摘要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 Ca2+ 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,Ca2+ 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 Ca2+ channel activities,L-type and store-operated Ca2+ (SOC),were evaluated using whole-cell patch-clamp recording.The glucose induced Ca2+ 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.Ca2+ channel activity was increased and glucose induced Ca2+ influx was impaired,but could be recovered by genipin.Conclusion Defective mitochondrial function in diabetic mice pancreatic beta cells is a key cause of abnormal insulin secretion by altering Ca2+ influx,but not via Ca2+ channel activity.
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