Effects of insulin-like growth factor I on basal and stimulated glucose fluxes in rat liver.
Effects of insulin-like growth factor I (IGF-I) and insulin on glucose and potassium fluxes were examined by measuring transhepatic glucose and potassium balance in isolated perfused rat livers. At 1 nM, both IGF-I and insulin decreased basal glucose release by approximately 64% (P < 0.05). Adrenaline (epinephrine)-stimulated glucose release (42.6 +/- 4.5 micromol/g of liver within 30 min) was inhibited (P < 0.05) by approximately 32 and approximately 52% during IGF-I and insulin exposure, which was accompanied by reduced cAMP release (-71 and -80%, P < 0.05). IGF-I- and insulin-induced reduction of glucose release only decreased during calcium-free perfusion, but not during inhibition of phosphoinositide 3-kinase by wortmannin. Both IGF-I and insulin induced net potassium uptake, while insulin also attenuated the response to adrenaline. In conclusion, IGF-I causes (i) insulin-like inhibition of hepatic glycogenolysis, even at low, nanomolar concentrations, which is associated with decreased cAMP release, reduced in the absence of Ca(2+), but not mediated by phosphoinositide 3-kinase, (ii) reduction of adrenaline-induced glycogenolysis and (iii) net potassium uptake under basal conditions.
Englisch
R
R
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Wurzinger
R
R
Fürnsinn
C
C
Schneider
B
B
Frisch
H
H
Waldhäusl
W
W
Graf
J
J
Roden
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017082:Portal Pressure / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077191:Wortmannin
D000730:Androstadienes; D002118:Calcium; D000242:Cyclic AMP; D006152:Cyclic GMP; D004837:Epinephrine; D005947:Glucose; D006003:Glycogen; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D019344:Lactic Acid; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011188:Potassium; D000077191:Wortmannin