Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Saxon Academy of Sciences Leipzig, Leipzig, Germany.
J Pineal Res. 2018 Aug;65(1):e12480. doi: 10.1111/jpi.12480. Epub 2018 Mar 25.
Recent investigations of our group established that melatonin modulates hormone secretion of pancreatic islets via melatonin receptor types MT1 and MT2. Expression of MT1 and MT2 has been shown in mouse, rat, and human pancreatic islets as well as in the β-, α-, and δ-cell lines INS-1, αTC1.9, and QGP-1. In view of these earlier investigations, this study was performed to analyze in detail the distribution and density of melatonin receptors on the main islet cell types in human pancreatic tissue obtained from nondiabetic and type 2 diabetic patients. Immunohistochemical analysis established the presence of MT1 and MT2 in β-, α-, and δ-cells, but notably, with differences in receptor density. In general, the lowest MT1 and MT2 receptor density was measured in α-cells compared to the 2 other cell types. In type 2 diabetic islets, MT1 and MT2 receptor density was increased in δ-cells compared to normoglycemic controls. In human islets in batch culture of a nondiabetic donor, an increase of somatostatin secretion was observed under melatonin treatment while in islets of a type 2 diabetic donor, an inhibitory influence could be observed, especially in the presence of 5.5 mmol/L glucose. These data suggest the following: i) cell-type-specific density of MT1 and MT2 receptors in human pancreatic islets, which should be considered in context of the hormone secretion of islets, ii) the influence of diabetes on density of MT1 and MT2 as well as iii) the differential impact of melatonin on somatostatin secretion of nondiabetic and type 2 diabetic islets.
近期我们小组的研究发现，褪黑素通过褪黑素受体 1 型（MT1）和 2 型（MT2）来调节胰岛激素的分泌。在胰岛细胞以及β细胞系 INS-1、αTC1.9 和 QGP-1 中，均已证实了 MT1 和 MT2 的表达。鉴于这些早期的研究，本研究旨在详细分析从非糖尿病和 2 型糖尿病患者中获得的人胰腺组织中主要胰岛细胞类型上褪黑素受体的分布和密度。免疫组织化学分析确立了 MT1 和 MT2 存在于β、α 和 δ 细胞中，但值得注意的是，受体密度存在差异。一般来说，与其他两种细胞类型相比，α 细胞中 MT1 和 MT2 受体的密度最低。在 2 型糖尿病胰岛中，与正常血糖对照组相比，δ 细胞中 MT1 和 MT2 受体的密度增加。在非糖尿病供体的胰岛分批培养中，观察到褪黑素处理后生长抑素分泌增加，而在 2 型糖尿病供体的胰岛中，观察到抑制作用，尤其是在存在 5.5mmol/L 葡萄糖的情况下。这些数据表明：i）人胰腺胰岛中 MT1 和 MT2 受体的细胞类型特异性密度，这应在胰岛激素分泌的背景下加以考虑；ii）糖尿病对 MT1 和 MT2 密度的影响；iii）褪黑素对非糖尿病和 2 型糖尿病胰岛生长抑素分泌的差异影响。
