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

Publication date: 5 February 2018
Source:Molecular and Cellular Endocrinology, Volume 461
Author(s): Izela Bernal-Sore, Mario Navarro-Marquez, César Osorio-Fuentealba, Francisco Díaz-Castro, Andrea del Campo, Camila Donoso-Barraza, Omar Porras, Sergio Lavandero, Rodrigo Troncoso
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.PurposeTo determine the effects of mifepristone on insulin-stimulated glucose uptake on a model of L6 rat-derived skeletal muscle cells.ResultsMifepristone 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.ConclusionsMifepristone enhanced insulin-stimulated glucose uptake through a mechanism that involves a decrease in mitochondrial function and AMPK activation in skeletal muscle cells.



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