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

Diabetologia
H BoonL J C van Loon

Abstract

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. 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)). 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...Continue Reading

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