Glucose uptake and GLUT-4 protein distribution in skeletal muscle of the obese Zucker rat. 1994

J T Brozinick, and G J Etgen, and B B Yaspelkis, and J L Ivy
Department of Kinesiology, University of Texas at Austin 78712.

The rates of muscle glucose uptake of lean and obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin), in the presence of a maximally stimulating concentration of insulin (10 mU/ml), and after muscle contraction elicited by electrical stimulation of the sciatic nerve. After perfusion, plasma and microsomal membranes were isolated from selected hindlimb muscles for determination of GLUT-4 protein distribution. Under basal conditions, rates of glucose uptake were similar for lean and obese rats despite plasma membranes from lean rats containing 82% more GLUT-4 protein than obese rats. Insulin stimulation resulted in significant increases in plasma membrane GLUT-4 protein concentration in lean but not obese rats. Glucose uptake of lean rats (35.3 +/- 4.7 mumol.h-1.g-1) in the presence of insulin was approximately fourfold greater than that of obese rats (8.8 +/- 1.3 mumol.h-1.g-1), but this difference in glucose uptake could not be completely accounted for by the difference in plasma membrane GLUT-4 protein concentration. Stimulation by contraction resulted in significant increases in plasma membrane GLUT-4 protein concentration in both lean and obese rats and similar rates of glucose uptake. These results suggest that the muscle insulin resistance of the obese Zucker rat is due to 1) a reduced plasma membrane GLUT-4 protein concentration, which results in part from an impairment in the insulin-stimulated GLUT-4 protein translocation process, and 2) a defect in the insulin-stimulated activation of this protein. However, contraction-stimulated glucose uptake, GLUT-4 protein translocation, and activation are normal in the obese Zucker rat.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D009004 Monosaccharide Transport Proteins A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES. Hexose Transport Proteins,Band 4.5 Preactin,Erythrocyte Band 4.5 Protein,Glucose Transport-Inducing Protein,Hexose Transporter,4.5 Preactin, Band,Glucose Transport Inducing Protein,Preactin, Band 4.5,Proteins, Monosaccharide Transport,Transport Proteins, Hexose,Transport Proteins, Monosaccharide,Transport-Inducing Protein, Glucose
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009124 Muscle Proteins The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN. Muscle Protein,Protein, Muscle,Proteins, Muscle
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009597 4-Nitrophenylphosphatase An enzyme that catalyzes the hydrolysis of nitrophenyl phosphates to nitrophenols. At acid pH it is probably ACID PHOSPHATASE (EC 3.1.3.2); at alkaline pH it is probably ALKALINE PHOSPHATASE (EC 3.1.3.1). EC 3.1.3.41. 4-Nitrophenyl Phosphatase,K+-NPPase,K-Dependent p-Nitrophenylphosphatase,K-p NPPase,Nitrophenyl Phosphatase,p-NPPase,p-Nitrophenylphosphatase,para-Nitrophenyl Phosphatase,para-Nitrophenylphosphatase,4 Nitrophenyl Phosphatase,4 Nitrophenylphosphatase,K Dependent p Nitrophenylphosphatase,K p NPPase,K+ NPPase,p NPPase,p Nitrophenylphosphatase,p-Nitrophenylphosphatase, K-Dependent,para Nitrophenyl Phosphatase,para Nitrophenylphosphatase
D009765 Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
D011188 Potassium An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011924 Rats, Zucker Two populations of Zucker rats have been cited in research--the "fatty" or obese and the lean. The "fatty" rat (Rattus norvegicus) appeared as a spontaneous mutant. The obese condition appears to be due to a single recessive gene. Zucker Rat,Zucker Rats,Rat, Zucker
D005260 Female Females

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