Hellman B, Berne C, Grapengiesser E, Grill V, Gylfe E, Lund P E
Department of Medical Cell Biology, University of Uppsala, Sweden.
Eur J Clin Invest. 1990 Oct;20 Suppl 1:S10-7. doi: 10.1111/j.1365-2362.1990.tb01771.x.
The effects of glucose on the cytoplasmic Ca2+ concentration (Ca2+i) regulating insulin release were investigated using pancreatic beta-cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca2+i followed by a rise, often manifested as high amplitude oscillations. The Ca2+i-lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the beta-cells were already depolarized by tolbutamide. Glucose-induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin- and noninsulin-dependent diabetes mellitus. Brief exposure of beta-cells to 2.2 mmol l-1 streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca2+i. The results indicate that glucose-induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defects in diabetes mellitus.
利用代表正常和糖尿病情况的胰腺β细胞，研究了葡萄糖对调节胰岛素释放的细胞质Ca2+浓度（Ca2+i）的影响。葡萄糖浓度的增加导致Ca2+i略有下降，随后上升，常表现为高幅度振荡。当β细胞已被甲苯磺丁脲去极化时，与胰岛素释放抑制相关的葡萄糖作用中Ca2+i降低成分变得尤为突出。在链脲佐菌素或四氧嘧啶诱导糖尿病的大鼠实验中也观察到葡萄糖诱导的胰岛素释放抑制。其他研究表明，胰岛素依赖型和非胰岛素依赖型糖尿病患者静脉注射葡萄糖后血浆胰岛素水平降低。β细胞短暂暴露于2.2 mmol l-1链脲佐菌素会导致对葡萄糖反应受损，表现为Ca2+i周期性变化消失。结果表明，葡萄糖诱导的去极化是一个易受影响的过程，其干扰可能导致糖尿病患者胰岛素分泌缺陷。
