Metabolic effects of IGF-I in diabetic rats.
Insulinlike growth factor I (IGF-I) stimulates glucose utilization (GU) in nondiabetic rats. We compared the effects of IGF-I and insulin on glucose metabolism in control (fed plasma glucose 7.7 +/- 0.1 mM, n = 30) and partially (90%) pancreatectomized diabetic (plasma glucose 18.4 +/- 0.8 mM, n = 30) awake unstressed rats. IGF-I was infused at 0.65 or 1.96 nmol.kg-1.min-1 and insulin at 22 or 29 pmol.kg-1.min-1 in combination with [3-3H]glucose while euglycemia was maintained by a variable glucose infusion. In controls, GU during the 0.65- and 1.96-nmol.kg-1.min-1 IGF-I infusions (127 +/- 7 and 168 +/- 4 mumol.kg-1.min-1, respectively) was similar to rates observed during the 22- and 29-pmol.kg-1.min-1 insulin infusions (121 +/- 2 and 156 +/- 5 mumol.kg-1.min-1). Whole-body glycolytic rate (3H2O generation) and muscle glycogen synthetic rate were identical during insulin and IGF-I infusions. In diabetic rats, GU was reduced by 30% versus control rats (P less than 0.01) during both the low-dose (88 +/- 7 vs. 121 +/- 7 mumol.kg-1.min-1) and higher-dose (109 +/- 4 vs. 156 +/- 5 mumol.kg-1.min-1) insulin clamps. The defect in insulin action involved both muscle glycogen synthesis and glycolysis. In diabetic rats, IGF-I elicited rates of GU similar to controls (115 +/- 10 and 164 +/- 12 mumol.kg-1.min-1 during the 0.65- and 1.96-nmol.kg-1.min-1 infusions, respectively) and corrected the intracellular defects in glycogen synthesis and glycolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Rossetti
L
L
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7886.
Frontoni
S
S
Dimarchi
R
R
DeFronzo
R A
RA
Giaccari
A
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006019:Glycolysis / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007332:Insulin Infusion Systems; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D005947:Glucose