Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom.
PLoS One. 2019 Jun 4;14(6):e0217925. doi: 10.1371/journal.pone.0217925. eCollection 2019.
There is an increasing amount of clinical evidence that hypomagnesemia (serum Mg2+ levels < 0.7 mmol/l) contributes to type 2 diabetes mellitus pathogenesis. Amongst other hypotheses, it has been suggested that Mg2+ deficiency affects insulin secretion. The aim of this study was, therefore, to investigate the acute effects of extracellular Mg2+ on glucose-stimulated insulin secretion in primary mouse islets of Langerhans and the rat insulinoma INS-1 cell line. Here we show that acute lowering of extracellular Mg2+ concentrations from 1.0 mM to 0.5 mM did not affect glucose-stimulated insulin secretion in islets or in insulin-secreting INS-1 cells. The expression of key genes in the insulin secretory pathway (e.g. Gck, Abcc8) was also unchanged in both experimental models. Knockdown of the most abundant Mg2+ channel Trpm7 by siRNAs in INS-1 cells resulted in a 3-fold increase in insulin secretion at stimulatory glucose conditions compared to mock-transfected cells. Our data suggest that insulin secretion is not affected by acute lowering of extracellular Mg2+ concentrations.
越来越多的临床证据表明,低镁血症(血清 Mg2+水平 < 0.7mmol/L)可导致 2 型糖尿病的发病机制。在其他假说中,有人认为镁缺乏会影响胰岛素分泌。因此,本研究旨在探讨细胞外镁对原代小鼠胰岛和大鼠胰岛素瘤 INS-1 细胞系葡萄糖刺激的胰岛素分泌的急性影响。在这里,我们发现将细胞外镁浓度从 1.0mM 急性降低至 0.5mM 不会影响胰岛或胰岛素分泌的 INS-1 细胞中的葡萄糖刺激的胰岛素分泌。在这两种实验模型中,胰岛素分泌途径中的关键基因(如 Gck、Abcc8)的表达也没有改变。用 siRNAs 敲低 INS-1 细胞中最丰富的镁通道 Trpm7,与 mock 转染细胞相比,在刺激葡萄糖条件下胰岛素分泌增加了 3 倍。我们的数据表明,急性降低细胞外镁浓度不会影响胰岛素分泌。