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How Do Insulin And Glucagon Regulate Blood Glucose Levels?

C2006/f2402 '11 Outline Of Lecture #16

C2006/f2402 '11 Outline Of Lecture #16

Handouts: 15A -- Lining of the GI Tract & Typical Circuit 15B -- Homeostasis -- Seesaw view for Glucose and Temperature Regulation; 16 -- Absorptive vs Postabsorptive state I. Homeostasis, cont. See handouts 15A & B & notes of last time, topic VI. A. Regulation of Blood Glucose Levels -- Seesaw View #1 (Handout 15B) B. Regulation of Human Body Temperature -- Seesaw #2 (Handout 15B) C. The Circuit View (Handout 15A) II. Matching circuits and signaling -- an example: How the glucose circuit works at molecular/signaling level Re-consider the circuit or seesaw diagram for homeostatic control of blood glucose levels -- what happens in the boxes on 15A? It may help to refer to the table below. A. How do Effectors Take Up Glucose? 1. Major Effectors: Liver, skeletal muscle, adipose tissue 2. Overall: In response to insulin, effectors increase both uptake & utilization of glucose. Insulin triggers one or more of the following in the effectors: a. Causes direct increase of glucose uptake by membrane transporters b. Increases breakdown of glucose to provide energy c. Increases conversion of glucose to 'stores' (1). Glucose is converted to storage forms (fat, glycogen), AND (2). Breakdown of storage fuel molecules (stores) is inhibited. d. Causes indirect increase of glucose uptake by increasing phosphorylation of glucose to G-P, trapping it inside cells 3. How does Insulin Work? a. Receptor: (1). Insulin works through a special type of cell surface receptor, a tyrosine kinase linked receptor; See Sadava fig. 7.7 (15.6). Insulin has many affects on cells and the mechanism of signal transduction is complex (activating multiple pathways). (2). In many ways, insulin acts more like a typical growth factor than like a typical endocrine. (Insulin has GF-like effects on other cells; is i Continue reading >>

The Pancreas

The Pancreas

The pancreas is an organ the upper tummy (abdomen). Chemicals (enzymes) made by cells in the pancreas pass into the gut to help digest food. The hormones insulin and glucagon are also made in the pancreas and help to regulate the blood sugar level. What is the pancreas? The pancreas is an organ which is about the size of a hand. Where is the pancreas? The pancreas is in the upper tummy (abdomen) and lies behind the stomach and guts (intestines). The pancreas has a connection via a tube (duct) to the first part of the gut (known as the duodenum) which is connected to the stomach. This connecting duct allows the chemicals (enzymes) produced by the pancreas to pass into the intestines. What does the pancreas do? The pancreas has two main functions: To make digestive chemicals (enzymes) which help us to digest food. Enzymes help to speed up your body's processes. To make hormones which regulate our metabolism. Hormones can be released into the bloodstream. They act as messengers, affecting cells and tissues in distant parts of your body. About 90% of the pancreas is dedicated to making digestive enzymes. Cells called acinar cells within the pancreas produce these enzymes. The enzymes help to make proteins, fats and carbohydrates smaller. This helps the guts (intestines) to absorb these nutrients. The acinar cells also make a liquid which creates the right conditions for pancreatic enzymes to work. This is also known as pancreatic juice. The enzymes made by the pancreas include: Pancreatic proteases (such as trypsin and chymotrypsin) - which help to digest proteins. Pancreatic amylase - which helps to digest sugars (carbohydrates). Pancreatic lipase - which helps to digest fat. Approximately 5% of the pancreas makes hormones which help to regulate your body's metabolism. The Continue reading >>

Blood Sugar Regulation

Blood Sugar Regulation

Ball-and-stick model of a glucose molecule Blood sugar regulation is the process by which the levels of blood sugar, primarily glucose, are maintained by the body within a narrow range. This tight regulation is referred to as glucose homeostasis. Insulin, which lowers blood sugar, and glucagon, which raises it, are the most well known of the hormones involved, but more recent discoveries of other glucoregulatory hormones have expanded the understanding of this process.[1] Mechanisms[edit] Blood sugar regulation the flatline is the level needed the sine wave the fluctuations. Blood sugar levels are regulated by negative feedback in order to keep the body in balance. The levels of glucose in the blood are monitored by many tissues, but the cells in the pancreatic islets are among the most well understood and important. Glucagon[edit] If the blood glucose level falls to dangerous levels (as during very heavy exercise or lack of food for extended periods), the alpha cells of the pancreas release glucagon, a hormone whose effects on liver cells act to increase blood glucose levels. They convert glycogen into glucose (this process is called glycogenolysis). The glucose is released into the bloodstream, increasing blood sugar. Hypoglycemia, the state of having low blood sugar, is treated by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods. It is often self-diagnosed and self-medicated orally by the ingestion of balanced meals. In more severe circumstances, it is treated by injection or infusion of glucagon. Insulin[edit] When levels of blood sugar rise, whether as a result of glycogen conversion, or from digestion of a meal, a different hormone is released from beta cells found in the Islets of Langerhans in the p Continue reading >>

