Attenuation of insulin resistance by chronic beta2-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 resistance in the obese Zucker rat (falfa) was investigated. Animals were gavaged with clenbuterol (CB) (0.8 mg x kg(-1) day(-1)), terbutaline (TB) (1.0 mg x kg(-1)day(-1)), or control (CT) vehicle for six weeks. Oral glucose tolerance 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 fiber types, and increases in 3-O-methyglucose transport (2-fold) and GLUT4 concentration (57%) in fast twitch glycolytic (FG) muscle. Oxidative capacity 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 receptor occlusion demonstrated that most functional beta-adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We propose that hypertrophy is the result of continuous direct activation of beta-adrenoceptors while loss in oxidative capacity may be the result of receptor down regulation. Improvements in insulin resistance may have been due, in part, to both increases in lean body mass and specific adaptations in FG muscle.
Castle
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Department of Kinesiology and Health Education, The University of Texas, Austin 78712, USA.
Yaspelkis
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BB
Kuo
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Ivy
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JL
D019325:3-O-Methylglucose / Q000378:metabolism; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D007333:Insulin Resistance / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018343:Receptors, Adrenergic, beta-2; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D005947:Glucose; D002976:Clenbuterol