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How Does Insulin Play A Role In Metabolism?

Myhealthywaist.org - Glucose/insulin Homeostasis

Myhealthywaist.org - Glucose/insulin Homeostasis

Glucose is abundant in a wide range of foods. In the fasted state, the liver provides the bulk of glucose to the bloodstream through glycogenolysis and gluconeogenesis. Insulin optimizes glucose uptake by skeletal muscle, its major peripheral user. Insulin also reduces liver glucose production after a meal and reduces fatty acid release by adipose tissue. These three major functions are important for glucose homeostasis. Expansion of intra-abdominal (visceral) fat causes adipocyte hypertrophy. This process triggers macrophages that, together with the enlarged adipocytes, locally secrete insulin-resistance-promoting molecules. Hypertrophied insulin-resistant intra-abdominal adipocytes release more fatty acids and proinflammatory adipokines into the bloodstream. The portal circulation carries these to the liver where they promote steatosis, insulin resistance, and local inflammation. The systemic circulation carries fatty acids and proinflammatory molecules to skeletal muscle where they promote lipid accumulation, insulin resistance, and local inflammation. Insulin resistance also affects the function of other systems and organs, including endothelial cells and cells of the vascular wall. This further increases CVD risk. Insulin resistance is believed to play a role in the development of many metabolic abnormalities that define the metabolic syndrome. It is also believed to be a strong link between intra-abdominal obesity and increased risk of type 2 diabetes and CVD. Targeting the fundamental cause of obesity-related insulin resistance by reducing intra-abdominal fat mass remains an important therapeutic objective. One of the most common metabolic complications of intra-abdominal (visceral) obesity is insulin resistance, a condition in which insulin no longer functions Continue reading >>

Insulin

Insulin

This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin (medication). Not to be confused with Inulin. Insulin (from Latin insula, island) is a peptide hormone produced by beta cells of the pancreatic islets, and it is considered to be the main anabolic hormone of the body.[5] It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells.[6] In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.[6] Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood.[7] Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.[8] Their neighboring alpha cells, by taking their cues from the beta cells,[8] secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high.[6][8] Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.[6][8] The secretion of insulin and glucagon into the Continue reading >>

Assessment Of The Role Of Metabolic Determinants On The Relationship Between Insulin Sensitivity And Secretion

Assessment Of The Role Of Metabolic Determinants On The Relationship Between Insulin Sensitivity And Secretion

Assessment of the Role of Metabolic Determinants on the Relationship between Insulin Sensitivity and Secretion Affiliations Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile, UDA-Ciencias de la Salud, Carrera de Nutricin y Diettica, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Departamento de Nutricin, Diabetes y Metabolismo, Escuela de Medicina, Pontificia Universidad Catlica de Chile, Santiago, Chile Affiliation Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, Padova, Italy Continue reading >>

Insulin Resistance And Lipid Disorders

Insulin Resistance And Lipid Disorders

Roberto Miccoli; Cristina Bianchi; Giuseppe Penno; Stefano Del Prato Dysregulation of Lipid Metabolism and Insulin Resistance Whilst current definitions may still define insulin resistance in terms of insulin effects on glucose metabolism, the last decade has seen a shift from the traditional 'glucocentric' view of the syndrome associated with insulin resistance to an increasingly acknowledged 'lipocentric' viewpoint. The notion that lipids may act as signaling factors that regulate metabolic functions in target tissues was first suggested more than 40 years ago, when Randle et al. hypothesized that obesity-associated insulin resistance could be explained by substrate competition between increased circulating NEFA and glucose for oxidative metabolism in insulin-responsive cells. The importance of NEFA and lipid metabolism was also outlined by McGarry, who suggested that insulin resistance and concomitant hyperglycemia could be viewed in the context of underlying abnormalities of lipid metabolism.[ 67 ] More recently, glucose uptake, rather than intracellular glucose metabolism, has been implicated as a rate-limiting step for NEFA-induced insulin resistance.[ 68 ] In this model, NEFA and some of their metabolites, including acyl-CoA, ceramides and diacyglycerol, have been demonstrated to serve as signaling molecules that activate protein kinases such as PKC, JNK and IKK. These kinases can impair insulin signaling by increasing inhibitory serine phosphorylation of insulin receptor substrates (IRS), the key mediators of insulin signaling, and activating an inflammatory response.[ 68 ] In such a lipocentric framework, the term lipotoxicity was introduced by Unger to describe the deleterious effect of TG accumulation in pancreatic -cells, resulting in impaired glucose-stimu Continue reading >>

