A novel cellular defect in diabetes: membrane repair failure

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 (INS2Akita+/2) 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 as-sessed in diabetic mice after downhill running, which induces myocyte plasma membrane disruption injuries in vivo. A cell cul-ture model was used to investigate the role of advanced glycation end products (AGEs) and the receptor for AGE (RAGE) in de-velopment of this repair defect. RESULTS—Diabetic myocytes displayed significantly more dy