Signals related to glucose metabolism regulate islet amyloid polypeptide (IAPP) gene expression in human pancreatic islets

Signals related to glucose metabolism regulate islet amyloid polypeptide (IAPP) gene expression in human pancreatic islets
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DOI:
10.1016/s0167-0115(96)02109-x
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发表时间:
1997-01-29
影响因子:
--
通讯作者:
Novials, A
Novials, A
中科院分区:
其他
文献类型:
--
作者:
Gasa, R;Gomis, R;Novials, A

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在人胰岛中研究了葡萄糖刺激IAPP基因表达的细胞内途径。葡萄糖(16.7 mM),而不是甘露糖,导致IAPP mRNA水平增加2.3倍;这种作用被放线菌素D抑制。在存在不可代谢的6-脱氧葡萄糖(16.7 mM)的情况下,IAPP mRNA水平显著降低。甘露庚酮糖和维拉帕米都阻断葡萄糖诱导的IAPP基因刺激。胰岛素基因对葡萄糖的反应幅度较小(1.3倍);上述药物均未对胰岛素mRNA含量产生显着影响。衣霉素在低和高糖培养基中分别引起IAPP mRNA水平增加2.4倍和2.7倍;然而,它也不改变胰岛素mRNA。它对大鼠IAPP或胰岛素mRNA也没有影响。我们的结论是,IAPP基因的表达调控来自葡萄糖代谢的信号,细胞内钙离子可能参与了这一反应。IAPP和胰岛素基因在培养的人胰岛中也不共调节。(C)1997年Elsevier Science B.V.
Intracellular pathways involved in glucose stimulation of IAPP gene expression were studied in human pancreatic islets. Glucose (16.7 mM), but not mannose, caused a 2.3-fold increase in IAPP mRNA levels; this effect was inhibited by actinomycin D. In the presence of the non-metabolizable 6-deoxyglucose (16.7 mM) IAPP mRNA levels were markedly depleted. Both mannoheptulose and verapamil blocked glucose-induced stimulation of the IAPP gene. The magnitude of the insulin gene response to glucose was smaller (1.3-fold); none of the above-mentioned agents had significant effects on insulin mRNA content. Tunicamycin elicited a 2.4- and 2.7-fold increase in IAPP mRNA levels in the low and high glucose media, respectively; however, it did nor change insulin mRNA. It had no effect on rat IAPP or insulin mRNAs, either. We conclude that IAPP gene expression is regulated by signals derived from glucose metabolism and that intracellular calcium may be involved in this response. IAPP and insulin genes are nor co-regulated in cultured human pancreatic islets. (C) 1997 Elsevier Science B.V.