Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production.
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 approximately 3.6 and approximately 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 approximately 3.0 and approximately 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.
den Boer
Marion A M
MA
Dept. of Endocrinology and Metabolism, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands. A.M.den_Boer@lumc.nl
Voshol
Peter J
PJ
Kuipers
Folkert
F
Romijn
Johannes A
JA
Havekes
Louis M
LM
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000096:biosynthesis*; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000096:biosynthesis*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D005947:Glucose