The Role Of Glucose In Your Metabolism

The Role Of Glucose In Your Metabolism

Insulin, a hormone produced by the beta cells of your pancreas, regulates carbohydrate and fat metabolism. Insulin is one of four main need-to-know hormones that plays a major role in your metabolism. It’s released when it senses carbohydrate or protein in your blood as they’re being digested. It causes your cells to take up glucose to be used for energy or to store either in the liver or muscle as glycogen or in your fat cells as triglycerides. When present, insulin stops your body from breaking down stored fat to use for energy. Insulin stimulates protein synthesis and encourages amino acid uptake by your muscles. When your metabolism is working at its peak, your body has feedback mechanisms to regulate the amount of insulin your body makes so there’s neither too much nor too little. That way, you’re using glucose appropriately for energy and not storing too much fat. If you have diabetes, your body either doesn’t make enough (or any!) insulin or your body doesn’t respond well to it, which is known as insulin resistance. But if your cells aren’t as receptive to insulin, there are ways to help reverse that. By seeking out medical care, making changes to your diet and activity levels, and achieving a healthy weight, you can regulate your blood glucose. Continue reading >>

Glucose Metabolism

Glucose Metabolism

Energy is required for the normal functioning of the organs in the body. Many tissues can also use fat or protein as an energy source but others, such as the brain and red blood cells, can only use glucose. Glucose is stored in the body as glycogen. The liver is an important storage site for glycogen. Glycogen is mobilized and converted to glucose by gluconeogenesis when the blood glucose concentration is low. Glucose may also be produced from non-carbohydrate precursors, such as pyruvate, amino acids and glycerol, by gluconeogenesis. It is gluconeogenesis that maintains blood glucose concentrations, for example during starvation and intense exercise. The endocrine pancreas The pancreas has both endocrine and exocrine functions. The endocrine tissue is grouped together in the islets of Langerhans and consists of four different cell types each with its own function. Alpha cells produce glucagon. Beta cells produce proinsulin. Proinsulin is the inactive form of insulin that is converted to insulin in the circulation. Delta cells produce somatostatin. F or PP cells produce pancreatic polypeptide. Regulation of insulin secretion Insulin secretion is increased by elevated blood glucose concentrations, gastrointestinal hormones and Beta adrenergic stimulation. Insulin secretion is inhibited by catecholamines and somatostatin. The role of insulin and glucagon in glucose metabolism Insulin and glucagon work synergistically to keep blood glucose concentrations normal. Insulin: An elevated blood glucose concentration results in the secretion of insulin: glucose is transported into body cells. The uptake of glucose by liver, kidney and brain cells is by diffusion and does not require insulin. Click on the thumbnail for details of the effect of insulin: Glucagon: The effects of glu Continue reading >>

Actions Of Insulin On The Mammalian Heart: Metabolism, Pathology And Biochemical Mechanisms

Actions Of Insulin On The Mammalian Heart: Metabolism, Pathology And Biochemical Mechanisms

