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How Is Glucose Released From The Liver?

The Liver & Blood Sugar

The Liver & Blood Sugar

During a meal, your liver stores sugar for later. When you’re not eating, the liver supplies sugar by turning glycogen into glucose in a process called glycogenolysis. The liver both stores and produces sugar… The liver acts as the body’s glucose (or fuel) reservoir, and helps to keep your circulating blood sugar levels and other body fuels steady and constant. The liver both stores and manufactures glucose depending upon the body’s need. The need to store or release glucose is primarily signaled by the hormones insulin and glucagon. During a meal, your liver will store sugar, or glucose, as glycogen for a later time when your body needs it. The high levels of insulin and suppressed levels of glucagon during a meal promote the storage of glucose as glycogen. The liver makes sugar when you need it…. When you’re not eating – especially overnight or between meals, the body has to make its own sugar. The liver supplies sugar or glucose by turning glycogen into glucose in a process called glycogenolysis. The liver also can manufacture necessary sugar or glucose by harvesting amino acids, waste products and fat byproducts. This process is called gluconeogenesis. When your body’s glycogen storage is running low, the body starts to conserve the sugar supplies for the organs that always require sugar. These include: the brain, red blood cells and parts of the kidney. To supplement the limited sugar supply, the liver makes alternative fuels called ketones from fats. This process is called ketogenesis. The hormone signal for ketogenesis to begin is a low level of insulin. Ketones are burned as fuel by muscle and other body organs. And the sugar is saved for the organs that need it. The terms “gluconeogenesis, glycogenolysis and ketogenesis” may seem like compli Continue reading >>

You And Your Hormones

You And Your Hormones

What is glucagon? Glucagon is a hormone that is involved in controlling blood sugar (glucose) levels. It is secreted into the bloodstream by the alpha cells, found in the islets of langerhans, in the pancreas. The glucagon-secreting alpha cells surround a core of insulin-secreting beta cells, which reflects the close relationship between the two hormones. Glucagon’s role in the body is to prevent blood glucose levels dropping too low. To do this, it acts on the liver in several ways: It stimulates the conversion of stored glycogen (stored in the liver) to glucose, which can be released into the bloodstream. This process is called glycogenolysis. It promotes the production of glucose from amino acid molecules. This process is called gluconeogenesis. It reduces glucose consumption by the liver so that as much glucose as possible can be secreted into the bloodstream to maintain blood glucose levels. Glucagon also acts on adipose tissue to stimulate the breakdown of fat stores into the bloodstream. How is glucagon controlled? Glucagon works along with the hormone insulin to control blood sugar levels and keep them within set levels. Glucagon is released to stop blood sugar levels dropping too low, while insulin is released to stop blood sugar levels rising too high. Release of glucagon is stimulated by low blood glucose (hypoglycaemia), protein-rich meals and adrenaline (another important hormone for combating low glucose). Release of glucagon is prevented by raised blood glucose and carbohydrate in meals, detected by cells in the pancreas. In the longer-term, glucagon is crucial to the body’s response to lack of food. For example, it encourages the use of stored fat for energy in order to preserve the limited supply of glucose. What happens if I have too much glucagon? Continue reading >>

Energy Metabolism In The Liver

Energy Metabolism In The Liver

Go to: Introduction The liver is a key metabolic organ which governs body energy metabolism. It acts as a hub to metabolically connect to various tissues, including skeletal muscle and adipose tissue. Food is digested in the gastrointestinal (GI) tract, and glucose, fatty acids, and amino acids are absorbed into the bloodstream and transported to the liver through the portal vein circulation system. In the postprandial state, glucose is condensed into glycogen and/or converted into fatty acids or amino acids in the liver. In hepatocytes, free fatty acids are esterified with glycerol-3-phosphate to generate triacylglycerol (TAG). TAG is stored in lipid droplets in hepatocytes or secreted into the circulation as very low-density lipoprotein (VLDL) particles. Amino acids are metabolized to provide energy or used to synthesize proteins, glucose, and/or other bioactive molecules. In the fasted state or during exercise, fuel substrates (e.g. glucose and TAG) are released from the liver into the circulation and metabolized by muscle, adipose tissue, and other extrahepatic tissues. Adipose tissue produces and releases nonesterified fatty acids (NEFAs) and glycerol via lipolysis. Muscle breaks down glycogen and proteins and releases lactate and alanine. Alanine, lactate, and glycerol are delivered to the liver and used as precursors to synthesize glucose (gluconeogenesis). NEFAs are oxidized in hepatic mitochondria through fatty acid β oxidation and generate ketone bodies (ketogenesis). Liver-generated glucose and ketone bodies provide essential metabolic fuels for extrahepatic tissues during starvation and exercise. Liver energy metabolism is tightly controlled. Multiple nutrient, hormonal, and neuronal signals have been identified to regulate glucose, lipid, and amino acid me Continue reading >>

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 >>

Regulation Of Glucose Production By The Liver.

Regulation Of Glucose Production By The Liver.

Abstract Glucose is an essential nutrient for the human body. It is the major energy source for many cells, which depend on the bloodstream for a steady supply. Blood glucose levels, therefore, are carefully maintained. The liver plays a central role in this process by balancing the uptake and storage of glucose via glycogenesis and the release of glucose via glycogenolysis and gluconeogenesis. The several substrate cycles in the major metabolic pathways of the liver play key roles in the regulation of glucose production. In this review, we focus on the short- and long-term regulation glucose-6-phosphatase and its substrate cycle counter-part, glucokinase. The substrate cycle enzyme glucose-6-phosphatase catalyzes the terminal step in both the gluconeogenic and glycogenolytic pathways and is opposed by the glycolytic enzyme glucokinase. In addition, we include the regulation of GLUT 2, which facilitates the final step in the transport of glucose out of the liver and into the bloodstream. Continue reading >>

Why Diabetics Over Produce Sugar In The Liver

Why Diabetics Over Produce Sugar In The Liver

Why Diabetics Over Produce Sugar in the Liver Type 2 diabetics often suffer from an over-production of sugar within the liver, a response to falling blood glucose levels. This potentially dangerous mechanism was poorly understood until recently, when researchers uncovered the role that a certain master regulator plays in sugar production within the liver. While an inability to regulate blood glucose levels, due to resistance to insulin produced by pancreatic beta cells, is the primary mechanism that leads to and enhances type 2 diabetes, the liver plays a large role as well. Beta-cells, in a healthy body, produce insulin, which helps regulate blood glucose levels, but the liver itself directly responds to low blood glucose levels by producing more sugar. In type 2 diabetics, who suffer from insulin resistance (and therefore dysfunctional regulation of blood glucose with insulin), the liver often has a tendency to produce sugar when not really needed, which can cause potential harm. In other words, the liver continues to produce sugar past what it should, because insulin is not regulating the sugar already being produced, in type 2 diabetics. To illustrate the role that the liver plays in type 2 diabetics, researcher Dr. Jenny Gunton explains that over-production of sugar within the liver is why many diabetics wake up with higher blood glucose levels than they had when going to sleep: It upsets people when their blood sugar behaves as if theyre getting up in the night and having a really big snack. I have to tell them its just one of those unfair things about having diabetes. Researchers looked at ARNT, a so-called master regulator, which is known to play a large role in insulin production and blood glucose control. Past research by the same research team demonstrated t Continue reading >>

Sugar Production Switch In Liver May Offer Target For New Diabetes Therapies

Sugar Production Switch In Liver May Offer Target For New Diabetes Therapies

Sugar production switch in liver may offer target for new diabetes therapies Salk researchers find molecular switch that controls liver glucose production and may represent a new avenue for treating insulin-resistant type II diabetes LA JOLLA, CA—In their extraordinary quest to decode human metabolism, researchers at the Salk Institute for Biological Studies have discovered a pair of molecules that regulates the liver’s production of glucose—the simple sugar that is the source of energy in human cells and the central player in diabetes. In a paper published April 8 in Nature, the scientists say that controlling the activity of these two molecules—which work together to allow more or less glucose production—could potentially offer a new way to lower blood sugar to treat insulin-resistant type II diabetes. They showed, through an experimental technique, that this was possible in diabetic mice. “If you control these switches, you can control the production of glucose, which is really at the heart of the problem of type 2 diabetes,” says Professor Marc Montminy, head of Salk’s Clayton Foundation Laboratories for Peptide Biology. The need for new drugs is accelerating, says Montminy, as almost 26 million Americans have type II diabetes, and an estimated 79 million people are at risk of developing the condition. Diabetes is the sixth leading cause of death in the United States, and treatment costs are estimated at $116 billion annually. In order to develop new and effective treatments for diabetes, researchers need to understand the complex and delicate biology behind human metabolism as well as the disorders that develop when this finely tuned system is out of balance, Montminy says. During the day, humans burn glucose, derived from the food we eat. This is t Continue reading >>

How Does The Liver Control Glucose In The Blood?

