| A novel cellular defect in diabetes: membrane repair failure. | |
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MedLine Citation:
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PMID: 21940783 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Skeletal muscle myopathy is a common diabetes complication. One possible cause of myopathy is myocyte failure to repair contraction-generated plasma membrane injuries. Here, we test the hypothesis that diabetes induces a repair defect in skeletal muscle myocytes. RESEARCH DESIGN AND METHODS: Myocytes in intact muscle from type 1 (INS2(Akita+/-)) and type 2 (db/db) diabetic mice were injured with a laser and dye uptake imaged confocally to test repair efficiency. Membrane repair defects were also assessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell culture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in development of this repair defect. RESULTS: Diabetic myocytes displayed significantly more dye influx after laser injury than controls, indicating a repair deficiency. Downhill running also resulted in a higher level of repair failure in diabetic mice. This repair defect was mimicked in cultured cells by prolonged exposure to high glucose. Inhibition of the formation of AGE eliminated this glucose-induced repair defect. However, a repair defect could be induced, in the absence of high glucose, by enhancing AGE binding to RAGE, or simply by increasing cell exposure to AGE. CONCLUSIONS: Because one consequence of repair failure is rapid cell death (via necrosis), our demonstration that repair fails in diabetes suggests a new mechanism by which myopathy develops in diabetes. |
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Authors:
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Amber C Howard; Anna K McNeil; Fei Xiong; Wen-Cheng Xiong; Paul L McNeil |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-22 |
Journal Detail:
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Title: Diabetes Volume: 60 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-25 Completed Date: 2011-12-14 Revised Date: 2012-04-26 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
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Languages: eng Pagination: 3034-43 Citation Subset: AIM; IM |
Affiliation:
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Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, Georgia, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Membrane / drug effects, metabolism*, radiation effects, ultrastructure Cells, Cultured Diabetes Mellitus, Type 1 / complications* Diabetes Mellitus, Type 2 / complications* Fluorescent Dyes / metabolism, toxicity Glycosylation End Products, Advanced / adverse effects, antagonists & inhibitors, metabolism Hyperglycemia / metabolism Lasers / adverse effects Mice Mice, Inbred C57BL Mice, Mutant Strains Motor Activity Muscle Fibers, Skeletal / drug effects, metabolism*, radiation effects, ultrastructure Muscular Diseases / metabolism*, pathology Myoblasts, Skeletal / metabolism Necrosis Receptors, Immunologic / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R21 DK090703/DK/NIDDK NIH HHS; R21-DK-090703-01A1/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 0/Glycosylation End Products, Advanced; 0/Receptors, Immunologic; 0/advanced glycosylation end-product receptor |
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