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Liver Glucose

Role Of Liver In Glucose Homeostasis

Role Of Liver In Glucose Homeostasis

The liver has a unique role in regulation of blood glucose in the postabsorptive state, after ingestion of glucose-containing meals, and in circumstances of glucopenia. It is soley responsible for the delivery of glucose to the bloodstream in the fasted state, thereby maintaining blood glucose concentration for the ongoing needs of body tissues, particularly the brain. An equally important role is played by the liver in the maintenance of normal glucose tolerance in response to carbohydrate ingestion. The liver is the principal site of glucose deposition after glucose feeding, while muscle and adipose tissue represent relatively minor sites of disposal of ingested glucose. In addition, the rise in glucose and insulin caused by glucose ingestion inhibits endogenous hepatic glucose production, which serves to minimize postprandial elevations in blood glucose. When blood glucose is reduced by small increments in circulating insulin, a rebound increase in glucose output from the liver is the initial or principal mechanism counteracting the fall in blood glucose concentration. Studies in juvenile-onset diabetes indicate that the liver is capable of altering its release of glucose in response to changes in blood glucose concentration when small, physiologic doses of insulin are infused. These findings may provide an explanation for the efficacy of preprogrammed insulin delivery systems in the treatment of diabetes. Several insulin models are examined as to their responses to various insulin inputs and glucose utilization and production control. It is shown that the action of insulin on glucose utilization correlates best with model compartments having a 30–50-min delay compared with plasma, whereas glucose production control is rapid. It is further shown that whereas the pr Continue reading >>

Hepatic Glucose And Fatty Acid Metabolism | Benthamscience

Hepatic Glucose And Fatty Acid Metabolism | Benthamscience

Hepatic Glucose and Fatty Acid Metabolism The liver is a vital organ involved in the preservation of the balance among the metabolicfunctions of the whole-body. Liver metabolism is complex and most difficult to investigate or tomonitor, and only indirect measurements have been available in human beings for a long time. This isdue to the peculiar anatomical location of the liver, since circulating substrates reach the organ via thehepatic artery and the portal vein, the latter being not accessible for routine measurements. Recently,PET imaging has been introduced to characterize liver glucose and fatty acid metabolism. Mathematicalmodelling of liver metabolism by use of PET and [18F]fluoro-2-deoxy-D-glucose (18F-FDG) or[11C]Palmitate (11C-palmitate) has been recently validated, and the requirement of a dual (arterial andportal venous) input function has led to the development of approaches for its estimation. Theapplication of the methodology to the understanding of human metabolic disorders (obesity, impairedglucose tolerance, diabetes) highlights a tight reciprocal regulation between glucose and fatty acidmetabolism, suggesting that the liver is first engaged in counterbalancing the overflow of fatty acidsderiving from a dysfunctional adipose tissue, by the activation and/or exhaustion of oxidation and lipidaccumulation. These events may compromise hepatic insulin action and glucose metabolism. Oncechronic hyperglycaemia ensues, the capability of the liver to utilize fatty acids during fasting andglucose during insulin stimulation may become further defective. This chapter describes themethodological advances, and the clinical findings so far achieved by PET imaging in the field of livermetabolism in metabolic diseases. Hepatic glucose metabolism; Hepatic fatty acid m 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 >>

Quantifying The Contribution Of The Liver To Glucose Homeostasis: A Detailed Kinetic Model Of Human Hepatic Glucose Metabolism

Quantifying The Contribution Of The Liver To Glucose Homeostasis: A Detailed Kinetic Model Of Human Hepatic Glucose Metabolism

Abstract Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. Author Summary Glucose is an indispensable fuel for all cells and organs, but at the same time leads to problems at high concentrations. As a consequence, blood glucose is controlled in a narrow range to guarantee constant supply and on the other hand avoid damages associated with elevated glucose levels. The liver is the main organ controlling blood glucose by (i) releasing newly synthesized or s Continue reading >>

Glycogen

Glycogen

Schematic two-dimensional cross-sectional view of glycogen: A core protein of glycogenin is surrounded by branches of glucose units. The entire globular granule may contain around 30,000 glucose units.[1] A view of the atomic structure of a single branched strand of glucose units in a glycogen molecule. Glycogen (black granules) in spermatozoa of a flatworm; transmission electron microscopy, scale: 0.3 µm Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in humans,[2] animals,[3] fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body. Glycogen functions as one of two forms of long-term energy reserves, with the other form being triglyceride stores in adipose tissue (i.e., body fat). In humans, glycogen is made and stored primarily in the cells of the liver and skeletal muscle.[2][4] In the liver, glycogen can make up from 5–6% of the organ's fresh weight and the liver of an adult weighing 70 kg can store roughly 100–120 grams of glycogen.[2][5] In skeletal muscle, Glycogen is found in a low concentration (1–2% of the muscle mass) and the skeletal muscle of an adult weighing 70 kg can store roughly 400 grams of glycogen.[2] The amount of glycogen stored in the body—particularly within the muscles and liver—mostly depends on physical training, basal metabolic rate, and eating habits. Small amounts of glycogen are also found in other tissues and cells, including the kidneys, red blood cells,[6][7][8] white blood cells,[medical citation needed] and glial cells in the brain.[9] The uterus also stores glycogen during pregnancy to nourish the embryo.[10] Approximately 4 grams of glucose are present in the blood of humans at all times;[2] in fasted individuals, blood glucos 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 >>

