AMP kinase-induced skeletal muscle glucose but not long-chain fatty acid uptake is dependent on nitric oxide.

Shearer J, Fueger PT, Vorndick B, Bracy DP, Rottman JN, Clanton JA, Wasserman DH
Diabetes. 2004 53 (6): 1429-35

PMID: 15161745 · DOI:10.2337/diabetes.53.6.1429

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 approximately 6.5 mmol/l in all groups, and an intravenous bolus of 2-deoxy[(3)H]glucose and [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid was administered to obtain indexes of glucose (K(g)) and LCFA (K(f)) uptake and clearance. At 150 min, soleus, gastrocnemius, and superficial vastus lateralis were excised for tracer determination. Both K(g) and K(f) increased with AICAR in all muscles studied. K(g) decreased with increasing muscle composition of type 1 slow-twitch fibers, whereas K(f) increased. In addition, AICAR-induced increases in K(g) but not K(f) 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.

MeSH Terms (23)

Adenylate Kinase Aminoimidazole Carboxamide Animals Blood Glucose Enzyme Activation Enzyme Inhibitors Fat Emulsions, Intravenous Fatty Acids Fatty Acids, Nonesterified Glucose Glucose Clamp Technique Immunoblotting Insulin Kinetics Male Muscle, Skeletal Muscle Fibers, Fast-Twitch Muscle Fibers, Slow-Twitch NG-Nitroarginine Methyl Ester Nitric Oxide Rats Rats, Sprague-Dawley Ribonucleotides

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