Metabolic effects of IGF-I and insulin in spontaneously diabetic BB/w rats.
To examine the influence of insulin-dependent diabetes on the metabolic response to insulin-like growth factor I (IGF-I), awake chronically catheterized diabetic and nondiabetic BB/w rats received IGF-I (5 micrograms.kg-1.min-1) or insulin (2 mU.kg-1.min-1) for 2 h while maintaining euglycemia. In nondiabetic rats, IGF-I and insulin produced similar twofold increases in glucose uptake, but insulin was more effective in reducing hepatic glucose production (90 +/- 15 vs. 5 +/- 11%; P less than 0.001) and beta-hydroxybutyrate levels (94 +/- 1 vs. 19 +/- 6%; P less than 0.001). In diabetic rats, insulin-stimulated glucose uptake was impaired (8.5 +/- 0.9 vs. 11.5 +/- 0.9 mg.kg-1.min-1 in nondiabetics; P less than 0.05). In contrast, IGF-I-stimulated glucose uptake was identical in diabetic and nondiabetic rats. Furthermore, IGF-I suppressed glucose production by 73% (P less than 0.01) and caused a greater lowering of beta-hydroxybutyrate levels (from 2.9 +/- 0.8 to 0.8 +/- 0.3 mumol/l) in diabetic rats. We conclude that 1) the capacity of IGF-I infusion to stimulate glucose uptake is maintained in spontaneously diabetic BB rats that are insulin resistant, and 2) IGF-I infusion suppresses elevated glucose production rates and plasma ketone concentrations in diabetic rats but is relatively ineffective in nondiabetic rats. Thus the metabolic responses to infused IGF-I do not appear to be diminished in diabetic rats with impaired responses to insulin.
Jacob
R J
RJ
Department of Medicine, Yale School of Medicine, New Haven, Connecticut 06510.
Sherwin
R S
RS
Bowen
L
L
Fryburg
D
D
Fagin
K D
KD
Tamborlane
W V
WV
Shulman
G I
GI
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007657:Ketone Bodies / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D011865:Radioisotope Dilution Technique; D051381:Rats; D011913:Rats, Inbred BB; D011994:Recombinant Proteins / Q000494:pharmacology; D014316:Tritium
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D007657:Ketone Bodies; D011994:Recombinant Proteins; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D005947:Glucose