| Over-nutrition, obesity and insulin resistance in the development of β cell dysfunction. | |
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MedLine Citation:
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PMID: 22229253 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The incidence of type 2 diabetes mellitus (DM2) has increased dramatically over the last several decades, largely driven by equally worrisome growing rates of obesity. Chronic diabetic complications are leading causes of morbidity and mortality worldwide. Key players in the pathophysiology of DM2 are insulin resistance and β cell dysfunction, which in turn is a result of both β cell functional abnormality as well as reduced β cell mass. The mechanisms implicated are multifactorial and include genetic and environmental factors leading to obesity. Glucose homeostasis is critically dependent on a finely regulated balance between insulin sensitivity and output in the pancreas, and insulin resistance demands a corresponding rise in insulin output in order to maintain normal glycemia. However, this compensation is lost in individuals predisposed to DM2, resulting in overt hyperglycemia. Furthermore, insulin resistance related to excess adiposity is linked to several abnormalities which impact β cell function and viability. These include glucotoxicity, lipotoxicity, increased oxidative stress, and inflammation. In addition, insulin signaling in the β cell is essential to its own functionality and viability, and obesity-related abnormalities in insulin signaling are known to induce failure of insulin secretion and hyperglycemia. Insulin resistance in the β cell arises from defects in phosphorylation/activation of insulin receptor substrates (IRS) proteins, which result in impairment in glucose sensing, glucose stimulated insulin secretion, and also in increased loss of β cells. This review intends to provide an update on the main characteristics and mechanisms that link obesity and insulin resistance to β cell dysfunction in the pathogenesis of DM2. |
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Authors:
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Deepashree Gupta; Charles B Krueger; Guido Lastra |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: Current diabetes reviews Volume: 8 ISSN: 1875-6417 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101253260 Medline TA: Curr Diabetes Rev Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Missouri School of Medicine, One, Hospital Drive, Columbia, MO 65203, USA. guptad@health.missouri.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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