Soria B, Martín F, Andreu E, Sanchez-Andrés J V, Nacher V, Montana E
Department of Physiology, School of Medicine, University of Alicante, Spain.
Diabetes. 1996 Dec;45(12):1755-60. doi: 10.2337/diab.45.12.1755.
The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysiology of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+]i) of islets syngeneically transplanted into normal and streptozocin-induced diabetic mice. In both groups, normoglycemia was maintained after transplantation. Islets transplanted into normal recipients showed similar changes in beta-cell membrane potential and [Ca2+]i oscillations to those in control islets. In contrast, when islets were transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in control islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mmol/l). When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+]i oscillations were broader in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and higher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K+(ATP)) channels in transplanted islets that maintained normoglycemia with a limited beta-cell mass.
糖尿病患者胰岛移植效果不佳的原因尚不清楚；需要更好地了解移植胰岛的病理生理学。为了研究移植胰岛中促分泌素刺激与胰岛素释放之间的偶联机制，我们测定了葡萄糖、甲苯磺丁脲和氨甲酰胆碱对同基因移植到正常小鼠和链脲佐菌素诱导的糖尿病小鼠体内的胰岛β细胞膜电位和胞质钙浓度（[Ca2+]i）的影响。两组移植后均维持血糖正常。移植到正常受体的胰岛在β细胞膜电位和[Ca2+]i振荡方面表现出与对照胰岛相似的变化。相反，当胰岛移植到糖尿病小鼠体内时，与对照胰岛（11 mmol/l）相比，在较低葡萄糖浓度（5.6 mmol/l）时就会触发电活动爆发，并且在低于对照胰岛（22 mmol/l）的葡萄糖浓度（11 mmol/l）时达到最大电活动。当将膜电位绘制为葡萄糖浓度的函数时，剂量反应曲线向左移动。与对照胰岛相比，葡萄糖诱导的[Ca2+]i振荡持续时间更长（22.3±0.6秒对118.1±12.6秒；P<0.01）且幅度更高（135±36 nmol/l对352±36 nmol/l；P<0.01）。葡萄糖超敏性归因于移植胰岛中可阻断的ATP敏感性钾（K+(ATP)）通道比例的静息性降低，这些胰岛以有限的β细胞量维持血糖正常。
