Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients.

H. Boon, M. Bosselaar, S.F. Praet, E.E. Blaak, W.H. Saris, A.J. Wagenmakers, S.L. McGee, C.J. Tack, P. Smits, M. Hargreaves, L.J. van Loon

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    Abstract

    AB - AIMS/HYPOTHESIS: The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients. METHODS: Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)). RESULTS: Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p < 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001). CONCLUSIONS/INTERPRETATION: The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration.
    Original languageEnglish
    Pages (from-to)1893-1900
    JournalDiabetologia
    Volume51
    Issue number10
    DOIs
    Publication statusPublished - 1 Jan 2008

    Cite this

    Boon, H., Bosselaar, M., Praet, S. F., Blaak, E. E., Saris, W. H., Wagenmakers, A. J., McGee, S. L., Tack, C. J., Smits, P., Hargreaves, M., & van Loon, L. J. (2008). Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia, 51(10), 1893-1900. https://doi.org/10.1007/s00125-008-1108-7