IA-2β, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion
IA-2β, but not IA-2, is induced by ghrelin and inhibits glucose-stimulated insulin secretion
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DOI：
10.1073/pnas.0502470102
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发表时间：
2006-01-24
影响因子：
11.1
通讯作者：
Nanjo, K
中科院分区：
文献类型：
--
作者：
Doi, A;Shono, T;Nanjo, K
Ghrelin是一种新发现的多肽，是生长激素促分泌素受体的内源性配体。它已被证明具有各种中枢和外周效应，包括GH分泌、食物摄入以及胃和心脏效应。Ghrelin和GHS受体也在胰岛中表达。我们已经确定了几个ghrelin诱导基因的PCR选择扣除方法，其中是1型糖尿病，IA-2 β的p细胞自身抗原。在小鼠脑、胰腺和胰岛素瘤细胞系（MINIS和β TC 3）中，给予生长素释放肽增加IA-2 β mRNA。然而，IA-2，另一种结构相关的β细胞自身抗原的表达，不诱导生长激素释放肽。在MIN 6胰岛素瘤细胞中，给予生长素释放肽或过表达IA-2 β，但不过表达IA-2，抑制葡萄糖刺激的胰岛素分泌，此外，通过RNA干扰技术抑制IA-2 β表达改善了生长素释放肽对葡萄糖刺激的胰岛素分泌的抑制作用。这些发现有力地表明，生长激素释放肽对葡萄糖刺激的胰岛素分泌的抑制作用至少部分是由于生长激素释放肽诱导的IA-2 β表达增加。我们的数据表明生长激素释放肽，IA-2 β，和葡萄糖刺激的胰岛素分泌之间的联系。
Ghrelin is a newly discovered peptide and an endogenous ligand for growth hormone (GH) secretagogue (GHS) receptor. It has been shown to possess various central and peripheral effects, including GH secretion, food intake, and gastric and cardiac effects. Ghrelin and the GHS receptor are expressed also in pancreatic islets. We have identified several ghrelin-induced genes by PCR-select subtraction methods, among which is a p-cell autoantigen for type 1 diabetes, IA-2 beta. Administration of ghrelin increased IA-2 beta mRNA in mouse brain, pancreas, and insulinoma cell lines (MINIS and beta TC3). However, the expression of IA-2, another structurally related beta-cell autoantigen, was not induced by ghrelin. Administration of ghrelin or overexpression of IA-2 beta, but not overexpression of IA-2, inhibited glucose-stimulated insulin secretion in MIN6 insulinoma cells and, moreover, inhibition of IA-2 beta expression by the RNA interference technique ameliorated ghrelin's inhibitory effects on glucose-stimulated insulin secretion. These findings strongly suggest that inhibitory effects of ghrelin on glucose-stimulated insulin secretion are at least partly due to increased expression of IA-2 beta induced by ghrelin. Our data demonstrate the link among ghrelin, IA-2 beta, and glucose-stimulated insulin secretion.