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Intravenous AICAR a...
Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients
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- Boon, Hanneke, 1981- (författare)
- Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands
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- Bosselaar, M. (författare)
- Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
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- Praet, S. F. E. (författare)
- Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands
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- Blaak, E. E. (författare)
- Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands
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- Saris, W. H. (författare)
- Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands
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- Wagenmakers, A. J. (författare)
- School of Sport and Exercise Sciences, University of Birmingham, Birmingham, United Kingdom
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- McGee, S. L. (författare)
- Department of Physiology, University of Melbourne, Melbourne, VIC, Australia
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- Tack, C. J. (författare)
- Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
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- Smits, P. (författare)
- Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands & Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
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- Hargreaves, M. (författare)
- Department of Physiology, University of Melbourne, Melbourne, VIC, Australia
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- van Loon, L. J. (författare)
- Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, the Netherlands & Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, Netherlands
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(creator_code:org_t)
- 2008-08-16
- 2008
- Engelska.
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Ingår i: Diabetologia. - Heidelberg : Springer Berlin/Heidelberg. - 0012-186X .- 1432-0428. ; 51:10, s. 1893-1900
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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. © 2008 The Author(s).
Nyckelord
- AICAR
- AMPK
- Diabetes
- Glucose
- NEFA
- Non-esterified fatty acids
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Boon, Hanneke, 1 ...
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Bosselaar, M.
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Praet, S. F. E.
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Blaak, E. E.
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Saris, W. H.
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Wagenmakers, A. ...
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McGee, S. L.
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Tack, C. J.
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Smits, P.
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Hargreaves, M.
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van Loon, L. J.
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Diabetologia
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