INOSINE-STIMULATED INSULIN RELEASE AND METABOLISM OF INOSINE IN ISOLATED MOUSE PANCREATIC-ISLETS
INOSINE-STIMULATED INSULIN RELEASE AND METABOLISM OF INOSINE IN ISOLATED MOUSE PANCREATIC-ISLETS
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DOI：
10.1042/bj1580335
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发表时间：
1976-01-01
影响因子：
4.1
通讯作者：
HEDESKOV, CJ
中科院分区：
文献类型：
--
作者：
CAPITO, K;HEDESKOV, CJ
肌苷是从分离的小鼠胰岛分泌胰岛素的有效的主要刺激物。肌苷诱导的胰岛素分泌在饥饿过程中被完全抑制，但通过向培养基中加入5 mM咖啡因完全恢复，通过加入5 mM葡萄糖部分恢复。甘露庚酮糖（3 mg/ml）增强了10 mM-肌苷在来自喂养小鼠的胰岛中的作用。进一步研究了肌苷刺激作用的机制，并且胰岛含有能够将肌苷转化为次黄嘌呤和核糖1-磷酸的核苷磷酸化酶。10 mM的肌苷可增加喂养小鼠胰岛中乳酸的产生和ATP、G-6-P（果糖1，6-二磷酸+丙糖磷酸）和环AMP [cAMP]的含量。在饥饿小鼠胰岛中，肌苷诱导的乳酸产生减少，cAMP浓度无变化，而ATP和G-6-P浓度升高。肌苷（10 mM）在来自饥饿小鼠的胰岛中诱导的（果糖1，6-二磷酸+丙糖磷酸）浓度高于来自进食小鼠的胰岛中的浓度，这表明在饥饿中，甘油醛3-磷酸脱氢酶或糖酵解中低于该步骤的其它酶的活性降低。肌苷生成葡萄糖的量可忽略不计。肌苷对胰岛匀浆中腺苷酸环化酶活性无直接影响。所观察到的胰岛素分泌和胰岛代谢的变化模拟了当葡萄糖和甘油醛刺激胰岛素分泌时所观察到的变化，并且由于既不是核糖也不是次黄嘌呤刺激的胰岛素释放，因此结果被解释为支持葡萄糖诱导的胰岛素分泌的底物位点假说，根据该假说，葡萄糖必须在β-葡萄糖受体中代谢。细胞开始分泌之前。
Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, G-6-P (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP [cAMP] in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cAMP could be demonstrated, whereas the concentration of ATP and G-6-P rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substratesite hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the .beta.-cells before secretion is initiated.