title: Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells.
abstract: BACKGROUND
  Abnormal insulin secretion of pancreatic beta cells is now regarded as the more primary defect than the insulin function in the etiology of type 2 diabetes. Previous studies found impaired mitochondrial function and impaired Ca(2+) influx in beta cells in diabetic patients and animal models, suggesting a role for these processes in proper insulin secretion. The aim of this study was to investigate the detailed relationship of mitochondrial function, Ca(2+) influx, and defective insulin secretion.
  
  
  METHODS
  We investigated mitochondrial function and morphology in pancreatic beta cell of diabetic KK-Ay mice and C57BL/6J mice. Two types of Ca(2+) channel activities, L-type and store-operated Ca(2+) (SOC), were evaluated using whole-cell patch-clamp recording. The glucose induced Ca(2+) influx was measured by a non-invasive micro-test technique (NMT).
  
  
  RESULTS
  Mitochondria in KK-Ay mice pancreatic beta cells were swollen with disordered cristae, and mitochondrial function decreased compared with C57BL/6J mice. Ca(2+) channel activity was increased and glucose induced Ca(2+) influx was impaired, but could be recovered by genipin.
  
  
  CONCLUSIONS
  Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca(2+) influx, but not via Ca(2+) channel activity.
authors.affiliation: Department of General Surgery, Digestive Medical Center, the First Affiliated Hospital, Medical School, Tsinghua University, Beijing 100016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: D Marshall
authors.initials: DM
authors.lastname: Porterfield
authors.forename: Xi-Yan
authors.initials: XY
authors.lastname: Zheng
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: Zong-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000503:physiopathology; D004594:Electrophysiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D007328:Insulin; D002118:Calcium