Xia M, Laychock S G
Department of Pharmacology and Therapeutics, State University of New York at Buffalo, School of Medicine.
Diabetes. 1993 Oct;42(10):1392-400. doi: 10.2337/diab.42.10.1392.
Glucose-induced insulin secretion is desensitized during long-term exposure of pancreatic islet beta-cells to elevated glucose levels. This study characterizes an in vitro model of glucose-induced desensitization in cultured isolated islets of the rat. Insulin secretion in desensitized islets cultured with 11 mM glucose for 4-7 days was progressively reduced compared with the normal freshly isolated (fresh) islets. When desensitized islets were returned to a basal concentration of glucose (5.5 mM) for up to 2 h, the glucose sensitivity of insulin secretion was restored to normal (recovered islets). Carbachol and L-arginine also reversed the effects of desensitization. However, basal insulin release was elevated in desensitized and recovered islets. Sodium-dependent myo-inositol uptake was reduced during desensitization by up to 49% within 4 days. myo-Inositol uptake was restored to normal in a time-dependent manner during recovery of islets at 5.5 mM glucose. The recovery of myo-inositol uptake paralleled that of insulin release. The apparent transport constant for myo-inositol uptake was significantly increased during desensitization, whereas the maximum uptake was not changed. myo-Inositol supplementation (35 or 250 microM) during islet culture did not alter myo-inositol uptake or insulin secretion in desensitized islets. Na(+)-K(+)-ATPase activity, but not 5'-nucleotidase activity, in desensitized islets was also inhibited by 65 and 47% when compared with fresh islet and recovered islet Na(+)-K(+)-ATPase activity, respectively. Thus, cultured islets represent an appropriate model to study biochemical parameters associated with the onset and reversibility of glucose desensitization of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
在胰岛β细胞长期暴露于升高的葡萄糖水平期间，葡萄糖诱导的胰岛素分泌会发生脱敏。本研究描述了大鼠培养的分离胰岛中葡萄糖诱导脱敏的体外模型。与正常新鲜分离的（新鲜）胰岛相比，用11 mM葡萄糖培养4 - 7天的脱敏胰岛中的胰岛素分泌逐渐减少。当脱敏胰岛恢复到基础葡萄糖浓度（5.5 mM）长达2小时时，胰岛素分泌的葡萄糖敏感性恢复正常（恢复的胰岛）。卡巴胆碱和L - 精氨酸也可逆转脱敏作用。然而，脱敏和恢复的胰岛中基础胰岛素释放增加。在脱敏过程中，钠依赖性肌醇摄取在4天内最多降低49%。在5.5 mM葡萄糖条件下胰岛恢复过程中，肌醇摄取以时间依赖性方式恢复正常。肌醇摄取的恢复与胰岛素释放的恢复平行。脱敏期间肌醇摄取的表观转运常数显著增加，而最大摄取量未改变。胰岛培养期间补充肌醇（35或250 microM）不会改变脱敏胰岛中的肌醇摄取或胰岛素分泌。与新鲜胰岛和恢复胰岛的Na(+)-K(+)-ATP酶活性相比，脱敏胰岛中的Na(+)-K(+)-ATP酶活性分别被抑制65%和47%，而5'-核苷酸酶活性未受影响。因此，培养的胰岛是研究与胰岛素分泌的葡萄糖脱敏的发生和可逆性相关的生化参数的合适模型。（摘要截短至250字）