Actions of insulin on the mammalian heart: metabolism, pathology and biochemical mechanisms aDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Copp Building, Medical Block A, 2146 Health Sciences Mall, Vancouver, B.C., Canada V6T 1Z3 Corresponding author. Tel.: +1 (604) 822-3810; Fax: +1 (604) 822-5227; e-mail: [email protected] Search for other works by this author on: aDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Copp Building, Medical Block A, 2146 Health Sciences Mall, Vancouver, B.C., Canada V6T 1Z3 Search for other works by this author on: bDepartment of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, B.C, Canada Search for other works by this author on: Cardiovascular Research, Volume 34, Issue 1, 1 April 1997, Pages 324, Roger W. Brownsey, Adrienne N. Boone, Michael F. Allard; Actions of insulin on the mammalian heart: metabolism, pathology and biochemical mechanisms, Cardiovascular Research, Volume 34, Issue 1, 1 April 1997, Pages 324, Skeletal muscle, adipose tissue and liver are the quantitatively major targets for insulin action in vivo and regulation of critical steps in intermediary metabolism within these tissues account for many of the impacts of insulin on metabolic homeostasis. Many other tissues including the heart express insulin receptors and their functions may be importantly regulated by insulin. In this review we summarize the evidence that the heart is an important target of insulin action and that abrogation of these actions is important in disease states. Current understanding of the molecular basis of insulin actions on its target cells is drawn from a large literature emanating from studies of the major target tissues and also fr Continue reading >>

What Is Insulin?

What Is Insulin?

Insulin is a hormone; a chemical messenger produced in one part of the body to have an action on another. It is a protein responsible for regulating blood glucose levels as part of metabolism.1 The body manufactures insulin in the pancreas, and the hormone is secreted by its beta cells, primarily in response to glucose.1 The beta cells of the pancreas are perfectly designed "fuel sensors" stimulated by glucose.2 As glucose levels rise in the plasma of the blood, uptake and metabolism by the pancreas beta cells are enhanced, leading to insulin secretion.1 Insulin has two modes of action on the body - an excitatory one and an inhibitory one:3 Insulin stimulates glucose uptake and lipid synthesis It inhibits the breakdown of lipids, proteins and glycogen, and inhibits the glucose pathway (gluconeogenesis) and production of ketone bodies (ketogenesis). What is the pancreas? The pancreas is the organ responsible for controlling sugar levels. It is part of the digestive system and located in the abdomen, behind the stomach and next to the duodenum - the first part of the small intestine.4 The pancreas has two main functional components:4,5 Exocrine cells - cells that release digestive enzymes into the gut via the pancreatic duct The endocrine pancreas - islands of cells known as the islets of Langerhans within the "sea" of exocrine tissue; islets release hormones such as insulin and glucagon into the blood to control blood sugar levels. Islets are highly vascularized (supplied by blood vessels) and specialized to monitor nutrients in the blood.2 The alpha cells of the islets secrete glucagon while the beta cells - the most abundant of the islet cells - release insulin.5 The release of insulin in response to elevated glucose has two phases - a first around 5-10 minutes after g Continue reading >>

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 >>

Glucose Metabolism And Regulation: Beyond Insulin And Glucagon

Glucose Metabolism And Regulation: Beyond Insulin And Glucagon

Insulin and glucagon are potent regulators of glucose metabolism. For decades, we have viewed diabetes from a bi-hormonal perspective of glucose regulation. This perspective is incomplete and inadequate in explaining some of the difficulties that patients and practitioners face when attempting to tightly control blood glucose concentrations. Intensively managing diabetes with insulin is fraught with frustration and risk. Despite our best efforts, glucose fluctuations are unpredictable, and hypoglycemia and weight gain are common. These challenges may be a result of deficiencies or abnormalities in other glucoregulatory hormones. New understanding of the roles of other pancreatic and incretin hormones has led to a multi-hormonal view of glucose homeostasis. HISTORICAL PERSPECTIVE Our understanding of diabetes as a metabolic disease has evolved significantly since the discovery of insulin in the 1920s. Insulin was identified as a potent hormonal regulator of both glucose appearance and disappearance in the circulation. Subsequently, diabetes was viewed as a mono-hormonal disorder characterized by absolute or relative insulin deficiency. Since its discovery, insulin has been the only available pharmacological treatment for patients with type 1 diabetes and a mainstay of therapy for patients with insulin-deficient type 2 diabetes.1–7 The recent discovery of additional hormones with glucoregulatory actions has expanded our understanding of how a variety of different hormones contribute to glucose homeostasis. In the 1950s, glucagon was characterized as a major stimulus of hepatic glucose production. This discovery led to a better understanding of the interplay between insulin and glucagon, thus leading to a bi-hormonal definition of diabetes. Subsequently, the discovery of Continue reading >>

[regulation Of Carbohydrate Metabolism By Insulin: Role Of Transcription Factor Srebp-1c In The Hepatic Transcriptional Effects Of The Hormone].

[regulation Of Carbohydrate Metabolism By Insulin: Role Of Transcription Factor Srebp-1c In The Hepatic Transcriptional Effects Of The Hormone].

Abstract A number of tissues such as the brain must be continuously provided with glucose to meet their energy demand. In contrast, carbohydrate absorption during meals is a discontinuous process. Thus, we must store glucose when its is provided, release it or spare it when it is less abundant. Insulin, secreted by the pancreatic beta-cell is a key hormone in the adaptations of metabolic pathways linked to glucose homeostasis. It inhibits hepatic glucose production, promotes glucose storage in the liver and glucose uptake and storage in muscles and adipose tissues. This is achieved through the modifications of the activity of existing proteins (enzymes, transporters) but also through the regulation of gene expression. In the liver, when the diet is rich in carbohydrates, insulin is secreted and stimulates the expression of genes involved in glucose utilization (glucokinase, L-pyruvate kinase, lipogenic enzymes) and inhibits genes involved in glucose production (phosphenolpyruvate carboxykinase). The mechanisms by which insulin controls the expression of these genes were poorly understood. Recently, the transcription factor Sterol Regulatory Element Binding Protein-1c (SREBP-1c) has been proposed as a key mediator of insulin transcriptional effects. Insulin increases the synthesis and nuclear abundance of this factor which when overexpressed in the liver mimics the effects of insulin on insulin-sensitive genes. This suggests that SREBP-1c could be involved in pathologies such as type 2 diabetes, obesity and more generally in insulin resistance syndromes. Continue reading >>

The Science Of Insulin

The Science Of Insulin

Insulin is perhaps the most well known of all hormones and in the halls of health, fitness, and fat loss. It is mostly maligned and drastically misunderstood. As with many things in health and fitness there is more to the simple story told about insulin. Insulin basics Insulin functions very much like your hands when you are eating. Just as it would be extremely difficult to eat without hands, insulin feeds the tissue of the body in the same way. Insulin is required to facilitate nutrient uptake in the cells. Without insulin, your cells would literally starve and die. Insulin is made in the beta cells of the pancreas and is released into the blood stream in response to food. It assures these nutrients get into the cell. Insulin’s primary job is to make sure the cells have enough glucose, and therefore it has a strong impact on blood sugar levels. In fact, glucose is the primary stimulator of insulin release. In response to food and/or stress, blood glucose levels will rise. Insulin is used to lower blood sugar and balance things back out. Insulin Resistance Insulin works by increasing the amount of glucose receptors on the membranes of cells. So, when insulin interacts with cellular physiology it results in an increased ability for the cell to take in glucose. When insulin is repeatedly secreted in large quantities, over time the cells become less sensitive to its message. This is analogous to walking into a room with a strong smell. When you first enter, you are acutely aware of the odor and may cover your nose in response. After several minutes however, the smell becomes diminished and you no longer smell it. This is what happens to the cells when they become insulin resistant. They no longer respond to insulin the same way. This has consequences for cellular energy Continue reading >>

