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Diabetes 50:1149-1157, 2001
© 2001 by the American Diabetes Association, Inc.

Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid

Improved Glucose Tolerance, Skeletal Muscle Insulin Action, and UCP-2 Gene Expression

J.W. Ryder1, C.P. Portocarrero2, X.M. Song1, L. Cui3, M. Yu1, T. Combatsiaris3, D. Galuska1, D.E. Bauman4, D.M. Barbano5, M.J. Charron3, J.R. Zierath1, and K.L. Houseknecht2

1 Department of Clinical Physiology, Karolinska Institute, Stockholm Sweden
2 Department of Animal Sciences, Purdue University, West Lafayette, Indiana
3 Department of Biochemistry, Yeshiva University, Bronx; and the Departments of
4 Animal Science and
5 Food Science, Cornell University, Ithaca, New York

Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferator–activated receptor (PPAR)-{gamma} response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-{gamma} mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake.



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