: Glucagon In The Pathogenesis Of Hypoglycemia And Hyperglycemia In Diabetes

Minireview: Glucagon In The Pathogenesis Of Hypoglycemia And Hyperglycemia In Diabetes

Minireview: Glucagon in the Pathogenesis of Hypoglycemia and Hyperglycemia in Diabetes Division of Endocrinology, Metabolism, and Lipid Research, Washington University, St. Louis, Missouri 63110 Address all correspondence and requests for reprints to: Philip E. Cryer, M.D., Campus Box 8127, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110. Search for other works by this author on: Endocrinology, Volume 153, Issue 3, 1 March 2012, Pages 10391048, Philip E. Cryer; Minireview: Glucagon in the Pathogenesis of Hypoglycemia and Hyperglycemia in Diabetes, Endocrinology, Volume 153, Issue 3, 1 March 2012, Pages 10391048, Pancreatic islet -cell glucagon secretion is critically dependent on pancreatic islet -cell insulin secretion. Normally, a decrease in the plasma glucose concentration causes a decrease in -cell insulin secretion that signals an increase in -cell glucagon secretion during hypoglycemia. In contrast, an increase in the plasma glucose concentration, among other stimuli, causes an increase in -cell insulin secretion that signals a decrease, or at least no change, in -cell glucagon secretion after a meal. In absolute endogenous insulin deficiency (i.e. in type 1 diabetes and in advanced type 2 diabetes), however, -cell failure results in no decrease in -cell insulin secretion and thus no increase in -cell glucagon secretion during hypoglycemia and no increase in -cell insulin secretion and thus an increase in -cell glucagon secretion after a meal. In type 1 diabetes and advanced type 2 diabetes, the absence of an increment in glucagon secretion, in the setting of an absent decrement in insulin secretion and an attenuated increment in sympathoadrenal activity, in response to falling plasma glucose concentrations plays a ke Continue reading >>

Understanding Glucagon In People With Diabetes

Understanding Glucagon In People With Diabetes

Glucagon Kit for Severe Hypoglycemia Emergencies Most of us understand the importance of insulin in controlling our blood glucose (BG) levels. When our BG levels get too high, we can bring them down by injecting insulin. Insulin is made in and secreted by the beta cells in the pancreas. Many of us are also aware that another hormone,glucagon, helps bring BG levels up when they get too low. Glucagon is made in and secreted by the alpha cells in the pancreas. In nondiabetics and people with type 2 diabetes or early type 1 diabetes, glucagon automatically gets secreted when BG levels get too low. But people with longstanding type 1 diabetes often stop producing much glucagon and need glucagon shots to bring up a serious low. (If you don’t currently have an emergency glucagon kit, ask your doctor for a prescription and review the directions with your family so they know how to administer it for you during severe hypoglycemia.) Insulin and glucagon are like the accelerator and brake on your car. And it’s the ratio of the two, rather than the absolute amount, that is important. If you have almost no insulin, you might be able to have normal BG levels if you also had almost no glucagon. In fact, a study done in 1981 in a man who had no pancreas, showed that BG levels could be maintained at about 100 without insulin as long as they didn’t give the man glucagon. The problem is that when the beta cells give out, the alpha cells don’t give out as well. In fact, they often secrete even more glucagon than they would in a nondiabetic. Glucagon tells the liver to produce and secrete glucose, so the BG levels stay high even when you don’t eat. Most diabetes researchers focus on beta cells and insulin production, but some are studying the alpha cells and glucagon production as Continue reading >>

Glucagon As A Critical Factor In The Pathology Of Diabetes

Glucagon As A Critical Factor In The Pathology Of Diabetes

Studies from the laboratory of Roger Unger presented in the current issue of Diabetes highlight the potential benefit of reducing glucagon action by examining the effects of glucagon receptor knockout (Gcgr−/−) on the phenotype of type 1 diabetes in the mouse (1). The aim of the study was to determine if glucagon action, by itself, causes the lethal consequences of insulin deficiency. Because treatment of Gcgr−/− mice with the β-cell toxin streptozotocin (STZ) previously had no effect on circulating insulin levels or pancreatic islet architecture (2), Lee et al. (1) administered a double dose of STZ to maximize β-cell destruction. Unlike STZ treated wild-type Gcgr+/+ mice, which became severely hyperglycemic, STZ-treated mice lacking glucagon signaling appeared to be in a normal state of health and were completely protected from the manifestations of diabetes (1), as shown previously by the same group in alloxan treated Gcgr−/− mice (3) and by Hancock et al. (4) in STZ-treated mice lacking glucagon because of α-cell deletion. Fasting hyperglycemia did not occur in STZ-treated Gcgr−/− mice, and astonishingly, the animals demonstrated normal or even improved glucose disposal in response to a glucose tolerance test, despite the absence of a rise in plasma insulin. These results led the authors to speculate that insulin action during glucose absorption is largely directed toward overcoming the hepatic actions of glucagon. They theorized that insulin would have little or no role in a liver not exposed to the action of glucagon because it would be in a permanent glucose storage mode. Glucagon antagonistic peptides, neutralizing antibodies, receptor antisense oligonucleotides, and/or receptor nonpeptidyl antagonists have previously been shown to lower plasma 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 >>

Glucagon: What It Is, And How To Use It

Glucagon: What It Is, And How To Use It

Print When a person has type 1 diabetes, this doesn’t happen. People with type 1 diabetes must check their blood sugar regularly, try to prevent low blood sugar, and treat it as soon as it happens with a source of fast-acting sugar (like juice, candy, or a soft drink). If a person’s blood sugar drops so low that they are unable to treat it themselves, they are having a severe low blood sugar (severe hypoglycemia). Other symptoms include: Being unresponsive or unconscious Having a seizure Being so uncooperative that you can’t give juice or sugar by mouth Note: Severe low blood sugar is an emergency. You must act immediately. Do not leave the student alone. Carefully following a student’s Individual Care Plan should help to prevent a severe low blood sugar from happening at school. But it’s important to know what to do in case of emergency. What to do for severe low blood sugar Place the student in recovery position. Have someone call 911. Then call the student’s parents. Stay with the student until ambulance arrives. Do not put anything in their mouth, such as food or drink (choking hazard). If there is a signed consent and mutual agreement to give glucagon (usually in the student’s Individual Care Plan), give it now. Staff identified in the care plan to give glucagon will have been trained. How to use glucagon Dose Students 5 years old and younger: 0.5 mg = 0.5 mL Students 6 years and older: 1.0 mg = 1.0 mL Preparing and giving glucagon Remove cap from vial (bottle) of powder Remove needle protector from syringe and insert the needle all the way into the vial Inject liquid from syringe into dry powder bottle Roll the bottle gently to dissolve powder. The solution will be clear. Draw the fluid (see above for dose) back into the syringe Inject into outer mid Continue reading >>

What Is Glucagon?

What Is Glucagon?

Tweet The effects of glucagon are the opposite of the effects induced by insulin. The two hormones need to work in partnership with each other to keep blood glucose levels balanced. Glucagon is a hormone that is produced by alpha cells in a part of the pancreas known as the islets of Langerhans. The role of glucagon in the body Glucagon plays an active role in allowing the body to regulate the utilisation of glucose and fats. Glucagon is released in response to low blood glucose levels and to events whereby the body needs additional glucose, such as in response to vigorous exercise. When glucagon is released it can perform the following tasks: Stimulating the liver to break down glycogen to be released into the blood as glucose Activating gluconeogenesis, the conversion of amino acids into glucose Breaking down stored fat (triglycerides) into fatty acids for use as fuel by cells Glucagon and blood glucose levels Glucagon serves to keep blood glucose levels high enough for the body to function well. When blood glucose levels are low, glucagon is released and signals the liver to release glucose into the blood. Glucagon secretion in response to meals varies depending on what we eat: In response to a carbohydrate based meal, glucagon levels in the blood fall to prevent blood glucose rising too high. In response to a high protein meal, glucagon levels in the blood rise. Glucagon in diabetes In people with diabetes, glucagon’s presence can raise blood glucose levels too high. The reason for this is either because not enough insulin is present or, as is the case in type 2 diabetes, the body is less able to respond to insulin. In type 1 diabetes, high levels of circulating insulin can inhibit the release of glucagon in response to hypoglycemia. Medications which affect gluca Continue reading >>

Glucagon: How The Hormone Affects Blood Sugar

Glucagon: How The Hormone Affects Blood Sugar

Changes in your blood sugar levels can affect how you feel. To help you keep the level steady and healthy, your body makes a hormone called glucagon while you sleep and after you eat. It's made in your pancreas, a small organ above your liver, and it can raise levels of glucose, or sugar, in your blood. That's the fuel your muscles and organs use to work and stay healthy. Glucagon helps your liver break down the food you eat to make glucose. If your blood sugar drops too low, you can get hypoglycemia. This can make you feel dizzy or sluggish or even pass out. Glucagon can help with hypoglycemia so you feel right again. Glucagon works with your liver to turn a type of stored sugar called glycogen into glucose. Glucose goes from your liver into your blood to give you energy. Glucagon can tell your liver not to take in too much glucose from the food you eat and to release stored sugar into your blood instead. This can keep your glucose levels steady. If your blood sugar dips too low, your pancreas releases glucagon to tell your liver to make more glucose. Glucagon can also play a role in how amino acids (compounds that help make up muscles and tissue in your body) make glucose. And it can break down triglycerides, or fat your body stores, into fuel. Glucagon and insulin, another kind of hormone, should work as a team to keep your blood sugar in balance. The cells in your pancreas that make glucagon are similar to cells that make insulin. Your body needs it to turn blood sugar into fuel. If you have diabetes, your body either doesn't make insulin or doesn't make enough. This can change how your body makes glucagon. Usually, food gives your body the sugar and energy it needs. Glucagon levels then go down because your liver doesn't need to make more sugar to fuel your muscles Continue reading >>

What Does Glucagon Do?

What Does Glucagon Do?

