Diabetes, Vol 39, Issue 3 340-347, Copyright © 1990 by American Diabetes Association
Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs
A Giacca, R Gupta, S Efendic, K Hall, A Skottner, L Lickley and M Vranic
Department of Physiology, University of Toronto, Canada.
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)