title: Central role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis promoted by leptin and insulin in perfused rat liver.
abstract: Leptin showed less prominent inhibiting effect on the activation of hepatic glycogen breakdown and gluconeogenesis promoted by cAMP. The role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis induced by physiological levels of leptin (10 ng/ml) and insulin (20 microU/ml) in the perfused liver was investigated. Insulin but not leptin inhibited (p < 0.05) the activation of glycogen breakdown promoted by cAMP (3 microM). Contrary to cAMP, the activation of glycogen catabolism promoted by 8-Br-cAMP (0.3 microM), a cAMP analogue more resistant to hydrolysis by phosphodiesterase 3B (PD3B), was inhibited (p < 0.05) not only by insulin (20 microU/ml) but also by leptin (10 ng/ml). The effect of leptin, however, was less intense than that of insulin. To verify the participation of the intracellular levels of cAMP, the experiments were repeated with N(6)-monobutyryl-cAMP (N(6)-MB-cAMP), a cAMP analogue, which is not metabolized by PD3B. The activation of glycogen breakdown promoted by N(6)-MB-cAMP (0.3 microM) was not affected by leptin or insulin. In agreement with the results regarding glycogen catabolism, insulin and leptin at 50 ng/ml but not leptin at 10 ng/ml inhibited (p < 0.05) the activation of gluconeogenesis promoted by cAMP (7.5 microM). Taken together, these results led us to postulate that the convergent signaling pathways of these two hormones causing the inhibition of glycogen catabolism and gluconeogenesis involve a reduction of intracellular cAMP. Thus, cAMP levels may play an important role in the cross talk between both hormones and for the insulin-like effects of leptin.
authors.affiliation: Department of Physiological Sciences, State University of Londrina, 86055-900, Londrina, PR, Brasil.
authors.forename: Glaucia R
authors.initials: GR
authors.lastname: Borba-Murad
authors.forename: Márcia
authors.initials: M
authors.lastname: Vardanega-Peicher
authors.forename: Sharize B
authors.initials: SB
authors.lastname: Galende
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Helenir M
authors.initials: HM
authors.lastname: Souza
authors.forename: Erica G
authors.initials: EG
authors.lastname: Mario
authors.forename: Bruna K
authors.initials: BK
authors.lastname: Bassoli
authors.forename: Roberto B
authors.initials: RB
authors.lastname: Bazotte
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects* / Q000502:physiology; D006003:Glycogen / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D020738:Leptin; D006003:Glycogen; D000242:Cyclic AMP