Izela Bernal-Sore1, Mario Navarro-Marquez2, César Osorio-Fuentealba3, Francisco Díaz-Castro1, Andrea Del Campo4, Camila Donoso-Barraza1, Omar Porras5, Sergio Lavandero6, Rodrigo Troncoso7. 1. Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile. 2. Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. 3. Departamento de Kinesiología, Universidad Metropolitana de Ciencias de la Educación, Ñuñoa, Santiago, Chile; Centro de Investigación y Estudio del Consumo de Alcohol en Adolescentes (CIAA), Santiago, Chile. 4. Escuela de Química y Farmacia, Facultad de Ingeniería, Ciencia y Tecnología, Universidad Bernando O'Higgins, Santiago, Chile. 5. Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile; Centro de Investigación en Alimentos para el Bienestar en el Ciclo Vital (ABCvital), Universidad de Chile, Chile. 6. Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, USA. 7. Instituto de Nutrición y Tecnología de los Alimentos (INTA), Universidad de Chile, Santiago, Chile; Advanced Center for Chronic Disease (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Facultad de Medicina, Universidad de Chile, Santiago, Chile; Centro de Investigación en Alimentos para el Bienestar en el Ciclo Vital (ABCvital), Universidad de Chile, Chile. Electronic address: rtroncoso@inta.uchile.cl.
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.
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 AktSer473 phosphorylation in L6 myotubes. In addition, mifepristone reduced oxygen consumption and ATP levels and increased AMPKThr172 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.
Authors: Claudia Sepúlveda-Quiñenao; Juan M Rodriguez; Francisco Díaz-Castro; Andrea Del Campo; Roberto Bravo-Sagua; Rodrigo Troncoso Journal: Int J Mol Sci Date: 2022-05-17 Impact factor: 6.208
Authors: Gary N Landis; Tyler A U Hilsabeck; Hans S Bell; Tal Ronnen-Oron; Lu Wang; Devon V Doherty; Felicia I Tejawinata; Katherine Erickson; William Vu; Daniel E L Promislow; Pankaj Kapahi; John Tower Journal: Front Genet Date: 2021-09-24 Impact factor: 4.599
Authors: Andrea Del Campo; Catalina Salamanca; Angelo Fajardo; Francisco Díaz-Castro; Catalina Bustos; Camila Calfío; Rodrigo Troncoso; Edgar R Pastene-Navarrete; Claudio Acuna-Castillo; Luis A Milla; Carlos A Villarroel; Francisco A Cubillos; Mario Aranda; Leonel E Rojo Journal: Molecules Date: 2021-10-12 Impact factor: 4.411
Authors: Gary N Landis; Luke Riggan; Hans S Bell; William Vu; Tianyi Wang; Ina Wang; Felicia I Tejawinata; Sebastian Ko; John Tower Journal: Front Aging Date: 2022-07-22