Glucose Levels – The Effects Of Other Hormones

Glucose Levels – The Effects Of Other Hormones

Living with diabetes is hard work. Understanding the changes in your blood glucose level can be frustrating and can lead to burnout. Here’s some information that is not often discussed when the subject of blood glucose level is raised with health care professionals. There are other hormones other than insulin that affect the blood sugar levels in your body. To help you understand your blood glucose level it is important to know about glucagon, amylin, GIP, GLP-1, epinephrine, cortisol, and growth hormone. Glucagon 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. Made by islet cells (alpha cells) in the pancreas, glucagon controls the production of glucose and another fuel, ketones, in the liver. Glucagon is released overnight and between meals and is important in maintaining the body’s glucose and fuel balance. It signals the liver to break down its starch or glycogen stores and helps to form new glucose units and ketone units from other substances. It also promotes the breakdown of fat in fat cells. In contrast, after a meal, when glucose from the ingested food rushes into your bloodstream, your liver doesn’t need to make glucose. The consequence? Glucagon levels fall. In people living with diabetes the opposite occurs – while eating their glucagon levels rise, which causes the blood glucose level to rise after a meal. More about glucagon here GLP-1 & GIP GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide) and amylin are other hormones that also regulate mealtime insulin. GLP-1 and GIP are incretin hormones. When released from your gut, they signal the beta cells to increase their insulin secretion and, a Continue reading >>

Hyperglycemia In Rodent Models Of Type 2 Diabetes Requires Insulin-resistant Alpha Cells

Hyperglycemia In Rodent Models Of Type 2 Diabetes Requires Insulin-resistant Alpha Cells

Abstract To determine the role of glucagon action in diet-induced and genetic type 2 diabetes (T2D), we studied high-fat-diet–induced obese (DIO) and leptin receptor-defective (LepR−/−) rodents with and without glucagon receptors (GcgRs). DIO and LepR−/−,GcgR+/+ mice both developed hyperinsulinemia, increased liver sterol response element binding protein 1c, and obesity. DIO GcgR+/+ mice developed mild T2D, whereas LepR−/−,GcgR+/+ mice developed severe T2D. High-fat–fed (HFF) glucagon receptor-null mice did not develop hyperinsulinemia, increased liver sterol response element binding protein 1c mRNA, or obesity. Insulin treatment of HFF GcgR−/− to simulate HFF-induced hyperinsulinemia caused obesity and mild T2D. LepR−/−,GcgR−/− did not develop hyperinsulinemia or hyperglycemia. Adenoviral delivery of GcgR to GcgR−/−,LepR−/− mice caused the severe hyperinsulinemia and hyperglycemia of LepR−/− mice to appear. Spontaneous disappearance of the GcgR transgene abolished the hyperinsulinemia and hyperglycemia. In conclusion, T2D hyperglycemia requires unsuppressible hyperglucagonemia from insulin-resistant α cells and is prevented by glucagon suppression or blockade. Continue reading >>

Novel Artificial Pancreas Successfully Controls Blood Sugar More Than 24 Hours

Novel Artificial Pancreas Successfully Controls Blood Sugar More Than 24 Hours

Follow all of ScienceDaily's latest research news and top science headlines ! Novel artificial pancreas successfully controls blood sugar more than 24 hours An artificial pancreas system that closely mimics the body's blood sugar control mechanism was able to maintain near-normal glucose levels without causing hypoglycemia in a small group of patients. Depiction of the bihormonal closed-loop control system used in the clinical trial. The controller responded to venous blood glucose measured every five minutes using an FDA-approved GlucoScout (International Biomedical), and commanded insulin-glucagon control doses. The doses were administered using FDA approved Deltec CoZmo infusion pumps (Smiths Medical). Credit: Image courtesy of Massachusetts General Hospital Depiction of the bihormonal closed-loop control system used in the clinical trial. The controller responded to venous blood glucose measured every five minutes using an FDA-approved GlucoScout (International Biomedical), and commanded insulin-glucagon control doses. The doses were administered using FDA approved Deltec CoZmo infusion pumps (Smiths Medical). Credit: Image courtesy of Massachusetts General Hospital An artificial pancreas system that closely mimics the body's blood sugar control mechanism was able to maintain near-normal glucose levels without causing hypoglycemia in a small group of patients. The system, combining a blood glucose monitor and insulin pump technology with software that directs administration of insulin and the blood-sugar-raising hormone glucagon, was developed at Boston University (BU). The first clinical trial of the system was conducted at Massachusetts General Hospital (MGH) and confirmed the feasibility of an approach utilizing doses of both hormones. In their report, appearing Continue reading >>

