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Insulin Resistance Pathophysiology

Insulin Resistance Pathophysiology

Insulin Resistance Pathophysiology

Glucose is one of the body's most important sources of energy. Glucose is absorbed from the blood into cells where it provides energy for a range of cellular functions. This cellular uptake of glucose is facilitated by the hormone insulin, which is secreted by the beta cells of the pancreas. Insulin also helps convert excess glucose into glycogen for storage in the liver. Consuming one hundred percent fruit juice does not alter blood sugar levels, study suggests In people with insulin resistance, the muscles, fat and liver cells fail to respond to insulin in this way and glucose remains in the blood rather than being taken up, even when insulin levels are raised. Instead, the triglycerides in fat or adipose cells are broken down to provide free fatty acids as the energy source. Failure of liver cells to respond to insulin by converting glucose to glycogen, means glycogen stores are also decreased. As the glucose remains in the blood rather than being taken up and used, hyperglycemia or a raised blood glucose level results. This hyperglycemia triggers the beta cells to produce even more insulin, raising the level of insulin further still. This insulin resistance and hyperglycemia can lead to type 2 diabetes and metabolic syndrome. Metabolic syndrome is characterized by an excess distribution of abdominal fat, high blood pressure, raised levels of blood cholesterol and triglycerides and decreased levels of good cholesterol or high density lipoprotein (HDL) cholesterol. Together, these symptoms increase the risk of cardiovascular disease and stroke. A variety of genetic and environmental factors are thought to raise the risk of insulin resistance but being overweight and physically inactive are major causative contributors. Continue reading >>

Insulin Resistance: Pathophysiology And Natural Therapeutics

Insulin Resistance: Pathophysiology And Natural Therapeutics

36 Hours CE Credit with Certificate The CD-Set, Notes, and Supplemental Readings and Texts may be purchased separately without enrollment in the course and with no additional tuition fee. Overview Learn the basic pathophysiology of insulin resistance and it role in modern chronic disease Learn the anthropology of insulin resistance, and see what normal health and blood parameters are in our close hunter gatherer relatives. Learn how to assess insulin resistance through blood work Learn how to assess a patient for insulin resistance using nothing more than an interview and a tape measure. Learn the role of basic nutrients essential to normal insulin function Learn the role of trained muscle status on overall insulin and glucose effects in the body Learn the role of glycemic index, glycemic load, and total carbohydrate percentage in insulin resistance Learn the basic science of a ketogenic diet Learn how to prepare a patient for ketosis in stages to reduce the unpleasantness of the induction phase Learn how to coach a patient for a complete ketogenic diet. Learn herbs which may benefit insulin and insulin resistance, as opposed to simply lowering blood sugar Learn how to use a basic insulin resistance protocol in the treatment of prediabetes, diabetes, vascular diseases, cancers, neurological diseases, and reproductive dysfunction, including PCOS Insulin resistance is the root pathology not only of Type II diabetes, but also contributes to heart disease, stroke, obesity, hypertension, several common cancers, and other conditions ranging from polycystic ovarian disease to acne to brittle bones and depression. It is a pathology fundamental to the “diseases of civilization.” Although cell level pathology is complex, the roots of this condition are based in malnutrition i Continue reading >>

Insulin Resistance And Type 2 Diabetes

Insulin Resistance And Type 2 Diabetes

For well over half a century, the link between insulin resistance and type 2 diabetes has been recognized. Insulin resistance is important. Not only is it the most powerful predictor of future development of type 2 diabetes, it is also a therapeutic target once hyperglycemia is present. In this issue of Diabetes, Morino et al. (1) report a series of studies that provide evidence of a genetic mechanism linking expression of lipoprotein lipase (LPL) to peroxisome proliferator–activated receptor (PPAR)-δ expression and mitochondrial function. This is likely to contribute to the muscle insulin resistance that predisposes to type 2 diabetes. Observation of abnormal mitochondrial function in vitro in type 2 diabetes (2) was soon followed by in vivo demonstration of this abnormality in insulin-resistant, first-degree relatives of people with type 2 diabetes (3). Further reports of a modest defect in muscle mitochondrial function in type 2 diabetes were published shortly thereafter (4,5). These studies raised the question of whether type 2 diabetes could be a primary disorder of the mitochondria. However, the study of first-degree relatives tended to be misinterpreted as having shown a major defect in mitochondrial function in type 2 diabetes, although it had studied nondiabetic groups from the opposite ends of the insulin resistance–sensitivity spectrum. Indeed, other studies showed no defect in mitochondrial function in type 2 diabetes (6,7), which led to further confusion. Mitochondrial function was then shown to be acutely modifiable by changing fatty acid availability (8) and that it was affected by ambient blood glucose concentration (9). When ambient blood glucose levels were near normal in diabetes, no defect in mitochondrial function was apparent. But if mitochond Continue reading >>

Pathophysiology And Pharmacological Treatment Of Insulin Resistance

Pathophysiology And Pharmacological Treatment Of Insulin Resistance

Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic -cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., -glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease. DIABETES mellitus type 2 represents the final stage of a chronic and progressive syndrome representing a heterogeneous disorder caused by various combinations of insulin resistance and decreased pancreatic -cell function caused by both genetic and acquired abnormalities ( 1 7 ). Currently, type 2 diabetes mellitus is diagnosed when the underlying metabolic abnormalities consisting of insulin resistance and decreased -cell function cause elevation of plasma glucose above 126 mg/dl (7 mmol/liter) in the fasting state and/or above 200 mg/dl (11.1 mmol/liter) 120 min after a 75-g glucose load ( 8 ). However, the fact that many newly diagnosed type 2 diabetic subjects already suffer from so called late complications of diabetes at the time of diagnosis ( 9 ) indicates that the diagnosis may have bee Continue reading >>

Jci -series Introduction: The Molecular And Physiological Basis Of Insulin Resistance: Emerging Implications For Metabolic And Cardiovascular Diseases

Jci -series Introduction: The Molecular And Physiological Basis Of Insulin Resistance: Emerging Implications For Metabolic And Cardiovascular Diseases

Perspective Free access | 10.1172/JCI10533 Series Introduction: The molecular and physiological basis of insulin resistance: emerging implications for metabolic and cardiovascular diseases Department of Physiology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. Department of Cell Biology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Co., Ann Arbor, Michigan, USA Address correspondence to: Alan R. Saltiel, Department of Cell Biology, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, Michigan 48105-2430, USA. Phone: (734) 622-7316; Fax: (734) 622-5668; E-mail: [email protected] . Find articles by Saltiel, A. in: JCI | PubMed | Google Scholar First published January 15, 2000- More info Published in Volume 106, Issue 2 (July 15, 2000) J Clin Invest.2000;106(2):163164.doi:10.1172/JCI10533. Copyright 2000, The American Society for Clinical Investigation. Following the discovery of insulin by Banting and Best in 1922, it was widely assumed that human diabetes was due exclusively to a deficiency in the secretion of the hormone. However, 10 years later Himsworth ( 1 ) noted variations in the responses of diabetic patients to insulin and proposed the notion that insulin insensitivity, not insulin deficiency, was the defining biochemical defect in many diabetics. This idea was not considered seriously until the development of the radioimmunoassay by Berson and Yalow ( 2 ), who showed that subjects with adult onset (type 2) diabetes tended to exhibit higher than average levels of circulating insulin. Later studies from Roth ( 3 ), Reaven ( 4 , 5 ), Olefsky ( 6 ), and others corroborated these findings and provided a mechanistic basis for the idea that insulin resistance plays a major role in diabetes. We now know that the p Continue reading >>

Pathophysiology Of Insulin Resistance - Sciencedirect

Pathophysiology Of Insulin Resistance - Sciencedirect

Volume 20, Issue 4 , December 2006, Pages 665-679 Author links open overlay panel GiorgioSestiMD(Professor of Internal Medicine) Get rights and content Insulin resistance is a feature of a number of clinical disorders, including type 2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertension clustering in the so-called metabolic syndrome. Insulin resistance in skeletal muscle manifests itself primarily as a reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport. Ectopic lipid accumulation plays an important role in inducing insulin resistance. Multiple defects in insulin signalling are responsible for impaired glucose metabolism in target tissues of subjects with features of insulin resistance. Inflammatory molecules and lipid metabolites inhibit insulin signalling by stimulating a number of different serine kinases which are responsible for serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1). Continue reading >>

