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Type 2 Diabetes Mechanism

Pathogenesis Of Type 2 Diabetes Mellitus

Pathogenesis Of Type 2 Diabetes Mellitus

INTRODUCTION Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion. It is a common disorder with a prevalence that rises markedly with increasing degrees of obesity (figure 1) [1]. The prevalence of type 2 diabetes has risen alarmingly in the past decade [2], in large part linked to the trends in obesity and sedentary lifestyle [3]. PATHOPHYSIOLOGY Understanding the pathogenesis of type 2 diabetes is complicated by several factors [4]. Patients present with a combination of varying degrees of insulin resistance and relative insulin deficiency, and it is likely that both contribute to type 2 diabetes [5-7]. Furthermore, each of the clinical features can arise through genetic or environmental influences, making it difficult to determine the exact cause in an individual patient. Moreover, hyperglycemia itself can impair pancreatic beta-cell function and exacerbate insulin resistance, leading to a vicious cycle of hyperglycemia causing a worsening metabolic state [8]. Type 2 diabetes is often accompanied by other conditions, including hypertension, high serum low-density lipoprotein (LDL) cholesterol concentrations, and low serum high-density lipoprotein (HDL) cholesterol concentrations that, like type 2 diabetes, increase cardiovascular risk. This constellation of clinical conditions is referred to as the metabolic syndrome [9]. Hyperinsulinemia occurring in response to insulin resistance may play an important role in the genesis of these abnormalities. Increased free fatty acid levels, inflammatory cytokines from fat, and oxidative factors have all been implicated in the pathogenesis of metabolic syndrome, type 2 diabetes, and their cardiovascular complications. (See "The metabolic syndrome (insulin re Continue reading >>

Mechanisms And Therapeutic Targets In Type 2 Diabetes Mellitus - Sciencedirect

Mechanisms And Therapeutic Targets In Type 2 Diabetes Mellitus - Sciencedirect

Volume 1, Issue 2 , November 2004, Pages 151-157 Author links open overlay panel BrandyPanunti Ali A.Jawa Vivian A.Fonseca Get rights and content The pathogenesis of type 2 diabetes mellitus is multifactorial and complex, and it is influenced by both genetic and environmental factors. This metabolic disorder results from insulin resistance in target tissues and impairment of pancreatic insulin secretion. The purpose of this review is to examine our current understanding of the pathophysiology of type 2 diabetes, identify therapeutic targets, and highlight recent advances in addressing this complex disorder. Daniel J. Rader University of Pennsylvania Medical Center, USA The authors review the pathophysiology of type 2 diabetes mellitus, a condition which is rapidly increasing in prevalence and which is a major risk factor for macro- and microvascular disease. Insulin resistance and impairment of insulin secretion both contribute to the expression of type 2 diabetes, but a detailed understanding of the molecular pathophysiology of type 2 diabetes is gradually being elucidated. Ultimately, this information will undoubtedly lead to new therapies for the prevention and treatment of type 2 diabetes and its complications. Continue reading >>

Mechanisms In Endocrinology: Metabolic And Inflammatory Pathways On The Pathogenesis Of Type 2 Diabetes

Mechanisms In Endocrinology: Metabolic And Inflammatory Pathways On The Pathogenesis Of Type 2 Diabetes

Abstract Obesity is the main risk factor for type 2 diabetes (T2D). Studies performed over the last 20 years have identified inflammation as the most important link between these two diseases. During the development of obesity, there is activation of subclinical inflammatory activity in tissues involved in metabolism and energy homeostasis. Intracellular serine/threonine kinases activated in response to inflammatory factors can catalyse the inhibitory phosphorylation of key proteins of the insulin-signalling pathway, leading to insulin resistance. Moreover, during the progression of obesity and insulin resistance, the pancreatic islets are also affected by inflammation, contributing to β-cell failure and leading to the onset of T2D. In this review, we will present the main mechanisms involved in the activation of obesity-associated metabolic inflammation and discuss potential therapeutic opportunities that can be developed to treat obesity-associated metabolic diseases. Invited Author's profile L A Velloso MD, PhD is Professor of Medicine and Head of the Obesity and Co-Morbidities Research Center at the University of Campinas, Brazil. Professor Velloso's current research interests include characterization of the inflammatory mechanisms involved in the dysfunction of the hypothalamus in obesity. Introduction Type 2 diabetes (T2D) results from the combination of insulin resistance and a relative deficiency of insulin production (1). Despite the fact that both insulin resistance and insulin insufficiency may be induced by a number of factors that comprise genetic defects, sedentary lifestyle, dietary factors and endocrine disruptors, among others (1, 2, 3, 4, 5), inflammation has emerged as a unifying mechanism capable of affecting both the action and production of insuli Continue reading >>

