Mifepristone enhances insulin stimulated Akt phosphorylation and glucose uptake in skeletal muscle cells

Abstract

Mifepristone is the only FDA-approved drug for glycaemia control in patients with Cushing's syndrome and type 2 diabetes. Mifepristone also has beneficial effects in animal models of diabetes and patients with antipsychotic treatment-induced obesity. However, the mechanisms through which Mifepristone produces its beneficial effects are not completely elucidated.

Purpose: To determine the effects of mifepristone on insulin-stimulated glucose uptake on a model of L6 rat-derived skeletal muscle cells.

Results: Mifepristone enhanced insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane and Akt Ser(473) phosphorylation in L6 myotubes. In addition, mifepristone reduced oxygen consumption and ATP levels and increased AMPIC Thr(172) phosphorylation. The knockdown of AMPK prevented the effects of mifepristone on insulin response.

Conclusions: Mifepristone enhanced insulin-stimulated glucose uptake through a mechanism that involves a decrease in mitochondria! function and AMPK activation in skeletal muscle cells.