Department of General Surgery, Digestive Medical Center, the First Affiliated Hospital, Medical School, Tsinghua University, Beijing 100016, China.
Chin Med J (Engl). 2012 Feb;125(3):502-10.
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.
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).
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.
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.
目前，人们认为胰腺β细胞异常的胰岛素分泌比 2 型糖尿病病因中的胰岛素功能更为原发性缺陷。先前的研究发现，糖尿病患者和动物模型的β细胞中线粒体功能受损和 Ca(2+)内流受损，这表明这些过程在适当的胰岛素分泌中起作用。本研究旨在探讨线粒体功能、Ca(2+)内流和胰岛素分泌缺陷之间的详细关系。
我们研究了糖尿病 KK-Ay 小鼠和 C57BL/6J 小鼠的胰岛β细胞中线粒体功能和形态。使用全细胞膜片钳记录评估两种类型的 Ca(2+)通道活性，即 L 型和储存操纵的 Ca(2+)（SOC）。通过非侵入性微测试技术（NMT）测量葡萄糖诱导的 Ca(2+)内流。
KK-Ay 小鼠胰岛β细胞中的线粒体肿胀，嵴排列紊乱，与 C57BL/6J 小鼠相比，线粒体功能下降。Ca(2+)通道活性增加，葡萄糖诱导的 Ca(2+)内流受损，但可被京尼平恢复。
糖尿病小鼠胰岛β细胞中线粒体功能缺陷是通过改变 Ca(2+)内流而不是通过 Ca(2+)通道活性导致异常胰岛素分泌的关键原因。
