Alcohol consumption improves insulin signaling in the myocardium

Abstract

Background In a previous study, we demonstrated that swine with metabolic syndrome treated with alcohol had improved insulin signaling. We developed a follow-up study to evaluate the effects of alcohol on ischemic myocardium in animals without metabolic syndrome. Methods Fourteen Yorkshire swine underwent placement of an ameroid constrictor to induce chronic myocardial ischemia. Postoperatively, one group was supplemented with ethanol (ETOH), and one group was supplemented with sucrose (SUC) daily to normalize caloric intake.After 7 weeks, all animals underwent dextrose challenge and harvest of non-ischemic and ischemic myocardium. Tissues were analyzed for protein expression and histologic analysis. Results There was no difference in BMI, serum glucose or insulin levels. However ethanol supplementation up-regulated PI3K, pAKT, AKT and pFOX01 expression, which may promote insulin signaling and down regulated inhibitors of insulin signaling pIRS1 and pIRS2. There was no difference in intramyocardial glycogen, but there was increased GLUT4 expression in the ETOH group, which may promote glucose utilization. Conclusions Despite similar serum glucose and insulin levels, alcohol consumption up-regulates the insulin signaling pathway in the absence of metabolic syndrome in both nonischemic and chronically ischemic myocardium. These results suggest that alcohol selectively up-regulates the insulin signaling pathway despite normoglycemia.

Alcohol Consumption Mitigates Apoptosis and Mammalian Target of Rapamycin Signaling in Myocardium

“…Previous studies conducted by our group have demonstrated that alcohol supplementation improves insulin signaling and endothelial dysfunction and increases myocardial perfusion and angiogenesis. 3, 6, 7 Perhaps the improved insulin signaling optimizes cell energy utilization and the increased blood supply to the ischemic myocardium reduces the ischemic insult, resulting in an overall reduction in cell stress and cell death. Our group has also demonstrated that alcohol supplementation reduces oxidative stress in ischemic myocardium.…”

“…3–5 In another swine model of daily moderate alcohol consumption, we have shown that alcohol improves myocardial insulin signaling, myocardial perfusion, angiogenesis and endothelial dysfunction in chronically ischemic myocardium. 6, 7 …”

Alcoholic Cardiomyopathy: Disrupted Protein Balance and Impaired Cardiomyocyte Contractility

“…Next, in cardiomyocytes isolated from rats given alcohol for 22 weeks glucose transporter type 4 (GLUT4) mRNA and protein was significantly decreased in medium (2.5 g/kg/d) and high (5 g/kg/d) dosed animals but not in those receiving low dose (0.5 g/kg/d) alcohol (Chen et al., ). Contrary to this finding, moderate levels of daily alcohol consumption by male miniswine (90 ml, 50%/vol daily; 7 weeks) increased insulin myocardial signaling as evidence by increased GLUT4 membrane translocation (Elmadhun et al., , ). However, many other indices (i.e., phosphorylation of insulin receptor substrate [IRS]‐1 Ser612 and IRS2 Ser371, glycogen content and phosphorylation of glycogen synthase kinase‐3 β Ser9) remained unchanged (Elmadhun et al., ) indicating a discrepancy between pathway activation and outcome.…”

Alcohol and the Heart: A Proteomics Analysis of Pericardium and Myocardium in a Swine Model of Myocardial Ischemia

“…In a swine model of chronic myocardial ischemia and metabolic syndrome, we reported that animals supplemented with moderate doses of red wine (375 mL) or vodka (112 mL), (45 g ethanol/day) had improved endothelial function and myocardial perfusion, improved insulin signaling in peripheral tissues, reduced protein oxidative stress, and surprisingly reduced pericardial adhesions at reoperation [7][8][9][10][11]. In a subsequent swine study of chronic myocardial ischemia and moderate alcohol supplementation, we found that alcohol improved endothelial dysfunction, insulin signaling, and angiogenesis, and reduced myocardial apoptosis and pericardial adhesions at reoperation [7,12,13].…”