Effects of insulin deficiency or excess on hepatic gluconeogenic flux during glycogenolytic inhibition in the conscious dog.
The direct acute effects of insulin on the regulation of hepatic gluconeogenic flux to glucose-6-phosphate (G6P) in vivo may be masked by the hormone's effects on net hepatic glycogenolytic flux and the resulting changes in glycolysis. To investigate this possibility, we used a glycogen phosphorylase inhibitor (BAY R3401) to inhibit glycogen breakdown in the overnight-fasted dog, and the effects of complete insulin deficiency or a fourfold rise in the plasma insulin level were assessed during a 5-h experimental period. Hormone levels were controlled using somatostatin with portal insulin and glucagon infusion. After the control period, plasma insulin infusion 1) was discontinued, creating insulin deficiency; 2) increased fourfold; or 3) was continued at the basal rate. During insulin deficiency, glucose production and the plasma level and net hepatic uptake of nonesterified free fatty acids increased, whereas during hyperinsulinemia they decreased. Net hepatic lactate uptake increased sixfold during insulin deficiency and 2.5-fold during hyperinsulinemia. Net hepatic gluconeogenic flux increased more than fourfold during insulin deficiency but was not reduced by hyperinsulinemia. We conclude that in the absence of appreciable glycogen breakdown, an acute gluconeogenic effect of hypoinsulinemia becomes manifest, whereas inhibition of the process by a physiologic rise in insulin was not evident.
Edgerton
Dale S
DS
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. dale.edgerton@vanderbilt.edu
Cardin
Sylvain
S
Pan
Catherine
C
Neal
Doss
D
Farmer
Ben
B
Converse
Margaret
M
Cherrington
Alan D
AD
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005663:Furans / Q000494:pharmacology*; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology; D005943:Gluconeogenesis / Q000502:physiology*; D006019:Glycolysis; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D007329:Insulin Antagonists / Q000494:pharmacology*; D007700:Kinetics; D007773:Lactates / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D013004:Somatostatin / Q000494:pharmacology
D000596:Amino Acids; C413462:BAY R3401; D004095:Dihydropyridines; D005663:Furans; D007328:Insulin; D007329:Insulin Antagonists; D007773:Lactates; D008112:Liver Glycogen; D013004:Somatostatin; D005934:Glucagon