Pathogenesis Of Type 2 Diabetes

Pathogenesis Of Type 2 Diabetes

Please confirm that you would like to log out of Medscape.If you log out, you will be required to enter your username and password the next time you visit. Log out Cancel Insulin resistance often is the primary metabolic abnormality leading to the development of type 2 diabetes. Type 2 diabetes can be viewed as the consequence of a series of pathophysiologic changes, each of which makes the patient vulnerable to subsequent disruption of normal glucose homeostasis. In most individuals, insulin resistance is the first of a sequence of abnormalities leading to the development of type 2 diabetes. Insulin resistance is compensated by increased insulin secretion (hyperinsulinemia), which allows glucose metabolism to remain normal. The beta cells in genetically susceptible individuals become impaired, leading to delayed and insufficient insulin secretion. Due to decreasing beta-cell function, the individual with insulin resistance first develops postprandial hyperglycemia and subsequently develops fasting hyperglycemia. Chronic hyperglycemia contributes to a further suppression of pancreatic beta-cell insulin secretion and worsens insulin resistance. These 3 components (insulin resistance, insulin deficiency, and glucose toxicity) are the targets of our therapeutic interventions. The distinction between insulin-sensitive and insulin-resistant type 2 diabetes is important when considering treatment. A drug that treats insulin resistance may be the drug of choice for an insulin-resistant patient, but should not be prescribed for a patient with insulin-sensitive diabetes. In the United States, nearly 30 million individuals have some form of glucose intolerance or diabetes (type 1 or, much more commonly, type 2).[ 1 ] Further breakdown of these numbers reveals critical facts for Continue reading >>

Diabetes Mellitus Type 2

Diabetes Mellitus Type 2

Diabetes mellitus type 2 (also known as type 2 diabetes) is a long-term metabolic disorder that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.[6] Common symptoms include increased thirst, frequent urination, and unexplained weight loss.[3] Symptoms may also include increased hunger, feeling tired, and sores that do not heal.[3] Often symptoms come on slowly.[6] Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations.[1] The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.[4][5] Type 2 diabetes primarily occurs as a result of obesity and lack of exercise.[1] Some people are more genetically at risk than others.[6] Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to diabetes mellitus type 1 and gestational diabetes.[1] In diabetes mellitus type 1 there is a lower total level of insulin to control blood glucose, due to an autoimmune induced loss of insulin-producing beta cells in the pancreas.[12][13] Diagnosis of diabetes is by blood tests such as fasting plasma glucose, oral glucose tolerance test, or glycated hemoglobin (A1C).[3] Type 2 diabetes is partly preventable by staying a normal weight, exercising regularly, and eating properly.[1] Treatment involves exercise and dietary changes.[1] If blood sugar levels are not adequately lowered, the medication metformin is typically recommended.[7][14] Many people may eventually also require insulin injections.[9] In those on insulin, routinely checking blood sugar levels is advised; however, this may not be needed in those taking pills.[15] Bariatri Continue reading >>

