Glucose regulation of islet amyloid polypeptide gene expression in rat pancreatic islets
Glucose regulation of islet amyloid polypeptide gene expression in rat pancreatic islets
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DOI：
10.1152/ajpendo.1997.272.4.e543
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发表时间：
1997-04-01
影响因子：
5.1
通讯作者：
Novials, A
中科院分区：
文献类型：
--
作者：
Gasa, R;Gomis, R;Novials, A
研究了葡萄糖调节胰岛淀粉样多肽（IAPP）基因表达的细胞内途径。IAPP mRNA水平在用16.7 mM葡萄糖培养的胰岛中是对照组（5.5 mM葡萄糖）的三倍。甘露糖和氨基酸而不是2-脱氧葡萄糖或6-脱氧葡萄糖模仿葡萄糖的作用。甘露庚酮糖（糖酵解抑制剂）、维拉帕米和二氮嗪（影响钙信号通路）消除了高糖和低糖之间胰岛IAPP mRNA含量的差异。在低葡萄糖，IAPP mRNA水平增加了1.9倍，在用毛喉素或二丁酰腺苷3 '，5'-环磷酸（DBcAMP），但没有与12-O-十四烷酰佛波醇13-乙酸酯处理的胰岛。在高糖培养的胰岛中胰岛素mRNA水平是对照组的1.6倍;需要葡萄糖代谢，而没有观察到cAMP或二氮嗪的影响。IAPP和胰岛素共分泌到培养基中。我们的结论是，葡萄糖调节LAPP mRNA丰度需要细胞内代谢的己糖和钙可以作为这种效果的介质，cAMP，但不蛋白激酶C可能参与这种调节。
Intracellular pathways by which glucose regulates islet amyloid polypeptide (IAPP) gene expression in pancreatic islets were studied. IAPP mRNA levels were threefold higher in islets cultured with 16.7 mM glucose compared with control (5.5 mM glucose). Mannose and amino acids but not 2-deoxyglucose or 6-deoxyglucose mimicked the effect of glucose. Mannoheptulose (a glycolysis inhibitor) and verapamil and diazoxide (which affect calcium signaling pathway) abolished the difference in islet IAPP mRNA content between high and low glucose. At low glucose, IAPP mRNA levels were increased 1.9-fold in islets treated with forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) but not with 12-O-tetradecanoylphorbol 13-acetate. Insulin mRNA levels were 1.6-fold higher in islets cultured at high glucose than controls; glucose metabolism was required, whereas no effects of cAMP or diazoxide were observed. IAPP and insulin were cosecreted into the media. We conclude that glucose regulation of LAPP mRNA abundance requires intracellular metabolism of the hexose and that calcium may serve as a mediator of this effect; cAMP but not protein kinase C possibly participates in this regulation.