Pathophysiology And Pathogenesis Of Gdm

Pathophysiology And Pathogenesis Of Gdm

Last Updated on Thu, 08 Mar 2018 | Insulin Resistance Normal pregnancy and GDM are states of profound insulin resistance and the mediating factors are similar, if not identical. However, women who develop GDM tend also to be insulin-resistant when not pregnant and become even more insulin-resistant during pregnancy [18]. GDM develops when p cells are unable to compensate the increasing insulin resistance with sufficiently greater insulin secretion to maintain normal fasting and/or postprandial glucose concentrations [18, 19]. For many years, clinical and research evidence has indicated a role for the placenta in the development of insulin resistance and the list of putative mediators of this effect is long (table 2). The placenta is also an endocrine organ and numerous studies have demonstrated potential mechanisms for hormones of placental origin to contribute to insulin resistance. Furthermore, insulin sensitivity is restored quickly after the placenta is expelled. In the last several years, it has been demonstrated that the placenta synthesizes and potentially secretes an array of mediators and cytokines (e.g. leptin , C-reac-tive protein, tumor necrosis factor (TNF)-a, interleukins 6 and 8) that may influence maternal metabolism and insulin sensitivity directly or indirectly [20]. Radaelli et al. [21] compared patterns of gene expression in placentas from pregnancies with normal glucose metabolism or GDM. They found major differences in the expression profiles with increases in markers and mediators of inflammation (interleukins, leptin and TNF-a receptors and downstream adaptors) in GDM. Whether these alterations of gene expression Table 2. Factors of placental origin that putatively contribute to insulin resistance Large placenta size Human placental lactogen (pl Continue reading >>

A Complex Relationship Between Immunity And Metabolism In Drosophila Diet-induced Insulin Resistance

A Complex Relationship Between Immunity And Metabolism In Drosophila Diet-induced Insulin Resistance

A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance aBinghamton University, Department of Biological Sciences, Binghamton, New York, USA bWashington University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, Missouri, USA cBioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA Both systemic insulin resistance and tissue-specific insulin resistance have been described in Drosophila and are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body studying loss and gain of function. When expression of the sole Drosophila insulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, transcriptome sequencing (RNA-seq) studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathway Continue reading >>

Acanthosis Nigricans Associated With Insulin Resistance : Pathophysiology And Management.

Acanthosis Nigricans Associated With Insulin Resistance : Pathophysiology And Management.

Acanthosis nigricans associated with insulin resistance : pathophysiology and management. American Journal of Clinical Dermatology [01 Jan 2004, 5(3):199-203] The association of acanthosis nigricans, skin tags, diabetes mellitus due to insulin resistance, and obesity in adolescents and young adults represents a well defined syndrome. Hyperandrogenism may also be present. The endocrine origin of this condition is beyond doubt. Insulin and insulin-like growth factor-1, and their receptors on keratinocytes are obviously involved in the complex regulations leading to the peculiar epidermal hyperplasia. This condition is unrelated to other types of acanthosis nigricans, including the congenital and the paraneoplastic types. Control of obesity contributes largely to reverse the whole process, essentially by reducing both insulin resistance and compensatory hyperinsulinemia. Several drugs including metformin, octreotide, retinoids and topical colecalciferol (vitamin D(3)) analogs are also beneficial in clearing acanthosis nigricans. Continue reading >>

Pathophysiology - Type Ii Diabetes

Pathophysiology - Type Ii Diabetes

- Diabetes Mellitus is a group of disorders that's caused by improper function of insulin, which is a hormone produced by the pancreas. And insulin is responsible for helping regulate blood sugar, or glucose levels, in the blood. Now since it's a group of diseases, there are actually multiple different underlying causes of diabetes mellitus. And one of these causes is known as Type 2 Diabetes. Now, before we dive into the actual cause of Type 2 Diabetes, let's first get a better understanding of how exactly insulin works. And there are two major steps. So, imagine that you just ate a big meal. Maybe like a bowl of pasta or something. And your body is currently absorbing all of those nutrients from your digestive system into your bloodstream. Now one of these nutrients is glucose, and as your body absorbs it, that glucose starts building up in the blood stream. And in this feeding or absorptive state, your body wants to store this glucose in places like the liver and muscle cells so that it can be used for energy later when the body needs it. But unfortunately, glucose on its own can't get into these cells. In a sense, these cells are locked. But fortunately, the pancreas is able to help with this problem. So there are a couple types of cells in the pancreas that sense blood sugar levels. And these cells are located in the islets of Langerhans. And these green cells here in the islets of Langerhans are meant to represent the Beta cells. And when the blood glucose increases, the Beta cells of the pancreas sense this change, and they secrete a hormone known as insulin into the blood. And what insulin does is it acts like a key that can unlock these cells so that the glucose can be stored in both the liver and the muscle cells. So you can see that there are two steps in ord Continue reading >>

68: Insulin Action, Insulin Resistance, And Type 2 Diabetes Mellitus

68: Insulin Action, Insulin Resistance, And Type 2 Diabetes Mellitus

Abstract Abstract Diabetes mellitus is a syndrome characterized by elevated levels of glucose in the plasma. The American Diabetes Association has recently proposed revised criteria for the diagnosis of diabetes: (a) a fasting plasma glucose level >126 mg/dl, or (b) a plasma glucose level >200 mg/dl at 2 h after the ingestion of oral glucose (75 g), or (c) random plasma glucose >200 mg/dl. Diabetes is a heterogeneous clinical syndrome with multiple etiologies. Type 1 diabetes is caused by destruction of pancreatic beta cells, most often by autoimmune mechanisms. Type 2 diabetes (the most common form of diabetes, accounting for >90 percent of patients) is caused by a combination of two physiological defects: resistance to the action of insulin combined with a deficiency in insulin secretion. Although the molecular basis of the common form of type 2 diabetes has not been elucidated, it is thought to result from genetic defects that cause both insulin resistance and insulin deficiency. Type 2 diabetes generally has onset after the age of 40. Unlike type 1 diabetes, type 2 diabetes is usually associated with relatively mild hyperglycemia, and ketoacidosis seldom develops. Gestational diabetes mellitus is a form of diabetes that has its initial onset during pregnancy, and resolves after the end of the pregnancy. Insulin exerts multiple effects upon target cells—especially skeletal muscle, liver, and adipose tissue. In general, insulin promotes storage of fuels (e.g., glycogen and triglyceride), and inhibits the breakdown of stored fuel. To accomplish these general physiological functions, insulin exerts multiple specific actions upon target cells. For example, insulin promotes recruitment of glucose transporters from intracellular vesicles to the plasma membrane, thereby s Continue reading >>

Pathophysiology Of Insulin Resistance

Pathophysiology Of Insulin Resistance

Insulin is a hormone promote anabolism that balances individual caloric needs and intake with disbursement. Basically it raise store of excess carbohydrate and protein breakdown in forms of lipids and inhibits the opposite. Insulin resistance is impairment in the function of insulin targets cells such as liver cell, adipocytes and musculoskeletal cells to react to the insulin action.1 It is collection of many clinical metabolic disorders such as type 2 diabetes mellitus, hypertension, obesity and dyslipidaemia clustering known as metabolic syndrome.2 Global incidence of type 2 diabetes mellitus roughly will be around 250 million individual by the year 2020.3In spite that the basic causing factors is unknown, it is obvious that insulin resistance act as major part in its development. Judge by existence of insulin resistance before occurrence of the disease 10 -20 years back. 45 Insulin resistance pathologically grow through many interactions of genotype lifestyle change mainly sedentary life and over eating.67 Physiologically, many circulating factors regulate insulin sensitivity in target tissue such as adipokines, plasma lipid and circulating hormones plus their signalling pathways.89 There is neuroendocrine axis involve adipose tissue with brain and gut which regulate insulin metabolism by adjusting insulin sensitivity in target tissues.10Adipokines are hormone secreted by adipocytes store where some stimulate and other inhibit insulin sensitivity. In peripheral tissue insulin action is stimulated by Leptin and adiponectin. on the other hand, TNF, resistin, IL-6, and retinol binding protein 4 supress insulin sensitivity.11 Although metabolism and nutrition are regulated by adipocyte derived factors pattern of life, overweight and genetic can disturb this balance.12 I Continue reading >>

Pathophysiology Of Insulin Resistance.

Pathophysiology Of Insulin Resistance.

1. Best Pract Res Clin Endocrinol Metab. 2006 Dec;20(4):665-79. (1)Universit Magna Graecia di Catanzaro, Campus Universitario Germaneto di Catanzaro, 88100 Catanzaro, Italy. [email protected] Insulin resistance is a feature of a number of clinical disorders, including type2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertensionclustering in the so-called metabolic syndrome. Insulin resistance in skeletalmuscle manifests itself primarily as a reduction in insulin-stimulated glycogensynthesis due to reduced glucose transport. Ectopic lipid accumulation plays animportant role in inducing insulin resistance. Multiple defects in insulinsignalling are responsible for impaired glucose metabolism in target tissues ofsubjects with features of insulin resistance. Inflammatory molecules and lipidmetabolites inhibit insulin signalling by stimulating a number of differentserine kinases which are responsible for serine phosphorylation of InsulinReceptor Substrate-1 (IRS-1). Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatase, Non-Receptor Type 1 Continue reading >>

Insulin Resistance: Practice Essentials, Pathophysiology, Etiology

Insulin Resistance: Practice Essentials, Pathophysiology, Etiology

Insulin resistance is a state in which a given concentration of insulin produces a less-than-expected biological effect. Insulin resistance has also been arbitrarily defined as the requirement of 200 or more units of insulin per day to attain glycemic control and to prevent ketosis. The syndromes of insulin resistance actually make up a broad clinical spectrum, which includes obesity, glucose intolerance, diabetes, and the metabolic syndrome, as well as an extreme insulin-resistant state. Many of these disorders are associated with various endocrine, metabolic, and genetic conditions. These syndromes may also be associated with immunological diseases and may exhibit distinct phenotypic characteristics. [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] The metabolic syndrome a state of insulin-resistance that is also known as either syndrome X or the dysmetabolic syndromehas drawn the greatest attention because of its public health importance. In addition to hypertension, findings can include central obesity, peripheral arterial disease, type A syndrome, type B syndrome, ancanthosis nigricans, polycystic ovary syndrome, and other insulin-resistant states. In clinical practice, no single laboratory test is used to diagnose insulin resistance syndrome. Diagnosis is based on clinical findings corroborated with laboratory tests. Individual patients are screened based on the presence of comorbid conditions. Lab tests include the plasma glucose level, the fasting insulin level, and a lipid profile, among others. Treatment involves pharmacologic therapy to reduce insulin resistance, along with surgical management of underlying causes if appropriate. Comorbid conditions should be evaluated and addressed; this is generally feasible on an outpatient basis, though some patients will require admis Continue reading >>

Ectopic Fat And Insulin Resistance: Pathophysiology And Effect Of Diet And Lifestyle Interventions

Ectopic Fat And Insulin Resistance: Pathophysiology And Effect Of Diet And Lifestyle Interventions

International Journal of Endocrinology Volume 2012 (2012), Article ID 983814, 18 pages 1Departments of Endocrinology & Metabolism and General Internal Medicine, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands 2Walaeus Library, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands 3Department of Radiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands Academic Editor: Andreas Höflich Copyright © 2012 M. Snel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions. 1. Introduction The amount of people with obesity has increased dramatically over the past decades to an estimated number of 400 million adults worldwide with a projected 700 million in 2015 [1]. Obesity predisposes to the development of insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) [2–7]. However, about 30% of obese men and Continue reading >>

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