AMP kinase-induced skeletal muscle glucose but not long-chain fatty acid uptake is dependent on nitric oxide.
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.
Shearer
Jane
J
Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University, Nashville, TN, 37232-0615, USA. jane.shearer@vanderbilt.edu
Fueger
Patrick T
PT
Vorndick
Brittney
B
Bracy
Deanna P
DP
Rottman
Jeffery N
JN
Clanton
Jeffery A
JA
Wasserman
David H
DH
D000263:Adenylate Kinase / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D015151:Immunoblotting; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012265:Ribonucleotides; D009569:Nitric Oxide; D000620:Aminoimidazole Carboxamide; D000263:Adenylate Kinase; C031143:AICA ribonucleotide; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester