title: A novel cellular defect in diabetes: membrane repair failure.
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.
  
  
  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.
authors.affiliation: Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, Georgia, USA.
authors.forename: Amber C
authors.initials: AC
authors.lastname: Howard
authors.forename: Anna K
authors.initials: AK
authors.lastname: McNeil
authors.forename: Fei
authors.initials: F
authors.lastname: Xiong
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
authors.forename: Paul L
authors.initials: PL
authors.lastname: McNeil
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005456:Fluorescent Dyes / Q000378:metabolism / Q000633:toxicity; D017127:Glycation End Products, Advanced / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism; D007834:Lasers / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D009135:Muscular Diseases / Q000378:metabolism* / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000378:metabolism; D009336:Necrosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic