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Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect
Bosselaar, Marlies Smits, Paul van Loon, Luc J. C. Tack, Cees J.
Bosselaar, Marlies
Smits, Paul
van Loon, Luc J. C.
Tack, Cees J.
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 hyperinsulinemia 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.
Keywords
AICAR, euglycemic hyperinsulinemic clamp, glucose infusion rate, forearm glucose uptake, forearm blood flow
Date
2011
Type
Journal article
Journal
Journal of Clinical Pharmacology
Book
Volume
51
Issue
10
Page Range
1449-1458
Article Number
ACU Department
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Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled