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J Clin Pharmacol. 2011 Oct;51(10):1449-58. doi: 10.1177/0091270010382912. Epub 2010 Dec 8.

Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect.

Author information

1
Department of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.bosselaar@aig.umcn.nl

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.

PMID:
21148051
DOI:
10.1177/0091270010382912
[Indexed for MEDLINE]

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