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

Boon, H., Bosselaar, M., Praet, S., Blaak, E.E., Saris, W.H.M., Wagenmakers, A.J.M., McGee, Sean L., Tack, C.J., Smits, P., Hargreaves, Mark and van Loon, L.J.C. 2008, Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients, Diabetologia, vol. 51, no. 10, pp. 1893-1900.

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Title Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients
Author(s) Boon, H.
Bosselaar, M.
Praet, S.
Blaak, E.E.
Saris, W.H.M.
Wagenmakers, A.J.M.
McGee, Sean L.
Tack, C.J.
Smits, P.
Hargreaves, Mark
van Loon, L.J.C.
Journal name Diabetologia
Volume number 51
Issue number 10
Start page 1893
End page 1900
Total pages 8
Publisher Springer Berlin / Heidelberg
Place of publication Heidelberg, Germany
Publication date 2008-10
ISSN 0012-186X
1432-0428
Summary 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/m2).
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.
Language eng
Field of Research 060114 Systems Biology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, The Author(s)
Persistent URL http://hdl.handle.net/10536/DRO/DU:30025031

Document type: Journal Article
Collections: School of Medicine
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Created: Fri, 12 Mar 2010, 11:49:02 EST by Sean McGee

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