Abstract
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.
Highlights
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 [1]
To investigate whether Mg2+ fulfils a functional role in pancreatic β cells in a normal and hyperglycemic environment, acute effects of extracellular Mg2+ on insulin secretion were examined in primary mouse islets of Langerhans (Fig 1)
In islets cultured at 25 mM glucose, there was no difference in basal insulin secretion (2mM glucose) at low and normal Mg2+ (Fig 2C and 2D)
Summary
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 [1]. 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) [2]. Several epidemiological studies have shown that hypomagnesemia is higher in T2DM patients (14% - 48%) than in controls (2.5% - 15%) [3]. A patient cohort of almost 400 T2DM patients showed that 30.6% suffered from hypomagnesemia with plasma Mg2+ levels below 0.7 mmol/L [4]. Mg2+ supplementation in T2DM patients improved insulin sensitivity and glucose metabolism [5,6,7]
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