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Involvement of Intracellular pH in Vascular Insulin Resistance

[ Vol. 17 , Issue. 5 ]

Author(s):

Marco A. Ramírez*, Ana R. Beltrán, Jorge E. Araya, Marcelo Cornejo, Fernando Toledo, Gonzalo Fuentes and Luis Sobrevia*   Pages 440 - 446 ( 7 )

Abstract:


The maintenance of the pH homeostasis is maintained by several mechanisms including the efflux of protons (H+) via membrane transporters expressed in almost all mammalian cells. Along these membrane transporters the sodium/H+ exchangers (NHEs), mainly NHE isoform 1 (NHE1), plays a key role in this phenomenon. NHE1 is under modulation by several environmental conditions (e.g. hyperglycaemia, protein kinase C activity) as well as hormones, including insulin. NHE1 activation causes intracellular alkalization in human endothelial cells leading to activation of the endothelial Nitric Oxide Synthase (eNOS) to generate NO. Intracellular alkalization is a phenomenon that also results in upregulation of the glucose transporter GLUT4 in cells that are responsive to insulin. A reduction in the removal of the extracellular D-glucose is seen in states of insulin resistance, such as in diabetes mellitus and obesity. Since insulin is a potent activator of eNOS in human endothelium, therefore causing vasodilation, and its vascular effect is reduced in insulin resistance it is likely that a defective signal to activate NHE1 in insulin target cells is expected. This phenomenon results in lower redistribution and activation of GLUT4 leading to reduced uptake of D-glucose and hyperglycaemia. The general concept of a role for NHE1, and perhaps other NHEs isoforms, in insulin resistance in the human vasculature is proposed.

Keywords:

pH, insulin resistance, insulin, endothelium, diabetes, human, glucose.

Affiliation:

Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Laboratorio de Fisiologia Celular, Departamento Biomedico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1270300, Laboratorio de Fisiologia Celular, Departamento Biomedico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1270300, Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024, Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontifical Catholic University of Chile, Santiago 8330024

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