Ramracheya Reshma D, Muller Dany S, Squires Paul E, Brereton Helen, Sugden David, Huang Guo Cai, Amiel Stephanie A, Jones Peter M, Persaud Shanta J
Beta Cell Development & Function Group, School of Biomedical & Health Sciences, King's College London, London, UK.
J Pineal Res. 2008 Apr;44(3):273-9. doi: 10.1111/j.1600-079X.2007.00523.x. Epub 2008 Jan 9.
Melatonin is known to inhibit insulin secretion from rodent beta-cells through interactions with cell-surface MT1 and/or MT2 receptors, but the function of this hormone in human islets of Langerhans is not known. In the current study, melatonin receptor expression by human islets was examined by reverse transcription-polymerase chain reaction (RT-PCR) and the effects of exogenous melatonin on intracellular calcium ([Ca2+]i) levels and islet hormone secretion were determined by single cell microfluorimetry and radioimmunoassay, respectively. RT-PCR amplifications indicated that human islets express mRNAs coding for MT1 and MT2 melatonin receptors, although MT2 mRNA expression was very low. Analysis of MT1 receptor mRNA expression at the single cell level indicated that it was expressed by human islet alpha-cells, but not by beta-cells. Exogenous melatonin stimulated increases in intracellular calcium ([Ca2+]i) in dissociated human islet cells, and stimulated glucagon secretion from perifused human islets. It also stimulated insulin secretion and this was most probably a consequence of glucagon acting in a paracrine fashion to stimulate beta-cells as the MT1 receptor was absent in beta-cells. Melatonin did not decrease 3', 5'-cyclic adenosine monophosphate (cyclic AMP) levels in human islets, but it inhibited cyclic AMP in the mouse insulinoma (MIN6) beta-cell line and it also inhibited glucose-stimulated insulin secretion from MIN6 cells. These data suggest that melatonin has direct stimulatory effects at human islet alpha-cells and that it stimulates insulin secretion as a consequence of elevated glucagon release. This study also indicates that the effects of melatonin are species-specific with primarily an inhibitory role in rodent beta-cells and a stimulatory effect in human islets.
已知褪黑素通过与细胞表面的MT1和/或MT2受体相互作用来抑制啮齿动物β细胞分泌胰岛素，但这种激素在人胰岛中的功能尚不清楚。在本研究中，通过逆转录聚合酶链反应（RT-PCR）检测了人胰岛中褪黑素受体的表达，并分别通过单细胞微荧光测定法和放射免疫测定法确定了外源性褪黑素对细胞内钙（[Ca2+]i）水平和胰岛激素分泌的影响。RT-PCR扩增表明，人胰岛表达编码MT1和MT2褪黑素受体的mRNA，尽管MT2 mRNA表达非常低。在单细胞水平上对MT1受体mRNA表达的分析表明，它由人胰岛α细胞表达，而不由β细胞表达。外源性褪黑素刺激解离的人胰岛细胞内钙（[Ca2+]i）增加，并刺激灌流的人胰岛分泌胰高血糖素。它还刺激胰岛素分泌，这很可能是由于胰高血糖素以旁分泌方式作用于刺激β细胞，因为β细胞中不存在MT1受体。褪黑素不会降低人胰岛中3',5'-环磷酸腺苷（环磷酸腺苷）水平，但它会抑制小鼠胰岛素瘤（MIN6）β细胞系中的环磷酸腺苷，并且还会抑制MIN6细胞中葡萄糖刺激的胰岛素分泌。这些数据表明，褪黑素对人胰岛α细胞有直接刺激作用，并且由于胰高血糖素释放增加而刺激胰岛素分泌。本研究还表明，褪黑素的作用具有物种特异性，在啮齿动物β细胞中主要起抑制作用，而在人胰岛中起刺激作用。
