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衰老过程中的刺激-分泌偶联与胰岛素分泌:葡萄糖氧化及ATP敏感性钾通道反应性评估

Stimulus-secretion coupling and insulin secretion in aging: evaluation of glucose oxidation and ATP-sensitive potassium channel responsiveness.

作者信息

Ruhe R C, Curry D L, McDonald R B

机构信息

Departments of Nutrition, University of California, Davis 95616.

出版信息

Mech Ageing Dev. 1993 Oct 15;71(3):161-7. doi: 10.1016/0047-6374(93)90081-2.

DOI:10.1016/0047-6374(93)90081-2
PMID:8133674
Abstract

The purpose of this study was to evaluate possible age-related alterations in the glucose-stimulus/insulin-secretion coupling mechanism of islets of Langerhans. To this end, the interaction among insulin secretion, glucose oxidation, and ATP-sensitive potassium (K ATP) channel responsiveness was determined in islets of Langerhans isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Groups of 20 islets were incubated for 40 min at 37 degrees C in a buffer containing: (1) either 1.7 or 11.1 mM glucose; (2) 1.2 microM glyburide and either 1.7 or 11.1 mM glucose; (3) 5 microM epinephrine and 11.1 mM glucose; or (4) 1.2 microM glyburide, 5 microM epinephrine, and either 1.7 or 11.1 mM glucose. Insulin release of islets incubated in the presence of glyburide and 1.7 or 11.1 mM glucose was greater than that of islets incubated in glucose alone, while glucose oxidation did not increase. Epinephrine inhibited insulin release and glucose oxidation at 11.1 mM glucose and abolished glyburide-enhanced insulin release at 11.1 mM glucose. No effect of age was observed in any of the treatment categories. These results indicate that if age-related alterations are occurring in glucose-stimulus/insulin-secretion coupling, then such alterations are not associated with changes in K ATP channel-mediated responsiveness.

摘要

本研究的目的是评估胰岛葡萄糖刺激/胰岛素分泌偶联机制中可能存在的与年龄相关的改变。为此,测定了从6个月、12个月和26个月大的雄性Fischer 344(F344)大鼠分离的胰岛中胰岛素分泌、葡萄糖氧化和ATP敏感性钾(KATP)通道反应性之间的相互作用。将20个胰岛为一组,在含有以下成分的缓冲液中于37℃孵育40分钟:(1)1.7或11.1 mM葡萄糖;(2)1.2 μM格列本脲和1.7或11.1 mM葡萄糖;(3)5 μM肾上腺素和11.1 mM葡萄糖;或(4)1.2 μM格列本脲、5 μM肾上腺素和1.7或11.1 mM葡萄糖。在格列本脲和1.7或11.1 mM葡萄糖存在下孵育的胰岛的胰岛素释放量大于仅在葡萄糖中孵育的胰岛,而葡萄糖氧化并未增加。肾上腺素在11.1 mM葡萄糖时抑制胰岛素释放和葡萄糖氧化,并消除了11.1 mM葡萄糖时格列本脲增强的胰岛素释放。在任何治疗类别中均未观察到年龄的影响。这些结果表明,如果在葡萄糖刺激/胰岛素分泌偶联中发生与年龄相关的改变,那么这种改变与KATP通道介导的反应性变化无关。

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