Hypoglycemic effect of the hydroalcoholic extract of leaves of Averrhoa carambola L. (Oxalidaceae) / Efeito hipoglicemiante do extrato hidroalcoólico de folhas de Averrhoa carambola L. (Oxalidaceae)

O efeito do tratamento via oral (20 mg/kg x day) com extrato hidroalcoólico de folhas de Averrhoa carambola L. (EHFC) sobre a glicemia de jejum (15 h) foi examinada ao compararmos ratos que receberam veículo (Grupo controle) ou EHFC (Grupo EHFC) durante 15 dias. O grupo EHFC apresentou menor glicemia de jejum (p<0,05). Em contraste, o grupo EHFC apresentou maior (p<0,05) produção hepática glicose a partir de L-alanina (5 mM). Este efeito foi mediado, pelo menos parcialmente, pela ativação do catabolismo da L-alanina, inferido pela maior produção hepática de uréia (p<0,05) e L-lactato (p<0,05). Diferente da L-alanina, a produção hepática de glicose a partir de L-glutamina (5 mM), L-lactato (2 mM) e glicerol (2 mM) no grupo EHFC foi similar ao grupo controle. Adicionalmente, o efeito do tratamento com EHFC sobre a captação de glicose no músculo soleus, inferida pela incorporação de [14C]-glicose em glicogênio (síntese de glicogênio) e produção de [14C]-lactato foi investigada, verificando-se resultados semelhantes nos dois grupos. Assim, concluiu-se que a redução da glicemia de jejum promovida pelo tratamento com EHFC não foi mediada por inibição da gliconeogenese hepática e/ou aumento da captação muscular de glicose.

The effect of the oral treatment (20 mg/kg x day) with the hydroalcoholic extract of leaves of Averrhoa carambola L. (HELAC) on fasting glycemia (15 h) was examined. For this purpose, rats that received vehicle (Control group) or HELAC (HELAC group) during 15 days were compared. HELAC group showed lower fasting glycemia (p<0.05). In contrast, livers from HELAC group showed higher (p<0.05) glucose production from L-alanine (5 mM). This effect was mediated, at least part of it, by an activation of the catabolism of L-alanine inferred by the increased hepatic urea (p<0.05) and L-lactate (p<0.05) production. Differently of L-alanine, the glucose production from L-glutamine (5 mM), L-lactate (2 mM) and glycerol (2 mM) was similar (Control group vs. HELAC group). In addition, the HELAC treatment did not change the glucose uptake in soleus muscles, inferred by the incorporation of [14C]-glucose to glycogen (glycogen synthesis) and [14C]-lactate production. Thus, we can conclude that the reduction of fasting glycemia promoted by the treatment with HELAC was not mediated by an inhibition of hepatic gluconeogenesis and/or an increased glucose uptake by muscles.

Comparative acute effects of l-carnitine and dl-carnitine on hepatic catabolism of l-alanine and l-glutamine in rats.

AIM: To compare the acute effects of l-carnitine (LCT) and dl-carnitine (DLC) on hepatic catabolism of l-alanine and l-glutamine in rats. METHODS: Livers from 24 h fasted and fed rats were perfused in situ. The substrates l-alanine (5 mmol/L) and l-glutamine (5 mmol/L) were employed. The gluconeogenic and ureogenic activity was measured as the difference between the rates of glucose and urea released during and before the infusion of l-glutamine or l-alanine. RESULTS: LCT (60 micromol/L) but not DLC (60 micromol/L and 120 micromol/L) increased the production of glucose and urea from l-glutamine. However, neither LCT (60 micromol/L and 120 micromol/L) nor DLC (60 micromol/L and 240 micromol/L) showed any significant effect on hepatic glucose and urea production from l-alanine. CONCLUSION: The results showed a different acute effect of LCT and DLC on the activation of hepatic gluconeogenesis and ureagenesis promoted by l-glutamine, reinforcing the idea that DLC could not replace LCT.

Central role of cAMP in the inhibition of glycogen breakdown and gluconeogenesis promoted by leptin and insulin in perfused rat liver.

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.