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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.


Mary MacKillop Institute for Health Research

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Journal Article

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