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 >>

Metformin, The Liver, And Diabetes

Metformin, The Liver, And Diabetes

Most people think diabetes comes from pancreas damage, due to autoimmune problems or insulin resistance. But for many people diagnosed “Type 2,” the big problems are in the liver. What are these problems, and what can we do about them? First, some basic physiology you may already know. The liver is one of the most complicated organs in the body, and possibly the least understood. It plays a huge role in handling sugars and starches, making sure our bodies have enough fuel to function. When there’s a lot of sugar in the system, it stores some of the excess in a storage form of carbohydrate called glycogen. When blood sugar levels get low, as in times of hunger or at night, it converts some of the glycogen to glucose and makes it available for the body to use. Easy to say, but how does the liver know what to do and when to do it? Scientists have found a “molecular switch” called CRTC2 that controls this process. When the CRTC2 switch is on, the liver pours sugar into the system. When there’s enough sugar circulating, CRTC2 should be turned off. The turnoff signal is thought to be insulin. This may be an oversimplification, though. According to Salk Institute researchers quoted on RxPG news, “In many patients with type II diabetes, CRTC2 no longer responds to rising insulin levels, and as a result, the liver acts like a sugar factory on overtime, churning out glucose [day and night], even when blood sugar levels are high.” Because of this, the “average” person with Type 2 diabetes has three times the normal rate of glucose production by the liver, according to a Diabetes Care article. Diabetes Self-Management reader Jim Snell brought the whole “leaky liver” phenomenon to my attention. He has frequently posted here about his own struggles with soarin Continue reading >>

Blood Glucose And The Liver - Sciencedirect

Blood Glucose And The Liver - Sciencedirect

Volume 26, Issue 2 , February 1959, Pages 264-282 Get rights and content A graphical summary of those aspects of carbohydrate metabolism herein discussed, which contribute to the regulation of blood glucose under normal and pathological conditions, is presented in Figure 9. The rate-limiting steps are drawn in a schematic liver cell (A). The normal animal with a blood glucose concentration of 100 mg. per cent (B) slowly mobilizes glycogen to increase the concentration of glucose-6-phosphate (G6P) which in turn is depleted by the prevailing, relatively low level of blood glucose; thus glucose is produced by the liver. At 150 mg. per cent (C) there is no net flow of glucose into or out of the liver since both glucokinase (1) and glucose-6-phosphatase (2) are respectively metabolizing glucose and glucose-6-phosphate at the same rate. At 200 mg. per cent (D) glucokinase (1) phosphorylates more glucose molecules than are cleaved by glucose-6-phosphatase (2), the concentration of glucose-6-phosphate increases and glycogen is deposited. Thus glucose is cleared by the liver. In prolonged fasting states (E) glucokinase (1) falls by 50 per cent and glucose-6-phosphatase (2) increases. Thus glucose production is facilitated without a marked fall in blood glucose concentration. Intracellular glucose-6-phosphate concentration falls, effecting mobilization of glycogen. Fructose-1,6-diphosphatase activity (3) also increases and precursors are mobilized from the periphery under the influence of the adrenal cortex. In the diabetic liver (F) glucokinase is markedly decreased and glucose-6-phosphatase (2) is doubled. In spite of the alteration of both enzymes in favor of hepatic glucose production, the circulating hyperglycemia and the large inflow of precursors are able to keep the conc Continue reading >>

