Alteration of Major Insulin Signaling Molecules by Chronic Ethanol in Hypertensive Vascular Smooth Muscle Cells of Rats

摘要

Insulin resistance is an important risk factor in the development of cardiovascular diseases such as hypertension and atherosclerosis. However, despite its importance, the specific role of insulin resistance in the etiology of these diseases is poorly understood. At the same time, ethanol (ETOH) is a potent vasoconstrictor that primarily induces down regulation of mitogen activated protein kinases (MAPKs) which could exacerbate insulin resistance and possibly lead to cardiovascular diseases. This article describes how chronic ETOH exposure interferes with insulin signaling in hypertensive vascular smooth muscle cells (HVSMCs) which leads to the alteration of MAPKs, the major signaling molecules. Elevated (50 - 800 mM) chronic exposure (24 hr) of HVSMCS to ETOH prior to insulin stimulation decreased insulin-induced ERK 1/2 (MAPKs) and AKT expression. Similar experiments were conducted using normotensive cells from rat. These cells showed reductions in insulin-induced ERK 1/2 phosphorylation as well, but only at higher concentrations of ETOH (400 - 800 mM). These alterations in insulin signaling could provide an alternative molecular mechanism that may increase the risk of insulin resistance, thus increasing the possibility of cardiovascular diseases.