The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes
J. Gustavo Vazquez-Jimenez,
M. Stephanie Corpus-Navarro,
J. Miguel Rodriguez-Chavez,
Hiram J. Jaramillo-Ramirez,
Judith Hernandez-Aranda,
Octavio Galindo-Hernandez,
J. Rene Machado-Contreras,
Marina Trejo-Trejo,
Agustin Guerrero-Hernandez,
J. Alberto Olivares-Reyes
Affiliations
J. Gustavo Vazquez-Jimenez
Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico City 07360, Mexico
M. Stephanie Corpus-Navarro
Laboratory of Molecular Pathogenesis, School of Medicine, Campus Mexicali, Autonomous University of Baja California, Mexicali, Baja California 21000, Mexico
J. Miguel Rodriguez-Chavez
Laboratory of Molecular Pathogenesis, School of Medicine, Campus Mexicali, Autonomous University of Baja California, Mexicali, Baja California 21000, Mexico
Hiram J. Jaramillo-Ramirez
Department of Internal Medicine, General Hospital of Mexicali, Mexicali, Baja California 21000, Mexico
Judith Hernandez-Aranda
Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico City 07360, Mexico
Octavio Galindo-Hernandez
Laboratory of Biochemistry, School of Medicine, Campus Mexicali, Autonomous University of Baja California, Mexicali, Baja California 21000, Mexico
J. Rene Machado-Contreras
Laboratory of Molecular Pathogenesis, School of Medicine, Campus Mexicali, Autonomous University of Baja California, Mexicali, Baja California 21000, Mexico
Marina Trejo-Trejo
School of Sports, Campus Mexicali, Autonomous University of Baja California, Mexicali, Baja California 21000, Mexico
Agustin Guerrero-Hernandez
Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico City 07360, Mexico
J. Alberto Olivares-Reyes
Department of Biochemistry, Center for Research and Advanced Studies of the National Polytechnic Institute, CINVESTAV-IPN, Mexico City 07360, Mexico
Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.
