Chronic ethanol exposure alters expression of insulin-induced mitogen-activated protein kinases in hypertensive vascular smooth muscle cells
Insulin resistance is an important risk factor in development of cardiovascular diseases such as hypertension and atherosclerosis. However, the specific role of insulin resistance in the etiology of these diseases is poorly understood. On the other hand, ethanol is a potent vasoconstrictor which induces changes in mitogen activated protein kinases. We hypothesize that in hypertensive vascular smooth muscle cells (VSMCs), ethanol (ETOH) interferes with insulin action by altering mitogen activated protein kinases, the major signaling molecules implicated in the biological actions of insulin. By stimulating hypertensive (SHR) cells with 1–16 µM of insulin, ERK 1 & 2 expression increased in a time dependent manner with maximum expression occurring at 10 minutes, whereas, in normal cells (WKY), no significant increase in expression of ERK 1 & 2 was observed for at least 20 minutes. We measured expression of AKT under similar conditions. By contrast, in hypertensive cells, insulin inhibited AKT expression within the first 5 minutes. This observed insulin-induced inhibition of AKT was not observed at 10, 20, and 40 min of stimulation. On the contrary, exposing hypertensive cells chronically (24 hr) to elevated concentrations (50–800 mM) of ethanol prior to stimulating with insulin, ERK 1 & 2 expression decreased in a biphasic manner with 100 and 400 mM. Eight hundred micromoles of ethanol had maximum effect. Similarly, insulin-induced AKT decreased in hypertensive cells with maximum ETOH concentrations of 400 and 800 mM. From these data, we conclude that chronic ETOH negatively alters insulin signaling in hypertensive vascular smooth muscle cells providing an alternative molecular mechanism that may increase the risk of insulin resistance. This increased risk of insulin resistance may increase the possibility of cardiovascular diseases. ^
Sparkle D Williams,
"Chronic ethanol exposure alters expression of insulin-induced mitogen-activated protein kinases in hypertensive vascular smooth muscle cells"
ETD Collection for Tennessee State University.