Diabetes 51:2703-2708, 2002
© 2002 by the American Diabetes Association, Inc.
Isoform-Specific Regulation of 5' AMP-Activated Protein Kinase in Skeletal Muscle From Obese Zucker (fa/fa) Rats in Response to Contraction
Brian R. Barnes1,
Jeffrey W. Ryder1,
Tatiana L. Steiler1,
Lee G.D. Fryer2,
David Carling2, and
Juleen R. Zierath1
1 Department of Clinical Physiology and Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
2 MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, U.K.
Glucose transport can be activated in skeletal muscle in response to insulin via activation of phosphoinositide (PI) 3-kinase and in response to contractions or hypoxia, presumably via activation of 5' AMP-activated protein kinase (AMPK). We determined the effects of insulin and muscle contraction/hypoxia on PI 3-kinase, AMPK, and glucose transport activity in epitrochlearis skeletal muscle from insulin-resistant Zucker (fa/ fa) rats. Insulin-stimulated glucose transport in isolated skeletal muscle was reduced 47% in obese versus lean rats, with a parallel 42% reduction in tyrosine-associated PI 3-kinase activity. Contraction and hypoxia elicited normal responses for glucose transport in skeletal muscle from insulin-resistant obese rats. Isoform-specific AMPK activity was measured in skeletal muscle in response to insulin, contraction, or hypoxia. Contraction increased AMPK 1 activity 2.3-fold in lean rats, whereas no effect was noted in obese rats. Hypoxia increased AMPK 1 activity to a similar extent (more than sixfold) in lean and obese rats. Regardless of genotype, contraction, and hypoxia, each increased AMPK 2 activity more than fivefold, whereas insulin did not alter either AMPK 1 or - 2 activity in skeletal muscle. In conclusion, obesity-related insulin resistance is associated with an isoform-specific impairment in AMPK 1 in response to contraction. However, this impairment does not appear to affect contraction-stimulated glucose transport. Activation of AMPK 2 in response to muscle contraction/ exercise is associated with a parallel and normal increase in glucose transport in insulin-resistant skeletal muscle.

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Copyright © 2002 by the American Diabetes Association.
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