A Whole-body Model For Glycogen Regulation Reveals A Critical Role For Substrate Cycling In Maintaining Blood Glucose Homeostasis

A Whole-body Model For Glycogen Regulation Reveals A Critical Role For Substrate Cycling In Maintaining Blood Glucose Homeostasis

Abstract Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active) and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile) cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into “whole-body” contextual models that mimic in vivo conditions. Author Summary Homeostasis of blood glucose concentrations during circadian shifts in survival-related activities, sleep and food availability is crucial for the survival of mammals. This process depends upon gluc Continue reading >>

Introduction

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 >>

Effects Of Hypoxia On Glucose, Insulin, Glucagon, And Modulation By Corticotropin-releasing Factor Receptor Type 1 In The Rat

Effects Of Hypoxia On Glucose, Insulin, Glucagon, And Modulation By Corticotropin-releasing Factor Receptor Type 1 In The Rat

Effects of Hypoxia on Glucose, Insulin, Glucagon, and Modulation by Corticotropin-Releasing Factor Receptor Type 1 in the Rat Division of Neurobiology and Physiology, College of Life Sciences and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China Address all correspondence and requests for reprints to: Dr. Xue-Qun Chen or Professor Ji-Zeng Du, Division of Neurobiology and Physiology and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China. Search for other works by this author on: Division of Neurobiology and Physiology, College of Life Sciences and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China Search for other works by this author on: Division of Neurobiology and Physiology, College of Life Sciences and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China Search for other works by this author on: Division of Neurobiology and Physiology, College of Life Sciences and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China Search for other works by this author on: Division of Neurobiology and Physiology, College of Life Sciences and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China Address all correspondence and requests for reprints to: Dr. Xue-Qun Chen or Professor Ji-Zeng Du, Division of Neurobiology and Physiology and Institute of Neuroscience, School of Medicine, Zhejiang University, Hangzhou 310058, China. Search for other works by this author on: Endocrinology, Volume 148, Issue 7, 1 July 2007, Pages 32713278, Xue-Qun Chen, Jing Dong, Chen-Ying Niu, Jun-Ming Fan, Ji-Zeng Du; Effects of Hypoxia on Glucose, Insulin, Glucagon, and Mod Continue reading >>

The Role Of The Pancreas In The Digestive (exocrine) System

The Role Of The Pancreas In The Digestive (exocrine) System

The role of the pancreas in digestion and sugar metabolism Along with the liver, the pancreas is one of the master chemists of the body. In fact, it’s two chemists in one. The pancreas is a gland about the size of a hand, tucked between a bend in the upper part of the intestines (the duodenum) and the stomach. One function of the pancreas produces enzymes for the digestive system in the exocrine tissue. The other function of the pancreas creates hormones as part of the endocrine system. Within the pancreas the tissues of both systems intertwine, which makes it difficult to treat the pancreas because things that work on one system very easily damage the other. In essence, the pancreas is a digestive organ in that all its functions relate to digestion and the regulation of nutrients entering the blood stream – especially sugar in the form of glucose. While its exocrine function connects directly to the small intestine through a system of ducts, the endocrine pancreas connects to the rest of the body through the blood and nervous systems. Both systems react to the demand for energy and the complex chemical biofeedback controlled process of digestion. The stomach breaks down the bulky food you eat and starts the process of reducing the large nutrient molecules with gastric acids. The intestines carry out the task of absorbing the nutrients into the bloodstream. The pancreas, with its ducts leading into the top of the small intestine, plays a crucial role in digestion by secreting enzymes that cut apart large nutrient molecules, making smaller molecules that can be absorbed into the bloodstream through the walls of the intestines. Within the pancreas, acinar cells produce the digestion enzymes, which travel in pancreatic juice into the duodenum through a system of ducts Continue reading >>

