Involvement of intracellular pH in vascular insulin resistance.

Involvement of intracellular pH in vascular insulin resistance. Curr Vasc Pharmacol. 2018 Sep 10;: Authors: Ramirez MA, Beltran AR, Araya JE, Cornejo M, Toledo F, Fuentes G, Sobrevia L 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 (v.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...
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research