title: Importance of substrate changes in the decrease of hepatic glucose cycling during insulin infusion and declining glycemia in the depancreatized dog.
abstract: We wished to determine whether the elevated glucose cycling (GC) between glucose and glucose-6-phosphate (G<-->G6P) in diabetes can be reversed with acute insulin treatment. In six insulin-deprived, anesthetized, depancreatized dogs, insulin was infused for 6-9 h at a starting dose of 45-150 pmol.kg-1.min-1 to normalize plasma glucose from 23.9 +/- 1.4 to 5.0 +/- 0.4 mmol/l and gradually decreased to and maintained at a basal rate (1.7 +/- 1.0 pmol.kg-1.min-1) during the last 3 h. GC, measured with [2-3H]- and [6-3H]glucose, fell markedly from 15.3 +/- 2.7 and normalized at 1.3 +/- 0.6 mumol.kg-1.min-1 (P < 0.001). This occurred because total hepatic glucose output fell much more (from 41.2 +/- 3.1 to 11.6 +/- 1.2) than did glucose production (from 25.9 +/- 1.9 to 10.3 +/- 1.0 mumol.kg-1.min-1) (both P < 0.01). Freeze-clamped liver biopsies were taken at timed intervals for measurements of hepatic enzymes and substrates. The elevated hepatic hexose-6-phosphate levels decreased with insulin infusion (151 +/- 24 vs. 71 +/- 13 nmol/g, P < 0.01). Maximal activities of glucose-6-phosphatase (G6Pase) (from 17.6 +/- 0.8 to 19.6 +/- 2.6 U/g) and glucokinase (from 1.1 +/- 0.2 to 1.0 +/- 0.2 U/g) did not change. Insulin infusion resulted in a threefold increase (P < 0.05) in the activity of glycogen synthase (active form), but had no effect on hepatic glycogen content.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Shi
authors.forename: A
authors.initials: A
authors.lastname: Giacca
authors.forename: S
authors.initials: S
authors.lastname: Fisher
authors.forename: H
authors.initials: H
authors.lastname: Vidal
authors.forename: G
authors.initials: G
authors.lastname: van de Werve
authors.forename: M
authors.initials: M
authors.lastname: Vranic
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D010180:Pancreatectomy; D015219:Substrate Cycling
chemical_list: D001786:Blood Glucose; D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D005941:Glucokinase; D005952:Glucose-6-Phosphatase; D005947:Glucose