ANSWER Changes in your blood sugar levels can affect how you feel. To help you keep blood sugar levels steady and healthy, your body makes a hormone called glucagon while you sleep and after you eat. It's made in your pancreas, a small organ above your liver, and it can raise levels of glucose, or sugar, in your blood. That's the fuel your muscles and organs use to work and stay healthy. Glucagon helps your liver break down the food you eat to make glucose. Continue reading >>

Glucagon-injection, Glucagon

Glucagon-injection, Glucagon

GLUCAGON-INJECTION, Glucagon GENERIC NAME: GLUCAGON - INJECTION (GLUE-kuh-gone) BRAND NAME(S): Glucagon USES: Glucagon is a hormone that causes the liver to release glucose into the blood. It is used to quickly increase blood sugar levels in diabetics with low blood sugar (hypoglycemia). This medication may also be used during certain medical tests. HOW TO USE: This medication is given as an injection either into a vein, an arm or leg muscle or under the skin as directed. The glucagon powder must first be dissolved using the diluting fluid provided. Use this medication immediately after it has been mixed. Unconscious patients usually return to consciousness within 5 to 20 minutes of receiving glucagon. Notify your doctor when a hypoglycemic episode has occurred so your insulin dose and diet may be adjusted if necessary. Closely monitor your blood sugar level to prevent it from getting too low. When used as a part of a medical test/procedure, you should be given sugar replacement immediately following the test to prevent low blood sugar. Diabetes Diet: Healthy Meal Plans for Diabetes-Friendly Eating SIDE EFFECTS: Nausea and vomiting may occur but are also signs of low blood sugar. Allergy symptoms such as skin rash and breathing trouble have been reported with this medication. Inform your doctor if you experience any of these effects. If you notice other effects not listed above, contact your doctor or pharmacist. PRECAUTIONS: All patients with diabetes should have a glucagon emergency kit available. Friends and relatives of a diabetic patient should know the symptoms of hypoglycemia and be instructed how to administer glucagon if necessary. Detailed patient instructions are provided with the medication. Be sure to read them completely and ask your doctor or pharmacist a Continue reading >>

Glucagon

Glucagon

A counterregulatory hormone that works against the action of insulin. Most people with diabetes know that insulin is secreted by the beta cells of the pancreas. What many don’t know is that other cells in the pancreas called alpha cells secrete the hormone glucagon. Glucagon is one of the counterregulatory hormones that helps the body regulate blood glucose levels. In people who don’t have diabetes, when blood glucose levels fall, the beta cells secrete less insulin. In addition, the alpha cells secrete more glucagon. Glucagon prods the liver to convert more of its stored glycogen into glucose, which it secretes into the bloodstream, raising blood sugar levels. People with Type 1 diabetes no longer secrete insulin and therefore cannot change their insulin levels to respond to changes in blood glucose levels. To make matters worse, some of them lose the ability to secrete glucagon in response to low blood sugar, making them especially prone to severe hypoglycemia. Fortunately, glucagon is available in pharmacies in the form of the Glucagon Emergency Kit, which everyone with Type 1 diabetes ought to have on hand for treating severe hypoglycemia. When people with diabetes are unconscious or too confused to consume a food or drink containing carbohydrate, a friend or family member can inject the glucagon, which can restore the blood glucose level to normal within 5 or 10 minutes. The kit comes with a syringe containing an inert solution, a vial of crystallized glucagon, and a set of instructions—which potential users should plan to read before the kit is needed. The user injects the solution into the vial, shakes it up to dissolve the glucagon crystals, draws the solution back into the syringe, and injects it under the skin or into a muscle. In some people, glucagon c Continue reading >>

Glucagon

Glucagon

Editors Note:This content has been verified byMarina Basina, MD, a Clinical Associate Professor at Stanford University. Shes a clinical endocrinologist and researcher with a focus on diabetes management and diabetes technology. Dr. Basina is an active member of multiple medical advisory boards and community diabetes organizations, and she is on the Beyond Type 1 Science Advisory Council. Besides being a hormone that occurs naturally in the body, glucagon is also an emergency medicine used when a person with diabetes is experiencing hypoglycemia and cannot take sugar orally or in non-emergency situations with mini-dosing to prevent glycemic overshoot. It comes in powder form and must be added to a solution in order to administer it. Once injected, it raises the blood sugar by sending a signal to the muscles and liver (where glucose is stored in your body).The effect of glucagon is opposite of the effect of insulin, raising blood sugar instead of lowering it. What is the difference between glucagon and insulin? In people with a fully functional pancreas, insulin and glucagon work in tandem to keep blood sugars stable. Insulin lowers blood sugar, while its partner, glucagon, releases the bodys glucose reserves from the liver to raise blood sugars. If you are conscious but cannot consume sugar orally, you can self-administer glucagon. If you are unconscious, someone else will need to inject the glucagon into muscle. If hospitalized, the injection may be given intravenously. Always contact emergency services if glucagon is administered in an emergency situation. In cases of hypoglycemia (low blood sugar), glucagon allows the body to release sugar into the blood stream, so BGLs elevate to a safer range. Consult a physician to see if it would be helpful to use glucagon in gly Continue reading >>

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