BACKGROUND: The mechanism by which chronic alcohol consumption impairs insulin sensitivity is unclear. We investigated the role of the Gs alpha-mediated pathway in decreasing insulin sensitivity in skeletal muscle after ethanol consumption. METHODS: Sixty male Wistar rats, divided into four groups, received either distilled water (controls; group I) or ethanol, which was administered by a gastric tube as a single daily dose of 5 g/kg (group II), 2.5 g/kg (group III), or 0.5 g/kg (group IV). After 20 weeks, fasting plasma glucose and serum insulin levels were measured. The hyperinsulinemic-euglycemic clamp study was performed under anesthesia to estimate whole-body insulin sensitivity. Insulin-stimulated glucose uptake was measured in vitro in dissected gastrocnemius muscle. Expression of glut4, Gs alpha, and Gi alpha was quantified using real-time PCR analysis and western blotting. cAMP levels were measured by ELISA. RESULTS: Compared with controls, the following observations were made: (1) the hyperinsulinemic-euglycemic clamp study revealed impaired insulin action at the whole-body level after ethanol treatment; (2) chronic ethanol feeding at 5 g/kg and 2.5 g/kg significantly decreased both basal and insulin-stimulated glucose uptakes in isolated skeletal muscle (p<0.05), which was accompanied by decreased expression of glut4 (p<0.05); (3) Gs alpha (mRNA and protein) expression in skeletal muscle was significantly increased in all three ethanol groups (p<0.05), and cAMP levels were also increased by ethanol treatment (p<0.05); and (4) there was no significant change in Gi alpha expression in all three ethanol groups. CONCLUSIONS: Chronic ethanol exposure decreased insulin-induced glucose uptake in rat skeletal muscle, which was associated with increased expression of Gs alpha. Because Gs alpha is a negative regulator of insulin sensitivity, the alteration in Gs alpha expression may contribute to the ethanol-induced impairment of insulin signal transduction.
BACKGROUND: The mechanism by which chronic alcohol consumption impairs insulin sensitivity is unclear. We investigated the role of the Gs alpha-mediated pathway in decreasing insulin sensitivity in skeletal muscle after ethanol consumption. METHODS: Sixty male Wistar rats, divided into four groups, received either distilled water (controls; group I) or ethanol, which was administered by a gastric tube as a single daily dose of 5 g/kg (group II), 2.5 g/kg (group III), or 0.5 g/kg (group IV). After 20 weeks, fasting plasma glucose and serum insulin levels were measured. The hyperinsulinemic-euglycemic clamp study was performed under anesthesia to estimate whole-body insulin sensitivity. Insulin-stimulated glucose uptake was measured in vitro in dissected gastrocnemius muscle. Expression of glut4, Gs alpha, and Gi alpha was quantified using real-time PCR analysis and western blotting. cAMP levels were measured by ELISA. RESULTS: Compared with controls, the following observations were made: (1) the hyperinsulinemic-euglycemic clamp study revealed impaired insulin action at the whole-body level after ethanol treatment; (2) chronic ethanol feeding at 5 g/kg and 2.5 g/kg significantly decreased both basal and insulin-stimulated glucose uptakes in isolated skeletal muscle (p<0.05), which was accompanied by decreased expression of glut4 (p<0.05); (3) Gs alpha (mRNA and protein) expression in skeletal muscle was significantly increased in all three ethanol groups (p<0.05), and cAMP levels were also increased by ethanol treatment (p<0.05); and (4) there was no significant change in Gi alpha expression in all three ethanol groups. CONCLUSIONS: Chronic ethanol exposure decreased insulin-induced glucose uptake in rat skeletal muscle, which was associated with increased expression of Gs alpha. Because Gs alpha is a negative regulator of insulin sensitivity, the alteration in Gs alpha expression may contribute to the ethanol-induced impairment of insulin signal transduction.
Authors: Stephen M Ford; Liz Simon; Curtis Vande Stouwe; Tim Allerton; Donald E Mercante; Lauri O Byerley; Jason P Dufour; Gregory J Bagby; Steve Nelson; Patricia E Molina Journal: Am J Physiol Regul Integr Comp Physiol Date: 2016-09-07 Impact factor: 3.619