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Am J Physiol Endocrinol Metab 291: E1360-E1364, 2006. First published July 18, 2006; doi:10.1152/ajpendo.00188.2006
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Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production

Marion A. M. den Boer,1 Peter J. Voshol,1 Folkert Kuipers,3 Johannes A. Romijn,1 and Louis M. Havekes1,2,4

1Department of Endocrinology and Metabolism, Leiden University Medical Center; 2The Netherlands Organization for Applied Scientific Research Quality of Life, Gaubius Laboratory, Leiden; 3Department of Pediatrics, University Medical Center, Groningen; and 4 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

Submitted 19 April 2006 ; accepted in final form 4 July 2006

Insulin is an important inhibitor of both hepatic glucose output and hepatic VLDL-triglyceride (VLDL-TG) production. We investigated whether both processes are equally sensitive to insulin-mediated inhibition. To test this, we used euglycemic clamp studies with four increasing plasma concentrations of insulin in wild-type C57Bl/6 mice. By extrapolation, we estimated that half-maximal inhibition of hepatic glucose output and hepatic VLDL-TG production by insulin were obtained at plasma insulin levels of ~3.6 and ~6.8 ng/ml, respectively. In the same experiments, we measured that half-maximal decrease of plasma free fatty acid levels and half-maximal stimulation of peripheral glucose uptake were reached at plasma insulin levels of ~3.0 and ~6.0 ng/ml, respectively. We conclude that, compared with insulin sensitivity of hepatic glucose output, peripheral glucose uptake and hepatic VLDL-TG production are less sensitive to insulin.

very-low-density lipoprotein; fatty acid; euglycemic hyperinsulinemic clamp; liver


Address for reprint requests and other correspondence: M. A. M. den Boer, Leiden Univ. Medical Center, Dept. of Endocrinology and Metabolism, C4-R, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands (e-mail: A.M.den_Boer{at}lumc.nl)






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