How Does The Liver Control Glucose In The Blood?

Your body needs a constant supply of glucose, or sugar, for cells to have energy, so it requires a readily available reservoir to keep blood glucose in balance. One of the liver’s main roles in the body is controlling the amount of glucose circulating in the blood. By storing excess glucose as glycogen and creating new glucose from proteins and fat byproducts, the liver is able to maintain balanced glucose levels in your body at all times. Video of the Day When you eat carbohydrates, the body releases glucose into the bloodstream immediately, triggering the production of insulin. The body cannot be in a state of constant consumption, so when insulin levels are high enough, the body links long chains of glucose together into a compound called glycogen, which is then stored in the liver and the muscles. The liver uses this stored glucose energy as its main reservoir for releasing glucose into the bloodstream when levels drop. Breakdown of Glycogen Blood glucose levels drop when you're not eating, such as during sleep or between meals. This low blood sugar signals the liver to produce glucose and release it back into the bloodstream. The liver favors glycogen as its primary source since it is efficiently broken down into glucose in a process known as glycogenolysis. In this process, the liver breaks the bonds that hold glucose molecules together as glycogen, degrading most but not all of the glycogen molecule. Effects of Insulin Resistance When your body is chronically subjected to high levels of blood sugar and insulin, such as after you've eaten an excessive amount of foods high in sugar, it develops a resistance to the hormone, and the liver cannot respond properly, eventually leading to type-2 diabetes if the resistance is not controlled. According to a study publish 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 >>

The Liver And Blood Glucose Levels

The Liver And Blood Glucose Levels

Tweet Glucose is the key source of energy for the human body. Supply of this vital nutrient is carried through the bloodstream to many of the body’s cells. The liver produces, stores and releases glucose depending on the body’s need for glucose, a monosaccharide. This is primarily indicated by the hormones insulin - the main regulator of sugar in the blood - and glucagon. In fact, the liver acts as the body’s glucose reservoir and helps to keep your circulating blood sugar levels and other body fuels steady and constant. How the liver regulates blood glucose During absorption and digestion, the carbohydrates in the food you eat are reduced to their simplest form, glucose. Excess glucose is then removed from the blood, with the majority of it being converted into glycogen, the storage form of glucose, by the liver’s hepatic cells via a process called glycogenesis. Glycogenolysis When blood glucose concentration declines, the liver initiates glycogenolysis. The hepatic cells reconvert their glycogen stores into glucose, and continually release them into the blood until levels approach normal range. However, when blood glucose levels fall during a long fast, the body’s glycogen stores dwindle and additional sources of blood sugar are required. To help make up this shortfall, the liver, along with the kidneys, uses amino acids, lactic acid and glycerol to produce glucose. This process is known as gluconeogenesis. The liver may also convert other sugars such as sucrose, fructose, and galactose into glucose if your body’s glucose needs not being met by your diet. Ketones Ketones are alternative fuels that are produced by the liver from fats when sugar is in short supply. When your body’s glycogen storage runs low, the body starts conserving the sugar supplies fo 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 >>

Liver Fat Gets A Wake-up Call That Maintains Blood Sugar Levels, According To Penn Study

Liver Fat Gets A Wake-up Call That Maintains Blood Sugar Levels, According To Penn Study

