Zawalich W S, Bonnet-Eymard M, Zawalich K C
Yale University School of Nursing, New Haven, Connecticut 06536-0740, USA.
Am J Physiol. 1998 Dec;275(6):E917-24. doi: 10.1152/ajpendo.1998.275.6.E917.
The capacity of 20 mM glucose to desensitize insulin release was determined. A prior exposure to 20 mM glucose impaired the response of rat islets to subsequent restimulation. Compared with control islets, insulin secretory rates measured 25-30 min after the onset of 20 mM glucose stimulation were reduced by 75%. Restimulation of glucose-desensitized islets with 20 mM glucose plus 500 nM forskolin resulted in a dramatic enhancement of both phases of secretion. In contrast to the desensitization of rat islets induced by prior 20 mM glucose exposure, mouse islets were immune to this adverse effect of the hexose. Prior exposure to 20 mM glucose had no adverse effect on glucose usage rates. The activation of phospholipase C in glucose-desensitized rat islets was compromised when compared with control islets. The impairment could not be accounted for by a decrease in immunoreactive content of several major phospholipase C isozymes (beta1 or delta1) or their partitioning between the membrane and cytosolic compartments. In contrast to rat islets, prior exposure of mouse islets to 20 mM glucose for 180 min had no effect on inositol phosphate accumulation. These observations document an additional difference between rat and mouse islets and suggest that the evolution of desensitization is a consequence of the impaired activation of phospholipase C in rat islets.
测定了20 mM葡萄糖使胰岛素释放脱敏的能力。预先暴露于20 mM葡萄糖会损害大鼠胰岛对随后再刺激的反应。与对照胰岛相比，在20 mM葡萄糖刺激开始后25 - 30分钟测量的胰岛素分泌率降低了75%。用20 mM葡萄糖加500 nM福司可林对葡萄糖脱敏的胰岛进行再刺激，导致两个分泌阶段都显著增强。与预先暴露于20 mM葡萄糖诱导的大鼠胰岛脱敏相反，小鼠胰岛对这种己糖的不利影响具有抗性。预先暴露于20 mM葡萄糖对葡萄糖利用率没有不利影响。与对照胰岛相比，葡萄糖脱敏的大鼠胰岛中磷脂酶C的激活受到损害。这种损害不能用几种主要磷脂酶C同工酶（β1或δ1）的免疫反应性含量降低或它们在膜和胞质区室之间的分配来解释。与大鼠胰岛相反，预先将小鼠胰岛暴露于20 mM葡萄糖180分钟对肌醇磷酸积累没有影响。这些观察结果记录了大鼠和小鼠胰岛之间的另一个差异，并表明脱敏的演变是大鼠胰岛中磷脂酶C激活受损的结果。
