A novel cellular defect in diabetes: Membrane repair failure

Amber C. Howard, Anna K. McNeil, Fei Xiong, Wen Cheng Xiong, Paul L. McNeil

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36 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3034-3043
Number of pages10
JournalDiabetes
Volume60
Issue number11
DOIs
StatePublished - Nov 1 2011

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Howard, A. C., McNeil, A. K., Xiong, F., Xiong, W. C., & McNeil, P. L. (2011). A novel cellular defect in diabetes: Membrane repair failure. Diabetes, 60(11), 3034-3043. https://doi.org/10.2337/db11-0851