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Ethanol Feeding Impairs Insulin‐Stimulated Glucose Uptake in Isolated Rat Skeletal Muscle: Role of Gs α and cAMP
Author(s) -
Wan Qiang,
Liu Yi,
Guan Qingbo,
Gao Ling,
Lee Kok Onn,
Zhao Jiajun
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000174768.78427.f6
Subject(s) - medicine , endocrinology , glut4 , skeletal muscle , insulin , basal (medicine) , glucose uptake , glucose transporter , ethanol , chemistry , insulin resistance , biology , biochemistry
Background: The mechanism by which chronic alcohol consumption impairs insulin sensitivity is unclear. We investigated the role of the Gs α–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 α, and Gi α 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 α (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 α 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 α. Because Gs α is a negative regulator of insulin sensitivity, the alteration in Gs α expression may contribute to the ethanol‐induced impairment of insulin signal transduction.