PANCREATIC BETA-CELL RECOGNITION OF INSULIN SECRETAGOGUES - DOES CYCLIC-AMP MEDIATE EFFECT OF GLUCOSE
PANCREATIC BETA-CELL RECOGNITION OF INSULIN SECRETAGOGUES - DOES CYCLIC-AMP MEDIATE EFFECT OF GLUCOSE
复制标题
DOI：
10.1073/pnas.71.9.3405
复制
发表时间：
1974-01-01
影响因子：
11.1
通讯作者：
TALJEDAL, IB
中科院分区：
文献类型：
--
作者：
HELLMAN, B;IDAHL, LA;TALJEDAL, IB
研究了非肥胖小鼠胰岛微解剖后胰岛素释放和cAMP含量的变化。在缺乏3-异丁基-1-甲基黄嘌呤（一种磷酸二酯酶抑制剂）的情况下，20mm葡萄糖对cAMP没有影响，只有通过冷冻停止灌注技术才能检测到非常小的初始升高。然而，与甲基黄嘌呤结合，20 mM葡萄糖在周围胰岛和在封闭小瓶中常规培养的胰岛中产生显著的cAMP增加。葡萄糖与d -甘油醛和1,3-二羟基丙酮共享这种提高cAMP水平的能力。异丁基甲基黄嘌呤（0.05 ~ 1.0 mM）或5 μg/ml霍乱毒素（腺苷酸环化酶激活剂）也可使胰岛cAMP水平升高；无论是否与霍乱毒素结合，甲基黄嘌呤的作用都被葡萄糖增强了。异丁基甲基黄嘌呤（0.05-1.0 mM）或5 μg/ml霍乱毒素可增强胰岛素对20 mM葡萄糖的释放。然而，只有0.5 ~ 1.0 mM异丁基甲基黄嘌呤在3 mM葡萄糖存在下刺激胰岛素释放，而0.05 ~ 0.1 mM异丁基甲基黄嘌呤或5 μg/ml霍乱毒素在低葡萄糖浓度下对胰岛素分泌没有影响。这些camp促进和胰岛素释放活性之间的差异表明，葡萄糖不是通过激活β细胞腺苷酸环化酶来启动胰岛素释放的。葡萄糖通过在β细胞中代谢，既可以产生与cAMP不同的释放启动信号，又可以增强cAMP的形成，从而使启动信号的作用增强。
Insulin release and the content of cAMP were studied in microdissected pancreatic islets of noninbredob/ob(obese) mice. In the absence of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, 20 mM glucose had no effect on cAMP save a very small initial rise detectable by a freeze-stop perifusion technique only. However, combined with this methylxanthine, 20 mM glucose produced significant increases of cAMP both in perifused islets and in islets conventionally incubated in closed vials. Glucose shared this capacity to raise the cAMP level with D-glyceraldehyde and 1,3-dihydroxyacetone. Isobutylmethylxanthine (0.05-1.0 mM) or 5 μg/ml of cholera toxin, an activator of adenylate cyclase, also increased the islet cAMP level; the effects of the methylxanthine, whether or not combined with cholera toxin, were potentiated by glucose. Isobutylmethylxanthine (0.05-1.0 mM) or 5 μg/ml of cholera toxin potentiated insulin release in response to 20 mM glucose. However, only 0.5-1.0 mM isobutylmethylxanthine stimulated insulin release in the presence of 3 mM glucose, whereas 0.05-0.1 mM isobutylmethylxanthine or 5 μg/ml of cholera toxin had no effect on secretion at the low glucose concentration. These discrepancies between cAMP-promoting and insulin-releasing activities suggest that glucose does not initiate insulin release by activating the β-cell adenylate cyclase. By being metabolized in the β-cells, glucose may both create a release-initiating signal not identical with cAMP and enhance cAMP formation, leading to potentiation of the effect of the initiator signal.