Effects of Glucose on Insulin Release and on Intermediary Metabolism of Isolated Perifused Pancreatic Islets from Fed and Fasted Rats
Effects of Glucose on Insulin Release and on Intermediary Metabolism of Isolated Perifused Pancreatic Islets from Fed and Fasted Rats
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葡萄糖对进食和禁食大鼠离体灌注胰岛胰岛素释放和中间代谢的影响
DOI：
10.2337/diab.29.1.1
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发表时间：
1980
期刊：
影响因子：
7.7
通讯作者：
F. Matschinsky
中科院分区：
文献类型：
--
作者：
M. Trus;H. Warner;F. Matschinsky
我们研究了葡萄糖诱导的胰岛素释放与喂食和禁食大鼠胰岛中间代谢之间的关系。将分离的胰岛进行灌注，并在流出物中测量胰岛素释放量。在将胰岛从2.4 mM葡萄糖切换到8.6或14.5 mM葡萄糖或从2.4 mM葡萄糖切换到14.5 mM葡萄糖后的不同时间，将胰岛快速冷冻，冷冻干燥，随后使用酶荧光法分析葡萄糖-6- p，果糖-1,6- p2加三糖- p， P1， ATP， ADP, 5'-AMP， NADH， NADPH，总NAD和总NADP的组织含量。当喂食大鼠的胰岛暴露于高糖环境时，胰岛素释放增加，胰岛中葡萄糖-6- p、果糖-1,6- p2 +三糖- p、NADH和NADPH含量增加。刺激时P1和5′-AMP含量明显下降。总腺嘌呤核苷酸含量保持不变。当浸润液中加入1.5 mM P1时，也发生了类似的分泌和代谢变化。当葡萄糖刺激的胰岛切换回低糖状态10分钟后，除果糖-1,6- p2 +三糖- p、5′-AMP、NADPH和可能的ATP外，所有物质均恢复到刺激前水平。饥饿3天后，大鼠对8.6 mM葡萄糖的分泌反应被阻断。果糖-1,6- p2和三糖- p升高，但未达到喂养大鼠胰岛中存在的水平。（ATP）/（5′-AMP）和(ATP)/(P1,)（ADP）的比值升高至葡萄糖刺激大鼠胰岛观察值。高糖喂养大鼠胰岛的代谢变化与糖酵解的激活与胰岛素释放的刺激速率一致。尽管糖酵解的重要激活剂- p1和5′-AMP减少，但仍会发生这种情况。糖酵解的增强可能是由于果糖-6- p水平的增加激活了p -果糖激酶。在饥饿大鼠胰岛中，8.6 mM葡萄糖对糖酵解的激活作用不明显。尽管进食大鼠和禁食大鼠胰岛的分泌反应不同，但胰岛磷酸化状态的变化，特别是P1和5'-AMP水平的变化是相似的。
We examined the relationship between glucose-induced insulin release and the intermediary metabolism of islets from fed and fasted rats. Isolated islets were perifused and insulin release measured in the effluent. At various times after switching islets from 2.4 to 8.6 or 14.5 mM glucose or from 2.4 to 14.5 and back to 2.4 mM glucose, islets were quickly frozen, freeze dried, and subsequently analyzed for tissue content of glucose-6-P, fructose-1,6-P2 plus triose-P, P1, ATP, ADP, 5'-AMP, NADH, NADPH, total NAD, and total NADP using enzymatic fluorometric procedures. When islets from fed rats were exposed to high glucose, there were concomitant increases of insulin release and islet content of glucose-6-P, fructose-1,6-P2 plus triose-P, NADH, and NADPH. During stimulation P1 and 5'-AMP content fell markedly. The total adenine nucleotide content remained constant. Similar secretory and metabolic changes occurred when 1.5 mM P1 was added to the perifusion fluid. When glucose-stimulated islets were switched back to low glucose for 10 min, all substances but fructose-1,6-P2 plus triose-P, 5'-AMP, NADPH, and possibly ATP returned to the prestimulatory level. Starvation of rats for 3 days blocked the secretory response to 8.6 mM glucose. Fructose-1,6-P2 plus triose-P rose but it did not attain the level existing in islets from fed rats. The ratios (ATP)/(5'-AMP) and (ATP)/(P1,)(ADP) increased to the values observed in glucose-stimulated islets of fed rats. The metabolic changes in islets from fed rats exposed to high glucose are consistent with an activation of glycolysis occurring concomitantly with stimulated rates of insulin release. This occurs despite the decrease of important activators of glycolysis—P1 and 5'-AMP. The enhanced glycolysis possibly results from P-fructokinase activation by increased fructose-6-P levels. Activation of glycolysis with 8.6 mM glucose was not as pronounced in islets from starved rats. Despite the different secretory response of islets from fed and fasted rats, the changes of phosphorylation state in the islets, in particular, P1, and 5'-AMP levels, were similar.