STIMULATION OF INSULIN RELEASE IN ISOLATED RAT ISLETS BY GIP IN PHYSIOLOGICAL CONCENTRATIONS AND ITS RELATION TO ISLET CYCLIC-AMP CONTENT
STIMULATION OF INSULIN RELEASE IN ISOLATED RAT ISLETS BY GIP IN PHYSIOLOGICAL CONCENTRATIONS AND ITS RELATION TO ISLET CYCLIC-AMP CONTENT
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DOI：
10.1007/bf00291078
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发表时间：
1985-01-01
期刊：
影响因子：
8.2
通讯作者：
CREUTZFELDT, W
中科院分区：
文献类型：
--
作者：
SIEGEL, EG;CREUTZFELDT, W
几种促胰岛素激素已被证明能增加孤立胰岛中环磷酸腺苷的水平。本研究旨在研究胃抑制多肽(葡萄糖依赖的胰岛素释放多肽)是否具有类似的作用，特别是在接近血液生理水平的浓度下。胶原酶分离的大鼠胰岛在组织培养(199)中维持24小时，然后孵育30分钟，测定胰岛素释放和环磷酸腺苷含量。胃抑制多肽1~100 ng/ml(0.196~19.6nmol/L)可剂量依赖性地促进葡萄糖诱导的胰岛素释放(16.7mmoL/L)。1 0 0 ng/ml的磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤存在时，即使1 ng/ml的胃抑制性多肽也能增加环磷酸腺苷的含量和胰岛素的释放。这种激素的浓度可以在用餐后在人的血液中测量到。在新鲜分离的胰岛中，在1~100 ng/ml的浓度范围内，未检测到激素对葡萄糖诱导的胰岛素释放或环磷酸腺苷含量的影响。这些结果表明，在组织培养中短期维持可显著提高分离胰岛的激素敏感性。结果提示，胃抑制性多肽引起环磷酸腺苷的升高，可能与激素的促胰岛素作用有关。
Several insulinotropic hormones have been shown to increase the level of cyclic AMP in isolated islets. This study was performed to investigate whether gastric inhibitory polypeptide (glucose-dependent insulin-releasing polypeptide) has a similar effect, in particular at concentrations close to the physiological level in blood. Collagenase isolated rat islets were maintained for 24 h in tissue culture (medium 199) and then incubated for 30 min for measurement of insulin release and cyclic AMP content. Glucose-induced (16.7 mmol/l) insulin release was enhanced by gastric inhibitory polypeptide 1-100 ng/ml (0.196-19.6 nmol/l) in a dose-related fashion. The cyclic AMP content was enhanced only by 100 ng/ml. However, when 0.1 mmol/l of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine was present, even 1 ng/ml of gastric inhibitory polypeptide increased both cyclic AMP content and insulin release. Such a concentration of the hormone can be measured in human blood after a meal. In contrast, in freshly isolated islets no effect of the hormone on glucose-induced insulin release or cyclic AMP content could be detected for concentrations ranging from 1 to 100 ng/ml. These findings demonstrate that the hormone sensitivity of isolated islets is markedly enhanced by short-term maintenance in tissue culture. The results suggest that an increase in cyclic AMP is seen in response to gastric inhibitory polypeptide and may be causally related to the insulinotropic effect of the hormone.