Abnormal mitochondrial function impairs calcium influx in diabetic mouse pancreatic beta cells

作者：Li Fei; Porterfield D Marshall; Zheng Xi yan; Wang Wen jun; Xu Yue; Zhang Zong ming^*

来源：Chinese Medical Journal, 2012, 125(3): 502-510.

DOI：10.3760/cma.j.issn.0366-6999.2012.03.019

• type 2 diabetes
• pancreatic beta cell
• insulin secretion
• Ca2+ influx
• mitochondrial function

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 C57BU6J 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 C57BU6J 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. Chin Med J 2012;125(3):502-510

• 出版日期2012-2-5
• 单位清华大学