:: The Korean Journal Of Internal Medicine

:: The Korean Journal Of Internal Medicine

Keywords: Insulin resistance ; Type 2 diabetes ; Glucose transport ; Skeletal muscle A fundamental mechanism for the maintenance of glucose homeostasis is the rapid action of insulin to stimulate glucose uptake and metabolism in peripheral tissues. Skeletal muscle is the primary site of glucose disposal in the insulin-stimulated state [ 1 ]. Resistance to the actions of insulin in skeletal muscle is a major pathogenic factor in type 2 or type 1 diabetes mellitus [ 2 , 3 ]; it also contributes to the morbidity of obesity, and complicates poorly controlled type 1 (autoimmune) diabetes [ 2 ]. The ability of insulin to increase glucose transport in skeletal muscle is elicited by the translocation of glucose transporter 4 (Glut4), the major insulin regulated glucose transporter, from intracellular vesicles to the plasma membrane and transverse tubules [ 4 ]. In muscle of type 2 diabetic subjects, the expression of the Glut4 gene is normal, and impaired glucose uptake by insulin action most likely results from altered trafficking or impaired function of Glut4 [ 5 - 7 ]. Because glucose transport in response to other stimuli that use different signaling pathways is normal in muscle of type 2 diabetic subjects [ 4 ], the resistance to insulin stimulation may be due to impaired insulin signal transduction [ 8 ]. In this review, we mainly summarize the updated information on insulin signaling over the past decade, with particular emphasis on the molecular mechanism of human insulin resistance, and also address the physiological role of the newly identified player of insulin action. Insulin signaling involves a cascade of events initiated by insulin binding to its cell surface receptor, followed by receptor autophosphorylation, and activation of receptor tyrosine kinases, which r Continue reading >>

Key Mechanism Involved In Type 2 Diabetes Identified

Key Mechanism Involved In Type 2 Diabetes Identified

Follow all of ScienceDaily's latest research news and top science headlines ! Key mechanism involved in Type 2 diabetes identified Scientists have discovered a key protein that regulates insulin resistance -- the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes. This breakthrough points to a new way to potentially treat or forestall Type 2 diabetes, a rapidly growing global health problem. Scientists at the Gladstone Institutes have discovered a key protein that regulates insulin resistance -- the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes. This breakthrough points to a new way to potentially treat or forestall type 2 diabetes, a rapidly growing global health problem. In a paper being published online this week in the Proceedings of the National Academy of Sciences, researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, describe an unexpected role of the p75 neurotrophin receptor in controlling how the body processes sugar. Called p75NTR, this receptor protein is usually associated with functions in neurons. "We identified that p75NTR is a unique player in glucose metabolism," said Dr. Akassoglou, who is also an associate professor of neurology at the University of California, San Francisco, with which Gladstone is affiliated. "Therapies targeted at p75NTR may represent a new therapeutic approach for diabetes." The pancreas makes a hormone called insulin that processes glucose, moving it from the bloodstream into the body's cells where it is used for energy. Insulin resistance is a key feature of Type 2 diabetes, in which glucose builds up in the b Continue reading >>

Metabolic Mechanisms In Obesity And Type 2 Diabetes: Insights From Bariatric/metabolic Surgery

Metabolic Mechanisms In Obesity And Type 2 Diabetes: Insights From Bariatric/metabolic Surgery

Abstract Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery. © 2015 S. Karger GmbH, Freiburg Introduction Obesity has become a real concern worldwide due to its increasing prevalence and to the associated cluster of diseases that reduce life quality and expectancy. Patients with BMI over 40 kg/m² as well as those with a BMI over 35 kg/m² and comorbidities, who have failed to obtain and maintain significant weight reduction through nonsurgical means, are submitted to bariatric surgery in order to reach the weight goals [1]. Type 2 diabetes mellitus (T2DM) is the major comorbidity of obesity, and therefore the terms ‘diabesity' and Continue reading >>

Mechanisms Linking Obesity To Insulin Resistance And Type 2 Diabetes

Mechanisms Linking Obesity To Insulin Resistance And Type 2 Diabetes

Mechanisms linking obesity to insulin resistance and type 2 diabetes Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet -cells the cells that release insulin failure to control blood glucose levels results. Abnormalities in -cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention. Prevalence of overweight and obesity among US children, adolescents, and adults, 19992002 . J. Am. Med. Assoc. 291, 28472850 (2004). Wild, S., Roglic, G., Green, A., Sicree, R. & King, H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 Role of insulin resistance in human disease Plasma insulin responses to glucose and tolbutamide of normal weight and obese diabetic and nondiabetic subjects Polonsky, K. S., Given, B. D. & Van Cauter, E. Twenty-four-hour profiles and patterns of insulin secretion in normal and obese subjects Quantification of the relationship between insulin sensitivity and B-cell function in human subjects. Evidence for a hyperbolic function The importance of -cell failure in the development and progression of type 2 diabetes . J. Clin. Endocrinol. Metab. 86, 40474058 (2001). Insulin resistance during puberty: results from clamp studies in 357 children Buchanan, T. A., Metzger, B. E., Freinkel, N. & Bergman, R. N. Insulin sensitiv Continue reading >>

