AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
Insulin-stimulated glucose uptake is increased in white but not red muscle of insulin-resistant high-fat-fed (HF) rats after administration of the AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). To investigate whether a lesser AICAR effect on glucose uptake in red muscle was offset by a greater effect on fatty acid (FA) uptake, we examined acute effects of AICAR on muscle glucose and FA fluxes in HF rats. HF rats received AICAR (250 mg/kg) subcutaneously. At 30 min, a mixture of either (3)H-(R)-2-bromopalmitate/(14)C-palmitate or (3)H-2-deoxyglucose/(14)C-glucose was administered intravenously to assess muscle FA and glucose uptake. AICAR decreased plasma levels of glucose (approximately 25%), insulin (approximately 60%), and FAs (approximately 30%) at various times over the next 46 min (P < 0.05 vs. controls). In white muscle, AICAR increased both FA (2.4-fold) and glucose uptake (4.9-fold), associated with increased glycogen synthesis (6-fold). These effects were not observed in red muscle. We conclude that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK. Therefore, a lesser effect of AICAR to alleviate muscle insulin resistance in red versus white muscle is not explained by a relatively greater effect on FA uptake in the red muscle.
Iglesias
Miguel A
MA
Garvan Institute of Medical Research, Sydney, Australia.
Furler
Stuart M
SM
Cooney
Gregory J
GJ
Kraegen
Edward W
EW
Ye
Ji-Ming
JM
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology*
D004041:Dietary Fats; D005227:Fatty Acids; D009097:Multienzyme Complexes; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D005947:Glucose