title: Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect.
abstract: AMPK activation may stimulate glucose uptake in skeletal muscle, but the results in humans have so far been inconclusive. The authors investigated whether infusion of the AMPK activator, 5-aminoimidazole-4-carboxamide-riboside (AICAR), increased whole-body glucose infusion rate (GIR) and forearm skeletal muscle glucose uptake (FGU) during hyperin-sulinemia in vivo in healthy humans. Ten participants (paired data: n = 8) underwent 2 euglycemic hyperinsulinemic clamps (60 mU·m(-2)·min(-1), 120 minutes) with concomitant AICAR (67 mg·kg(-1)) or placebo (saline) administration over the last 60 minutes. The authors also measured forearm blood flow (FBF; plethysmography), heart rate, blood pressure, and AICAR and AICA-ribotide (ZMP) concentrations in plasma and erythrocytes. FGU and GIR (T = 95-120 min) did not differ between insulin + AICAR and insulin + placebo. Compared with insulin + placebo, insulin + AICAR raised heart rate more profoundly (T = 60-120 minutes: from 58 ± 3 to 70 ± 3 vs 60 ± 4 to 63 ± 4 bpm for placebo; P < .05 between treatments) and lowered blood pressure significantly. AICAR plasma concentrations increased significantly during AICAR infusion; AICAR was rapidly taken up by erythrocytes and phosphorylated to ZMP. In conclusion, AICAR does not seem to have a direct effect on systemic or local glucose uptake in humans. AICAR increases heart rate and decreases blood pressure, most likely by systemic vasodilation.
authors.affiliation: Department of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.bosselaar@aig.umcn.nl
authors.forename: Marlies
authors.initials: M
authors.lastname: Bosselaar
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Tack
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D012265:Ribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D001786:Blood Glucose; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose