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Am J Physiol Endocrinol Metab 289: E941-E947, 2005. First published July 5, 2005; doi:10.1152/ajpendo.00195.2005
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Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production

Peter E. Carey,1 Jean Gerrard,1 Gary W. Cline,2 Chiara Dalla Man,3 Philip T. English,4 Michael J. Firbank,5 Claudio Cobelli,3 and Roy Taylor1

1School of Clinical Medical Sciences (Diabetes); 5Institute for Ageing and Health, University of Newcastle; 4Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom; 2Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut; and 3Department of Information Engineering, University of Padova, Padova, Italy

Submitted 4 May 2005 ; accepted in final form 4 July 2005

To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and 1H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 ± 0.01 mmol/l at –10 min, P = 0) and throughout the postprandial period (0.03 ± 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 ± 0.4 vs. 10.1 ± 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 ± 99.9 vs. 909 ± 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 ± 0.58 µmol·kg–1·min–1 placebo vs. 11.17 ± 0.89 mg·kg–1·min–1 acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 ± 1.52 vs. 3.69 ± 1.21 µmol·kg–1·min–1 at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content (r = –0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.

intrahepatic triglyceride; acipimox; 1H magnetic resonance spectroscopy



Address for reprint requests and other correspondence: R. Taylor, Dept. of Medicine, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK (e-mail roy.taylor{at}ncl.ac.uk)




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