Globally, over 400 million people suffer from type 2 diabetes mellitus (T2DM) and the prevalence is predicted to rise rapidly over the next decade. It has long been recognized that diabetes mellitus is associated with decreased plasma Mg2+ levels (plasma Mg2+ <0.7 mmol/L), which we recently investigated by showing low plasma Mg2+ levels in 30% of the patients with T2DM.
Hypomagnesemia is relevant as it increases progression from prediabetes to overt diabetes and associated with insulin resistance. Moreover, some studies have shown that oral Mg2+ supplementation may reduce progression towards diabetes and improve insulin sensitivity and the blood lipid profile. These findings and the strong association of plasma triglycerides with plasma Mg2+ levels, suggest that Mg2+ homeostasis and lipid metabolism are closely related.
Recently, we identified the first genetic link between fat metabolism and Mg2+ homeostasis. In a genome-wide association studies the ARL15 locus was associated with urinary Mg2+ levels, adiponectin levels, HDL and T2DM. Interestingly, in our study the ARL15 locus modified the association between Mg2+ and insulin resistance, suggesting that ARL15 contributes to the beneficial effects of Mg2+ in T2DM.
In this PhD project we aim to investigate role of low Mg2+ levels in lipid metabolism. The project ranges from molecule-to-man and includes the elucidation of the molecular function of ARL15, as well as, testing Mg2+ supplementation in human intervention studies. You will be employed by the Department of Physiology of the Radboudumc, Nijmegen. The project is funded by the Dutch Diabetes Research Foundation and will be executed in close collaboration with the department of Internal Medicine.
The salary will be in scale 10 or scale 10A Cao umc depending on education. Scale 10A: max € 40814 gross per year at full employment (incl. vacation bonus and end of year payments) or scale 10: max € 44687 gross per year at full employment (incl. vacation bonus and end of year payments).
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The department of Physiology provides an international and stimulating working environment for its 50 employees and is an exciting place to perform basic research, translational and clinical medicine, and enjoy teaching. The department encompasses complementary research groups whose interests range from cardiovascular disease, molecular regulation of ion transport processes in the kidney to the study of metabolism in the body. Working collaboratively within the department, we use our expertise to investigate how molecules, cells, organisms and humans function and how we might modulate their physiology to ultimately improve health in the patient.
This project will be executed in the Ion Transport group and is part of the Renal Theme within Radboud Institute for Molecular Life Sciences (RIMLS), a leading multidisciplinary graduate school within the domain of molecular mechanisms of disease and particularly in the fields of molecular medicine, cell biology and translational research.