Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs.
The effects of equipotent glucose-lowering doses of insulinlike growth factor I (IGF-I) and insulin on tracer-determined glucose kinetics and several metabolites were compared in 14 experiments (7 in each group) in fasted, totally depancreatized dogs. This model prevented variations in insulin secretion induced by IGF-I and permitted evaluation of the effects of IGF-I on extrapancreatic glucagon. Steady-state moderate hyperglycemia (9.9 +/- 0.2 mM) was maintained by a subbasal intraportal infusion of insulin (1.29 +/- 0.17 pmol.kg-1.min-1). This was continued throughout the experiment, allowing evaluation of IGF-I effects on insulin clearance. Human recombinant IGF-I or insulin was given intravenously as a primed infusion for 90 min, followed by a 50-min recovery period. The dose of IGF-I was a 2.6-nmol/kg bolus plus 57.4 pmol.kg-1.min-1. The insulin dose required to induce the same plasma glucose decline as IGF-I (44 +/- 6 vs. 43 +/- 5%, NS) was 9-12 times lower (0.06-nmol/kg bolus + 6.4 +/- 0.6 pmol.kg-1.min-1). However, the mechanism of this decline differed with IGF-I and insulin; glucose production was much less suppressed (25 +/- 9 vs. 42 +/- 11%, P less than 0.001) and glucose utilization was more stimulated (68 +/- 18 vs. 38 +/- 19%, P less than 0.05) with IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, University of Toronto, Canada.
A
A
Giacca
R
R
Gupta
S
S
Efendic
K
K
Hall
A
A
Skottner
L
L
Lickley
M
M
Vranic
D000818:Animals; D004285:Dogs; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D010180:Pancreatectomy; D013002:Somatomedins / Q000494:pharmacology*
D007328:Insulin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D005947:Glucose