Blood Sugar & Other Hormones

Blood Sugar & Other Hormones

Other hormones also affect blood sugar. Glucagon, amylin, GIP, GLP-1, epinephrine, cortisol, and growth hormone also affect blood sugar levels. Glucagon: Made by islet cells (alpha cells) in the pancreas, controls the production of glucose and another fuel, ketones, in the liver. Glucagon is released overnight and between meals and is important in maintaining the body’s sugar and fuel balance. It signals the liver to break down its starch or glycogen stores and helps to form new glucose units and ketone units from other substances. It also promotes the breakdown of fat in fat cells. In contrast, after a meal, when sugar from the ingested food rushes into your bloodstream, your liver doesn’t need to make sugar. The consequence? Glucagon levels fall. Unfortunately, in individuals with diabetes, the opposite occurs. While eating, their glucagon levels rise, which causes blood sugar levels to rise after the meal. WITH DIABETES, GLUCAGON LEVELS ARE TOO HIGH AT MEALTIMES GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide) and amylin: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide) and amylin are other hormones that also regulate mealtime insulin. GLP-1 and GIP are incretin hormones. When released from your gut, they signal the beta cells to increase their insulin secretion and, at the same time, decrease the alpha cells’ release of glucagon. GLP-1 also slows down the rate at which food empties from your stomach, and it acts on the brain to make you feel full and satisfied. People with type 1 diabetes have absent or malfunctioning beta cells so the hormones insulin and amylin are missing and the hormone GLP1 cannot work properly. This may explain, in part, why individuals with diabetes do not suppress gl 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 >>

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 >>

Insulin And Glucagon: How To Manipulate Them And Lose Fat

Insulin And Glucagon: How To Manipulate Them And Lose Fat

I know many of you lean, mean, workout machine Breaking Muscle readers could care less about body fat reduction. You're already there. Your focus goes to your lift resistance amounts, improving training times, shoring up your exercise techniques, strategic planning to defeat your opponents, future competition preparation, and feeling good about your training. That's how it should be. What About Fat Loss? But guess what? There is a large segment of the population who are only concerned about shedding their "love handles.” Yes, most of these people will admit they're over-fat due to lack of physical activity and eating like it's Thanksgiving day multiple times per week. If taken to task, most people don't want to resemble an unshapely blob of protoplasm. They would rather look better, but they just don't know where to start to achieve that goal. On top of this, we all exist in a society where a plethora of high-calorie and/or low nutritional value food exists. Wise decisions must be made by all, regardless of your goals. Is it possible to eat your favorite foods, be happy, and attain your fitness goals simultaneously? Maybe. There are hundreds of diets and workout programs purportedly geared toward expunging body fat while enjoying your favorite foods. Many of them work, provided you actually adhere to their guidelines and remain disciplined with sensible calorie intake and exercise. But here’s my advice if you are attempting to maximally lose body fat: maintain your blood sugar level between 70 mg/dl and 110 mg/dl. Do this, and all other factors being equal, you will burn more fat. Biologically, it comes down to your body's innate ability to regulate two hormones - insulin and glucagon - relative to dietary intake. How Insulin and Glucagon Affect Fat Storage Insulin Continue reading >>

How Insulin And Glucagon Work To Regulate Blood Sugar Levels

How Insulin And Glucagon Work To Regulate Blood Sugar Levels

The pancreas secretes insulin and glucagon, both of which play a vital role in regulating blood sugar levels. The two hormones work in balance. If the level of one hormone is outside the ideal range, blood sugar levels may spike or drop. Together, insulin and glucagon help keep conditions inside the body steady. When blood sugar is too high, the pancreas secretes more insulin. When blood sugar levels drop, the pancreas releases glucagon to bring them back up. Blood sugar and health The body converts carbohydrates from food into sugar (glucose), which serves as a vital source of energy. Blood sugar levels vary throughout the day but, in most instances, insulin and glucagon keep these levels normal. Health factors including insulin resistance, diabetes, and problems with diet can cause a person's blood sugar levels to soar or plummet. Blood sugar levels are measured in milligrams per decilitre (mg/dl). Ideal blood sugar ranges are as follows: Before breakfast - levels should be less than 100 mg/dl for a person without diabetes and 70-130 mg/dl for a person with diabetes. Two hours after meals - levels should be less than 140 mg/dl for a person without diabetes and less than 180 mg/dl for a person with diabetes. Blood sugar regulation Blood sugar levels are a measure of how effectively an individual's body uses glucose. When the body does not convert enough glucose for use, blood sugar levels remain high. Insulin helps the body's cells absorb glucose, lowering blood sugar and providing the cells with the glucose they need for energy. When blood sugar levels are too low, the pancreas releases glucagon. Glucagon forces the liver to release stored glucose, which causes the blood sugar to rise. Insulin and glucagon are both released by islet cells in the pancreas. These cells Continue reading >>

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