H. Boon, M. Bosselaar, Stephan F. E. Praet
Aug 16, 2008
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2
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Journal
Diabetologia
Abstract
AbstractAims/hypothesisThe 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.MethodsStable 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).ResultsPlasma glucose rate of appearance (Ra) was reduced following AICAR administration, while plasma glucose rate of disappearance (Rd) was similar in the AICAR and control test. Consequently, blood glucose disposal (Rd expressed as a percentage of Ra) 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 Ra and Rd 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/interpretationThe 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. Trial registration: ISRCTN31384581 Funding: The study was funded by the Dutch Diabetes Research Foundation. S. L. McGee is a National Health and Medical Research Council (NHMRC) Peter Doherty Fellow (400446).