Submitted on April 19, 2006
Accepted on July 4, 2006
Hepatic Glucose Production is More Sensitive to Insulin-mediated Inhibition than Hepatic VLDL-triglyceride Production
Marion A.M. den Boer1*, Peter J. Voshol1, Folkert Kuipers2, Johannes A. Romijn3, and Louis M. Havekes4
1 Department of Endocrinology, C4R, Leiden University Medical Center, Leiden, Netherlands
2 Department of Pediatrics, University Medical Center Groningen, Groningen, Netherlands
3 Department of Endocrinology, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands
4 Department of Endocrinology, C4R, Leiden University Medical Center, Leiden, Netherlands; Quality of Life, TNO, Leiden, Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands
* To whom correspondence should be addressed. E-mail: a.m.den_boer{at}lumc.nl.
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, in comparison to insulin sensitivity of hepatic glucose output, peripheral glucose uptake and hepatic VLDL-TG production are less sensitive to insulin.
