CYCLIC ADP-RIBOSE IN INSULIN-SECRETION FROM PANCREATIC BETA-CELLS
CYCLIC ADP-RIBOSE IN INSULIN-SECRETION FROM PANCREATIC BETA-CELLS
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DOI：
10.1126/science.8420005
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发表时间：
1993-01-15
期刊：
影响因子：
56.9
通讯作者：
OKAMOTO, H
中科院分区：
文献类型：
--
作者：
TAKASAWA, S;NATA, K;OKAMOTO, H
肌醇1，4，5-三磷酸（IP 3）被认为是细胞内钙动员的第二信使。然而，在胰岛微粒体的无细胞系统中，环腺苷二磷酸-核糖（cADP-核糖），烟酰胺腺嘌呤二核苷酸（NAD+）代谢产物，而不是IP 3，诱导钙释放。在毛地黄皂苷透化的胰岛中，cADP-核糖和钙，而不是IP 3，诱导胰岛素分泌。胰岛微粒体与高浓度葡萄糖孵育的完整胰岛提取物结合时释放钙。连续添加cADP-核糖抑制钙释放反应的提取物与高浓度的葡萄糖处理的胰岛。相反，反复添加胰岛提取物抑制钙释放响应，随后加入cADP-核糖。这些结果表明，cADP-核糖是钙从胰岛微粒体释放的介质，并可能在胰岛中通过葡萄糖刺激产生，作为内质网中钙动员的第二信使。
Inositol 1,4,5-trisphosphate (IP3) is thought to be a second messenger for intracellular calcium mobilization. However, in a cell-free system of islet microsomes, cyclic adenosine diphosphate-ribose (cADP-ribose), a nicotinamide adenine dinucleotide (NAD+) metabolite, but not IP3, induced calcium release. In digitonin-permeabilized islets, cADP-ribose and calcium, but not IP3, induced insulin secretion. Islet microsomes released calcium when combined with the extract from intact islets that had been incubated with high concentrations of glucose. Sequential additions of cADP-ribose inhibited the calcium release response to extracts from islets treated with high concentrations of glucose. Conversely, repeated additions of the islet extract inhibited the calcium release response to a subsequent addition of cADP-ribose. These results suggest that cADP-ribose is a mediator of calcium release from islet microsomes and may be generated in islets by glucose stimulation, serving as a second messenger for calcium mobilization in the endoplasmic reticulum.