A role for kisspeptin in islet function
A role for kisspeptin in islet function
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DOI：
10.1007/s00125-006-0343-z
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发表时间：
2006-09-01
期刊：
影响因子：
8.2
通讯作者：
Jones, P. M.
中科院分区：
文献类型：
--
作者：
Hauge-Evans, A. C.;Richardson, C. C.;Jones, P. M.
目的/假设我们研究了KISS1及其受体GPR54在胰岛中的表达，并探讨了外源性Kispeptin对胰岛素分泌的影响。方法采用RT-PCR和免疫组织化学方法检测KISS1和GPR54mRNAs在人和小鼠胰岛以及β(MIN6)和α-(α-TC1)细胞系中的表达。结果KISS1和Gpr54mRNAs在人和小鼠胰岛中均有表达，在MIN6和AlphaTC1内分泌细胞系中也有Gpr54mRNA的表达。在小鼠胰腺切片中，KISS1和Gpr54免疫反应阳性细胞共存于胰岛内的β细胞和α细胞，但在外分泌胰腺中未检测到。小鼠和人胰岛暴露于KISS_1可刺激葡萄糖诱导的胰岛素分泌(20 mmoL/L)，但对亚刺激浓度葡萄糖(2 mmoL/L)的基础胰岛素分泌速率无影响。相反，在2和20 mmol/L葡萄糖浓度下，KISS1均抑制MIN6细胞胰岛素分泌。结论首次报道Gpr54/KISS1系统在内分泌胰腺中表达，影响胰岛β细胞的分泌功能。这些观察结果表明，该系统在胰岛功能的正常调节中起着重要作用。
Aims/hypothesis We investigated the production of kisspeptin (KISS1) and the KISS1 receptor, GPR54, in pancreatic islets and determined the effects of exogenous kisspeptin on insulin secretion.Methods RT-PCR and immunohistochemistry were used to detect expression of KISS1 and GPR54 mRNAs and the production of KISS1 and GPR54 in human and mouse islets and in beta (MIN6) and alpha- (alphaTC1) cell lines. The effects of KISS1 on basal and glucose-induced insulin secretion from mouse and human islets were measured in a perifusion system.Results KISS1 and GPR54 mRNAs were both detected in human and mouse islets, and GPR54 mRNA expression was also found in the MIN6 and alphaTC1 endocrine cell lines. In sections of mouse pancreas, KISS1 and GPR54 immunoreactivities were co-localised in both beta and alpha cells within islets, but were not detected in the exocrine pancreas. Exposure of mouse and human islets to KISS1 caused a stimulation of glucose-induced (20 mmol/l) insulin secretion, but had no effect on the basal rate of secretion at a sub-stimulatory concentration of glucose (2 mmol/l). In contrast, KISS1 inhibited insulin secretion from MIN6 cells at both 2 and 20 mmol/l glucose. KISS1 had no significant effect on glucagon secretion from mouse islets.Conclusions/interpretation This is the first report to show that the GPR54/KISS1 system is expressed in the endocrine pancreas, where it influences beta cell secretory function. These observations suggest an important role for this system in the normal regulation of islet function.