Novel Mechanism Of Insulin Resistance In Type 2 Diabetes

Novel Mechanism Of Insulin Resistance In Type 2 Diabetes

Novel mechanism of insulin resistance in type 2 diabetes Published 2015-09-17 18:05. Updated 2015-09-22 13:05 Denna sida p svenska Insensitivity to insulin, also called insulin resistance, is associated with type 2 diabetes and affects several cell types and organs in the body. Now, scientists from Swedens Karolinska Institutet have discovered a mechanism that explains how insulin-producing cells can be insulin resistant and insulin sensitive at the same time. The findings are being published in the journal Cell Reports, and may lead to future novel treatment strategies for type 2 diabetes. Insulin is critical in lowering blood glucose concentration. Individuals with type 2 diabetes suffer from insulin resistance and this means that their cells/organs are insensitive to insulin. In type 2 diabetes the body tries to compensate by producing more insulin, and also by increasing the number of insulin-producing cells. Finding new treatment strategies is only possible by gaining a greater understanding of what happens in the body of a diabetic patient. One scientific challenge is to explain how a cell/organ at the same time can be insulin resistant in one biological function and insulin sensitive in another. Drs Barbara Leibiger and Ingo Leibiger , both members of Professor Per-Olof Berggrens research group at the Department of Molecular Medicine and Surgery , Karolinska Institutet, are particularly interested in the insulin-producing beta cells. The beta cell must have insulin to work properly, says Barbara Leibiger, PhD, Associate Professor, and lead author of the current study. In a person with diabetes, the beta cells become insensitive to insulin. The researchers have previously shown that the beta cell has two receptors with different biological functions, insulin rece Continue reading >>

What Causes Type 2 Diabetes?

What Causes Type 2 Diabetes?

Insulin resistance and high levels of insulin and lipids all precede the development of metabolic dysfunction. Which metabolic factor is to blame? Type 2 diabetes is a multifactorial metabolic disease.1 Obesity, elevated levels of lipids and insulin in the blood, and insulin resistance all accompany the elevated blood glucose that defines diabetes. (Diabetes is defined as fasting blood glucose concentrations above 7 millimolar (mM), or above 11 mM two hours after ingestion of 75 grams of glucose.) But while researchers have made much progress in understanding these components of the metabolic dysfunction, one major question remains: What serves as the primary driver of disease? Lifestyle choices characterized by inactivity have been postulated as one possible cause. Researchers have also pointed the finger at nutrition, postulating that poor food choices can contribute to metabolic disease. However, there is thus far weak support for these hypotheses. Changing to a healthy diet typically does not result in significant weight loss or the resolution of metabolic dysfunction, and it is rare to reverse obesity or diabetes through increased exercise. Furthermore, there does not appear to be a strong relationship between body-mass index (BMI) and activity level, though exercise clearly has many other health benefits. With such macroscale factors unable to explain most cases of obesity and diabetes, scientists have looked to molecular mechanisms for answers. There are at least 40 genetic mutations known to be associated with type 2 diabetes. These genes tend to be involved in the function of pancreatic β cells, which secrete insulin in response to elevated levels of the three types of cellular fuel: sugar, fat, and protein. In healthy young adults, circulating glucose concent Continue reading >>

Diabetes: Mechanism, Pathophysiology And Management-a Review

Diabetes: Mechanism, Pathophysiology And Management-a Review

Anees A Siddiqui1*, Shadab A Siddiqui2, Suhail Ahmad, Seemi Siddiqui3, Iftikhar Ahsan1, Kapendra Sahu1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi (INDIA)-110062. School of Pharmacy, KIET, Ghaziabad U.P. SGC college of Pharmacy, Baghpat(UP) Corresponding Author:Anees A Siddiqui E-mail: [email protected] Received: 20 February 2011 Accepted: 02 May 2011 Citation: Anees A Siddiqui, Shadab A Siddiqui, Suhail Ahmad, Seemi Siddiqui, Iftikhar Ahsan, Kapendra Sahu “Diabetes: Mechanism, Pathophysiology and Management-A Review” Int. J. Drug Dev. & Res., April-June 2013, 5(2): 1-23. Copyright: © 2013 IJDDR, Anees A Siddiqui et al. This is an open access paper distributed under the copyright agreement with Serials Publication, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Related article at Pubmed, Scholar Google Visit for more related articles at International Journal of Drug Development and Research The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. Over the last three decades, the status of diabetes has been changed, earlier it was considered as a mild disorder of the elderly people. Now it becomes a major cause of morbidity and mortality affecting the youth and middle aged people. According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The main force of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity a Continue reading >>

Mechanisms Of Action Of Hydroxychloroquine In Reducing Risk Of Type 2 Diabetes Toledo, Frederico G. S. University Of Pittsburgh, Pittsburgh, Pa, United States

Mechanisms Of Action Of Hydroxychloroquine In Reducing Risk Of Type 2 Diabetes Toledo, Frederico G. S. University Of Pittsburgh, Pittsburgh, Pa, United States

Mechanisms of Action of Hydroxychloroquine in Reducing Risk of Type 2 Diabetes Mechanisms of Action of Hydroxychloroquine in Reducing Risk of Type 2 Diabetes. Diabetes is approaching epidemic proportions in the United States. Efforts to implement effective strategies for diabetes prevention have been limited by poor long-term adherence to lifestyle modifications and potential side effects and costs of pharmacologic interventions. We recently showed that long-term use of hydroxychloroquine (HCQ), an antimalarial used to treat rheumatoid arthritis is associated with an impressive 77% reduction in risk of diabetes when taken for more than 4 years. This protective association increases with greater duration of use. In patients with well established Type 2 diabetes mellitus (T2DM), HCQ has a positive effect on glycemic control. In spite of its efficacy and excellent safety profile, HCQ is not used to treat T2DM because of potential retinal toxicity, a very rare though feared side effect unrelated to vascular disease or T2DM. The precise mechanism(s) by which HCQ attenuates diabetes risk have not been determined. Here we propose a pilot and feasibility clinical trial of HCQ in subjects with pre-diabetes. In this pilot and feasibility clinical trial, we will study changes in beta-cell function (insulin secretion) and insulin sensitivity associated with short-term HCQ therapy compared with placebo using frequent sampling intravenous glucose tolerance testing (FSIGTT) methodology. We propose to 1) determine the short-term effects of HCQ (600 mg/d orally) on beta-cell function, insulin disposition index, and insulin sensitivity in subjects with pre-diabetes and 2) determine the change in insulin secretion, disposition index and sensitivity 3 months after HCQ cessation. Thirty ov 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 >>

Molecular Mechanisms Of Insulin Resistance In Type 2 Diabetes Mellitus

Molecular Mechanisms Of Insulin Resistance In Type 2 Diabetes Mellitus

Molecular mechanisms of insulin resistance in type 2 diabetes mellitus Vandana Saini, Department of Biochemistry, Lady Hardinge Medical College, New Delhi 110001, India. Author contributions: Saini V contributed solely to this work. Correspondence to: Vandana Saini, MD, Department of Biochemistry, Lady Hardinge Medical College, New Delhi 110001, India. [email protected] Received 2010 Jan 18; Revised 2010 Jun 22; Accepted 2010 Jun 29. Copyright 2010 Baishideng Publishing Group Co., Limited. All rights reserved. This article has been cited by other articles in PMC. Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear. It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade, which leads to defects in insulin signaling downstream to the insulin receptor. In addition, the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin. Among the many molecules involved in the intracellular processing of the signal provided by insulin, the insulin receptor substrate-2, the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest, as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo. Recently, studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase C causes a reduction in insulin receptor gene expression. Additionally, it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases, and weakens insulin signal transduction. Thus, in this review, the current developmen Continue reading >>

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