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

M. Bosselaar, P. Smits, L.J. van Loon, C.J. Tack

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1449-1458
Number of pages10
JournalJournal of Clinical Pharmacology
Volume51
Issue number10
DOIs
Publication statusPublished - Oct 2011

Keywords

  • AICAR
  • euglycemic hyperinsulinemic clamp
  • glucose infusion rate
  • forearm glucose uptake
  • forearm blood flow
  • ACTIVATED PROTEIN-KINASE
  • HUMAN SKELETAL-MUSCLE
  • STIMULATED GLUCOSE-TRANSPORT
  • ADENOSINE-REGULATING AGENT
  • WHOLE-BODY
  • EPITROCHLEARIS MUSCLE
  • FATTY-ACID
  • BLOOD-FLOW
  • IN-VIVO
  • INSULIN

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