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

Abstract

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 (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.