The Role Of Insulin In The Body

The Role Of Insulin In The Body

Tweet Insulin is a hormone which plays a key role in the regulation of blood glucose levels. A lack of insulin, or an inability to adequately respond to insulin, can each lead to the development of the symptoms of diabetes. In addition to its role in controlling blood sugar levels, insulin is also involved in the storage of fat. Insulin is a hormone which plays a number of roles in the body’s metabolism. Insulin regulates how the body uses and stores glucose and fat. Many of the body’s cells rely on insulin to take glucose from the blood for energy. Insulin and blood glucose levels Insulin helps control blood glucose levels by signaling the liver and muscle and fat cells to take in glucose from the blood. Insulin therefore helps cells to take in glucose to be used for energy. If the body has sufficient energy, insulin signals the liver to take up glucose and store it as glycogen. The liver can store up to around 5% of its mass as glycogen. Some cells in the body can take glucose from the blood without insulin, but most cells do require insulin to be present. Insulin and type 1 diabetes In type 1 diabetes, the body produces insufficient insulin to regulate blood glucose levels. Without the presence of insulin, many of the body’s cells cannot take glucose from the blood and therefore the body uses other sources of energy. Ketones are produced by the liver as an alternative source of energy, however, high levels of the ketones can lead to a dangerous condition called ketoacidosis. People with type 1 diabetes will need to inject insulin to compensate for their body’s lack of insulin. Insulin and type 2 diabetes Type 2 diabetes is characterised by the body not responding effectively to insulin. This is termed insulin resistance. As a result the body is less able to t Continue reading >>

Insulin's Role In The Human Body

Insulin's Role In The Human Body

Insulin is a hormone produced by the pancreas that has a number of important functions in the human body, particularly in the control of blood glucose levels and preventing hyperglycemia. It also has an effect on several other areas of the body, including the synthesis of lipids and regulation of enzymatic activity. Insulin and Metabolic Processes The most important role of insulin in the human body is its interaction with glucose to allow the cells of the body to use glucose as energy. The pancreas usually produces more insulin in response to a spike in blood sugar level, for example after eating a meal high in energy. This is because the insulin acts as a “key” to open up the cells in the body and allows the glucose to be used as an energy source. Additionally, when there is excess glucose in the bloodstream, known as hyperglycemia, insulin encourages the storage of glucose as glycogen in the liver, muscle and fat cells. These stores can then be used at a later date when energy requirements are higher. As a result of this, there is less insulin in the bloodstream, and normal blood glucose levels are restored. Insulin stimulates the synthesis of glycogen in the liver, but when the liver is saturated with glycogen, an alternative pathway takes over. This involves the uptake of additional glucose into adipose tissue, leading to the synthesis of lipoproteins. Results Without Insulin In the absence of insulin, the body is not able to utilize the glucose as energy in the cells. As a result, the glucose remains in the bloodstream and can lead to high blood sugar, known as hyperglycemia. Chronic hyperglycemia is characteristic of diabetes mellitus and, if untreated, is associated with severe complications, such as damage to the nervous system, eyes, kidneys and extremitie Continue reading >>

Glucose Metabolism

Glucose Metabolism

Despite periods of feeding and fasting, in normal individuals plasma glucose remains in a narrow range between 4 and 7 mM reflecting the balance between: (i) the release of glucose into the circulation by either absorption from the intestine or the breakdown of stored glycogen in the liver and (ii) the uptake and metabolism of blood glucose by peripheral tissues[1]. These processes are controlled by a set of metabolic hormones. For decades diabetes had been viewed from a bi-hormonal perspective of glucose regulation involving insulin (discovered in the 1920s; released by pancreatic β-cells ) and glucagon (discovered in the 1950s; released by the pancreatic α-cells)[2]. In the mid-1970s several gut hormones, the incretins, were identified. One of these, glucagon-like peptide-1 (GLP-1), was recognized as another important contributor to the maintenance of glucose homeostasis. Subsequently the discovery in 1987, of a second pancreatic β-cell hormone, amylin, whose role complemented that of insulin, led to the view of glucose homeostasis involving multiple hormones[2]. Amylin, like insulin is found to be deficient in people with diabetes. Hormones produced by adipose tissue also play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. These include leptin, adiponectin, acylation stimulating protein and resistin . Hormones involved Pancreatic β-cell hormones Insulin is a key anabolic hormone that is secreted from pancreatic β-cells in response to increased blood glucose and amino acids following ingestion of a meal. Insulin, through its action on the insulin receptor decreases blood sugar levels by: (i) increasing glucose uptake in muscle and fat through triggering the translocation of the intracellular glucose Continue reading >>

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