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Diabetes 53:1429-1435, 2004
© 2004 by the American Diabetes Association, Inc.

AMP Kinase-Induced Skeletal Muscle Glucose But Not Long-Chain Fatty Acid Uptake Is Dependent on Nitric Oxide

Jane Shearer1, Patrick T. Fueger1, Brittney Vorndick1, Deanna P. Bracy1, Jeffery N. Rottman2, Jeffery A. Clanton3, and David H. Wasserman1,4

1 Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee
2 Department of Cardiology, Vanderbilt University School of Medicine, Nashville, Tennessee
3 Department of Radiology & Radiological Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee
4 Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee

The purpose of this study was to examine the effects of AMP kinase (AMPK) activation on in vivo glucose and long-chain fatty acid (LCFA) uptake in skeletal muscle and to examine the nitric oxide (NO) dependence of any putative effects. Catheters were chronically implanted in the carotid artery and jugular vein of male Sprague-Dawley rats. After 4 days of recovery, rats were given either water or water containing 1 mg/ml nitro-L-arginine methylester (L-NAME) for 2.5 days. After an overnight fast, rats underwent one of five protocols: saline, 5-aminoimidazole-4-carboxamide-1-B-D-ribofuranoside (AICAR) (10 mg · kg–1 · min–1), L-NAME, AICAR + L-NAME, or AICAR + Intralipid (20%, 0.02 ml · kg–1 · min–1). Glucose was clamped at ~6.5 mmol/l in all groups, and an intravenous bolus of 2-deoxy[3H]glucose and [125I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid was administered to obtain indexes of glucose (Kg) and LCFA (Kf) uptake and clearance. At 150 min, soleus, gastrocnemius, and superficial vastus lateralis were excised for tracer determination. Both Kg and Kf increased with AICAR in all muscles studied. Kg decreased with increasing muscle composition of type 1 slow-twitch fibers, whereas Kf increased. In addition, AICAR-induced increases in Kg but not Kf were abolished by L-NAME in the majority of muscles examined. This shows that the mechanisms by which AMPK stimulates glucose and LCFA uptake are distinct.

Address correspondence and reprint requests to Jane Shearer, Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University, Nashville, TN, 37232-0615. E-mail: jane.shearer{at}vanderbilt.edu


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