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 potass ium balance in isolated perfused rat livers. At 1 nM, both IGF-I and insuli n decreased basal glucose release by approximate to 64% (P < 0.05). Adrenal ine (epinephrine)stimulated glucose release (42.6 +/- 4.5 mu mol/g of liver within 30 min) was inhibited (P < 0.05) by approximate to 32 and approxima te to 52% during IGF-I and insulin exposure, which was accompanied by reduc ed cAMP release(-71 and -80%, P < 0.05). IGF-I- and insulin-induced reducti on of glucose release only decreased during calcium-free perfusion, but not during inhibition of phosphoinositide 3-kinase by wortmannin. Both IGF-I a nd insulin induced net potassium uptake, while insulin also attenuated the response to adrenaline. In conclusion, IGF-I causes (i) insulinlike inhibit ion of hepatic glycogenolysis, even at low, nanomolar concentrations, which is associated with decreased cAMP release, reduced in the absence of Ca2+, but not mediated by phosphoinositide 3-kinase, (ii) reduction of adrenalin e-induced glycogenolysis and (iii) net potassium uptake under basal conditi ons.