Glucose Homeostasis & The Liver

Glucose Homeostasis & The Liver

Blood glucose homeostasis is an important biologic process that involves a variety of mechanisms. The muscles, kidneys and liver all have important functions in glucose regulation. The liver is especially important for its ability to store glycogen and prevent low blood glucose. Video of the Day Maintaining blood glucose within the normal range is referred to as glucose homeostasis. Your brain and nervous system depend solely on glucose for fuel and require a steady supply of glucose at all times. It is critical that your blood glucose concentration remains within the range of 70 to 110 mg/dL to supply your brain and nervous system with adequate fuel. Low blood glucose can lead to symptoms such as dizziness or lack of concentration, whereas, over time, high blood glucose can damage blood vessels and nerves. Role of the liver Your liver plays a key role in blood glucose homeostasis. After a meal when blood glucose is high, the liver has the ability to remove glucose from the blood and store it as part of a molecule called glycogen. In between meals, as blood glucose begins to decline, the liver can make new glucose to release into the blood. Hormones, such as insulin and glucagon, regulate these homeostatic processes. In your body, glycogen serves as the glucose storage molecule. Glucose is stored as glycogen when blood glucose concentrations exceed energy demands. Glycogen is found primarily in your liver, but is found in smaller amounts in your muscles. Glycogen can be synthesized, or broken down, according to the needs of your body. Insulin directs the synthesis of glycogen, thus helping to lower elevated blood glucose. In response to the hormone glucagon, stored liver glycogen can be broken down and released into the blood to help raise blood glucose. In addition to Continue reading >>

Physiologic Effects Of Insulin

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 >>

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 >>

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 >>

Jci -hepatic Gi Signaling Regulates Whole-body Glucose Homeostasis

Jci -hepatic Gi Signaling Regulates Whole-body Glucose Homeostasis

In vivo metabolic studies in Hep-Di mice, which selectively express the Di designer receptor in hepatocytes. (AF) In vivo metabolic tests performed using Hep-Di mice and control littermates (CTR) treated with the AAV-TBG-EGFP control virus. (A and B) CNO challenge tests. Mice that had free access to food (fed) (A) or had been fasted overnight for approximately 12 hours (fasted) (B) were injected with CNO (10 mg/kg i.p.) or vehicle, followed by monitoring of blood glucose levels. (C) IGTTS (2 g glucose/kg i.p.). (D) PTT (2 g sodium pyruvate/kg i.p.). (E) ITTS (0.75 U insulin/kg i.p.). (F) Glucagon challenge test (16 g glucagon/kg i.p). (GJ) Effect of CNO on hepatic glucose fluxes in conscious Hep-Di mice in vivo. (G) Changes in arterial blood glucose levels and rates of (H) glucose appearance (endogenous glucose production [Endo-Ra]), (I) hepatic glycogenolysis, and (J) gluconeogenesis following CNO (10 mg/kg i.v.) treatment of Hep-Di and control mice. All experiments were carried out with chronically catheterized, conscious mice, as described in detail in Methods. After a 5-hour fast, mice were injected with CNO (10 mg/kg) at t0. Mice were maintained on regular chow. All studies were performed using 11- to 16-week-old male mice. Data represent the mean SEM (n = 68 mice/group). *P < 0.05, **P < 0.01, and ***P < 0.001 versus the corresponding control value. Significance was determined by (AF) 2-way ANOVA followed by Bonferronis post-hoc test and (GJ) 2-tailed Students t test. In an i.p. glucose tolerance test (IGTT), we found that CNO treatment (10 mg/kg i.p.) of control mice had no significant effect on blood glucose excursions as compared with saline-injected control or Hep-Di mice ( Figure 1C ). On the other hand, CNO administration led to a significant impairment in Continue reading >>

What Causes The Blood Glucose Level To Increase In Liver Damage?

What Causes The Blood Glucose Level To Increase In Liver Damage?

Chronic liver damage can result in the replacement of normal liver tissue with non-functioning scar tissue. Advanced liver damage is called cirrhosis, and glucose intolerance is a common feature of this condition. An article in the January 2009 issue of the “World Journal of Gastroenterology” reports that greater than 90 percent of people with liver cirrhosis are glucose intolerant, and nearly 30 percent will develop diabetes. Liver cirrhosis is irreversible and can be the result of alcoholic liver disease, hemochromatosis, non-alcoholic fatty liver disease or chronic hepatitis C infection. Video of the Day The liver is the primary disposal site of insulin; when the liver is damaged, less insulin is taken up and degraded, causing a condition of chronic hyperinsulinemia. A study in the July 1998 issue of “Hepatology” reports that hyperinsulinemia in patients with liver cirrhosis causes muscle insulin resistance. Another study in the March 1994 issue of “Hepatology” reports patients with cirrhosis exhibit metabolic abnormalities consistent with muscle tissue insulin resistance. This means that in people with impaired liver function, glucose is not as efficiently removed from the blood by muscle tissue, leading to a chronic elevation of blood glucose levels. Liver Insulin Resistance In people who have cirrhosis, insulin resistance eventually develops in the liver also. When the liver is less sensitive to insulin, it is no longer as effective in removing excess glucose from the blood or in converting glucose into the glucose-storage molecule, glycogen. As a result, blood glucose levels are higher, especially after a meal. Chronic insulin resistance and the resultant high circulating levels of glucose and fats eventually destroy the insulin-secreting cells, calle Continue reading >>

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