Capito K, Hedeskov C J
Biochem J. 1976 Aug 15;158(2):335-40. doi: 10.1042/bj1580335.
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 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that 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, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate 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 substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated.
肌苷是分离的小鼠胰岛胰岛素分泌的一种强效主要刺激物。饥饿期间，肌苷诱导的胰岛素分泌完全受到抑制，但向培养基中添加5 mM咖啡因可使其完全恢复，添加5 mM葡萄糖可使其部分恢复。甘露庚酮糖（3 mg/ml）增强了喂食小鼠胰岛中10 mM肌苷的作用。进一步研究了肌苷刺激作用的机制，结果表明胰岛含有一种核苷磷酸化酶，能够将肌苷转化为次黄嘌呤和1-磷酸核糖。10 mM浓度的肌苷可增加喂食小鼠胰岛中的乳酸生成以及ATP、6-磷酸葡萄糖（1,6-二磷酸果糖+磷酸丙糖）和环磷酸腺苷的含量。在饥饿小鼠的胰岛中，肌苷诱导的乳酸生成减少，环磷酸腺苷浓度无变化，而ATP和6-磷酸葡萄糖浓度升高。10 mM肌苷在饥饿小鼠胰岛中诱导的（1,6-二磷酸果糖+磷酸丙糖）浓度高于喂食小鼠胰岛，这表明饥饿时3-磷酸甘油醛脱氢酶或糖酵解中此步骤以下其他酶的活性降低。由肌苷生成葡萄糖的量可忽略不计。肌苷对胰岛匀浆中的腺苷酸环化酶活性无直接影响。观察到的胰岛素分泌和胰岛代谢变化与葡萄糖和甘油醛刺激胰岛素分泌时的情况相似，且由于核糖和次黄嘌呤均未刺激胰岛素释放，这些结果被解释为支持葡萄糖诱导胰岛素分泌的底物位点假说，即葡萄糖在β细胞中必须先进行代谢才能启动分泌。
