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Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production

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Author: Boer, M.A.M. den · Voshol, P.J. · Kuipers, F. · Romijn, J.A. · Havekes, L.M.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:American Journal of Physiology - Endocrinology and Metabolism, 6, 291
Identifier: 239769
doi: doi:10.1152/ajpendo.00188.2006
Keywords: Biology · Biomedical Research · Euglycemic hyperinsulinemic clamp · Fatty acid · Very-low-density lipoprotein · Insulin · Adipose tissue · Animal experiment · Aanimal model · Controlled study · Drug effect · Drug inhibition · Fatty acid blood level · Gluconeogenesis · Glucose infusion · Glucose transport · Hyperinsulinemia · Insulin blood level · Insulin resistance · Insulin sensitivity · Lipolysis · Liver function · Mouse · Nonhuman · Animals · Blood Glucose · Dose-Response Relationship, Drug · Fatty Acids, Nonesterified · Glucose · Glucose Clamp Technique · Hypoglycemic Agents · Insulin · Kinetics · Lipoproteins, VLDL · Liver · Male · Mice · Mice, Inbred C57BL · Triglycerides

Abstract

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. Copyright © 2006 the American Physiological Society. Chemicals / CAS: insulin, 9004-10-8; Blood Glucose; Fatty Acids, Nonesterified; Glucose, 50-99-7; Hypoglycemic Agents; Insulin, 11061-68-0; Lipoproteins, VLDL; Triglycerides