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 Ser⁴⁷³ phosphorylation in L6 myotubes. In addition, mifepristone reduced oxygen consumption and ATP levels and increased AMPK Thr¹⁷² 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 mitochondrial function and AMPK activation in skeletal muscle cells.

Keywords: AMPK; Insulin; L6 rat cells; Mifepristone; Mitochondria; RU486.