Attenuation of insulin resistance by chronic beta(2)-adrenergic agonist treatment - Possible muscle specific contributions

A possible mechanism by which chronic clenbuterol treatment causes multiple physiological changes in skeletal muscle that leads to reduced insulin res istance in the obese Zucker rat (fa/fa) was investigated. Animals were gava ged with clenbuterol (CB) (0.8 mgkg(-1).day(-1)), terbutaline (TB) (1.0 mg. kg(-1).day(-1)), or control (CT) vehicle for six weeks. Oral glucose tolera nce and insulin responses were markedly improved in CB rats and impaired in TB rats. CB treatment caused a 24-34% gain in muscle mass in all muscle fi ber types, and increases in 3-O-methyglucose transport (2-fold) and GLUT4 c oncentration (57%) in fast twitch glycolytic (FG) muscle. Oxidative capacit y was reduced in both FG (47%) and fast twitch oxidative (FO) muscle (30%), but not in slow twitch oxidative (SO) muscle. Null model analysis for rece ptor occlusion demonstrated that most functional P-adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We propose that hype rtrophy is the result of continuous direct activation of beta -adrenoceptor s while loss in oxidative capacity may be the result of receptor down regul ation. Improvements in insulin resistance may have been due, in part, to bo th increases in lean body mass and specific adaptations in FG muscle. (C) 2 001 Elsevier Science Inc. All rights reserved.