Date Published: June 4, 2019
Publisher: Public Library of Science
Author(s): Lisanne M. M. Gommers, Thomas G. Hill, Frances M. Ashcroft, Jeroen H. F. de Baaij, Amar Abderrahmani.
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.
Globally, the number of people that suffer from type-2 diabetes mellitus (T2DM) is steadily increasing, and the prevalence is predicted to pass the threshold of 500 million people by 2030 . T2DM is characterized by impaired insulin secretion (i.e. insulin deficiency) and insulin sensitivity (i.e. insulin resistance), explaining the underlying pathophysiological mechanism for hyperglycemia (fasting serum blood glucose > 7 mmol/L) .
This study demonstrates that reduced extracellular Mg2+ does not impair insulin secretion from pancreatic β-cells. This conclusion is based on the following results: i) Acute exposure to low extracellular Mg2+ has no effect on insulin secretion from either isolated mouse islets of Langerhans or INS-1 cells; ii) In islets cultured at 25 mM glucose, to mimic the hyperglycemic state found in T2DM, insulin secretion was actually enhanced by reducing extracellular Mg2+; iii) The mRNA expression levels of Mg2+ channels/transporters and key players in GSIS, in both islets and INS1 cells, were unaffected by extracellular Mg2+.