A Penn research team, led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania, reports in Nature Medicine that mice in which an enzyme called histone deacetylase 3 (HDAC3) was deleted had massively fatty livers, but lower blood sugar, and were thus protected from glucose intolerance and insulin resistance, the hallmark of diabetes. High-fat-diet (HFD)-induced fatty liver in wild-type mice, characterized by big lipid droplets in liver cells (top). Liver-specific HDAC3 knockout mice on HFD, note that the lipid droplets become smaller even though the total lipid content is increased (bottom). Credit: Mitchell Lazar, M.D., Ph.D.; Zheng Sun, Ph.D., Perelman School of Medicine, University of Pennsylvania; Nature Medicine Insulin resistance occurs when the body does a poor job of lowering blood sugars. Typically, patients with obesity and type 2 diabetes have fatty livers, and the dogma in the field, says Lazar, is that the fatty livers contribute to the insulin resistance and diabetes in a vicious cycle. These findings are "a clear counterexample to this thinking," he says. The researchers observed that the extra fat in the liver did not cause insulin resistance because it was sequestered in tiny lipid droplets inside individual liver cells, coated by a specific protein. The metabolites that would otherwise be used by the body to make glucose were re-routed to make fat, leading to reduced glucose in the bloodstream. The advantage of the lower blood sugar is tempered by the excess liver fat, which can lead to problems of its own, including liver failure. Cells of high-fat-diet-induced fatty livers in wild-type mice were characterized by larger lipid droplets, but liver-specif 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 >>

How Sugar Messes Up Your Liver And Gives You Diabetes

How Sugar Messes Up Your Liver And Gives You Diabetes

Modern man is plagued with many diseases that you will not find in some "primitive" populations like modern hunter-gatherers. These include obesity, heart disease, some cancers and last but not least, type II diabetes... which has reached epidemic proportions in the past few decades and now afflicts about 300 million people worldwide. This disease is a common cause of early death, blindness, amputation and a severely decreased quality of life... and it is advancing rapidly, every single year. In the video above, Dr. Robert H. Lustig and Dr. Elissa S. Epel explain how excess sugar can mess up liver metabolism and ultimately lead to diabetes. Dr. Lustig recently took part in a study where they examined the associations between sugar consumption and diabetes in 175 countries (1). They found very clear associations, where each 150 kcal (about one can of soda) per day of sugar increased the prevalence of diabetes by 1.1%. To put this number in perspective, if all of the U.S. added one can of soda to their daily diet, almost 3.5 million more people would become diabetic. In this study, added sugar was the only part of the diet that correlated with diabetes when they adjusted for confounding factors. These types of studies are so-called observational studies, which can not prove that one thing caused another, it can only show that they are correlated. However, there are other lines of evidence linking sugar to the development of type II diabetes and this specifically involves how sugar affects the liver. Sugar is composed of two molecules... glucose and fructose. Glucose can be metabolized by every cell in the body and if we don't get it from the diet, our bodies make it. However, fructose is different. The only organ that can metabolize sugar is the liver, because only the li Continue reading >>

Healing Leaky Livers

Healing Leaky Livers

It may surprise you to know that, for many people, Type 2 diabetes is primarily a liver disease. The pancreas damage comes later. Is there anything we can do to heal a diabetic liver? Liver issues in diabetes are complicated. An article in the journal Clinical Diabetes explained that diabetes can cause liver disease; liver disease can cause diabetes; or both can arise together from other causes. Whichever comes first, the sick liver may produce way too much glucose, enough to overwhelm the body’s insulin. Why would a liver start pumping out unneeded glucose? Unhealthy livers tend to have a lot of fat in them, a condition called nonalcoholic fatty liver disease, or NAFLD. You don’t have to be fat to have a fatty liver (although overweight and obesity are risk factors). Thin people get it too, and the causes of NAFLD are unknown. Some are thought to be genetic. However, a recent animal study published in the journal PLOS One found that prenatal exposure to alcohol (from a mother who drank while pregnant) is strongly associated diabetes-like glucose production by the liver. There are probably other causes as well, including environmental chemicals and possibly unhealthy diets. A rat study in the Journal of Biological Chemistry found that fatty livers became more resistant to insulin. The researchers found processes by which insulin normally tells the liver to stop producing unwanted glucose. Excess fat in the liver seemed to block these processes, so too much glucose was produced. Human livers apparently act the same way. An Italian study in The American Journal of Medicine found that subjects with NAFLD had high fasting and postmeal insulin levels, high insulin resistance, and high triglyceride levels. (Triglycerides are a kind of blood fat.) High insulin levels can b Continue reading >>

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