Anti-hiperglycemic effect of Quassia amara (Simaroubaceae) in normal and diabetic rats / Efeito anti-hiperglicêmico de Quassia amara (Simaroubaceae) em ratos normais e diabéticos

The anti-hyperglycemic effect of wood powder of Quassia amara (QA) was evaluated in normal and in alloxan diabetes-induced rats. After a 12 h fast and glycemic check, the animals were orally given 0.9% of saline (control group), metformin (500 mg/kg) or QA (200 mg/kg) and, 30 minutes later, they received an oral glucose dose (1g/kg). The blood glucose level was measured after 30, 60, 90 and 120 minutes. From the oral glucose dose, QA showed anti-hyperglycemic effects, similar to metformin, only in the diabetic animals (p<0.01) when compared to the control group. Although the anti-hyperglycemic mechanism of action of QA was not investigated, a mechanism similar to metformin can be suggested, since both presented similar results for the conditions tested, that is, normal and diabetic rats. It is believed that the use of QA in diabetics could help to control the blood glucose levels and be useful as an alternative therapy.

O efeito anti-hiperglicemiante do pó do lenho de Quassia amara (QA) foi avaliado em ratos normais e diabéticos aloxana induzidos. Após jejum de 12 horas e verificação da glicemia, os animais receberam administração oral de salina 0.9% (grupo controle), metformina (500 mg/kg) ou QA (200 mg/kg) e 30 minutos depois carga oral de glicose (1g/kg). A glicemia foi medida nos próximos 30, 60, 90 e 120 minutos. A partir da carga oral de glicose, a QA mostrou efeito anti-hiperglicemiante, similar a metformina, somente nos animais diabéticos (p<0.01) quando comparados ao grupo controle. Embora o mecanismo de ação anti-hiperglicemiante da QA não tenha sido investigado, podemos sugerir um mecanismo semelhante à metformina, visto que ambos apresentaram resultados similares nas duas condições testadas, ou seja, animais normais e diabéticos. Acredita-se que o uso de QA, em diabéticos, possa auxiliar no controle da glicemia e servir como terapia alternativa.

Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia.

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 microM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 microM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 microM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.

Responsiveness of glycogen breakdown to cyclic AMP in perfused liver from rats with insulin-induced hypoglycemia

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 æM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 æM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 æM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP

Rat liver responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia

Hepatic responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia was investigated. For this purpose, livers were perfused with a saturating concentration of 2 mM glycerol, 5 mM L-alanine or 5 mM L-glutamine as gluconeogenic substrates. All experiments were performed 1 h after an ip injection of saline (CN group) or 1 IU/kg of insulin (IN group). The IN group showed higher (P<0.05) hepatic glucose production from glycerol, L-alanine and L-glutamine and higher (P<0.05) production of L-lactate, pyruvate and urea from L-alanine and L-glutamine. In addition, ip injection of 100 mg/kg glycerol, L-alanine and L-glutamine promoted glucose recovery. The results indicate that the hepatic capacity to produce glucose from gluconeogenic precursors was increased during insulin-induced hypoglycemia.

Rat liver responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia.

Hepatic responsiveness to gluconeogenic substrates during insulin-induced hypoglycemia was investigated. For this purpose, livers were perfused with a saturating concentration of 2 mM glycerol, 5 mM L-alanine or 5 mM L-glutamine as gluconeogenic substrates. All experiments were performed 1 h after an ip injection of saline (CN group) or 1 IU/kg of insulin (IN group). The IN group showed higher (P<0.05) hepatic glucose production from glycerol, L-alanine and L-glutamine and higher (P<0.05) production of L-lactate, pyruvate and urea from L-alanine and L-glutamine. In addition, ip injection of 100 mg/kg glycerol, L-alanine and L-glutamine promoted glucose recovery. The results indicate that the hepatic capacity to produce glucose from gluconeogenic precursors was increased during insulin-induced hypoglycemia.

Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia.

The time-course changes of the responsiveness of glycogen breakdown to alpha- and ss-adrenergic agonists during insulin-induced hypoglycemia (IIH) were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 microM) and isoproterenol (20 microM) was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ss-adrenergic receptors showed a higher degree of adrenergic desensitization than did alpha-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the ss-receptor second messenger) were not affected by IIH.

Time sequence of changes in the responsiveness of glycogen breakdown to adrenergic agonists in perfused liver of rats with insulin-induced hypoglycemia

The time-course changes of the responsiveness of glycogen breakdown to a- and Beta-adrenergic agonists during insulin-induced hypoglycemia (IIH) were investigated. Blood glucose levels were decreased prior to the alteration in the hepatic responsiveness to adrenergic agonists. The activation of hepatic glucose production and glycogenolysis by phenylephrine (2 µM) and isoproterenol (20 µM) was decreased in IIH. The changes in the responsiveness of glycogen catabolism were first observed for isoproterenol and later for phenylephrine. Hepatic ß-adrenergic receptors showed a higher degree of adrenergic desensitization than did a-receptors. Liver glycogen synthase activity, glycogen content and the catabolic effect of dibutyryl cyclic AMP (the Beta-receptor second messenger) were not affected by IIH.

Hypoglycemia induced by insulin increases hepatic capacity to produce glucose from gluconeogenic amino acids.

AIM: To investigate the hepatic capacity to produce glucose during hypoglycemia induced by insulin (HII). METHODS: Livers from 24-h fasted rats which received i.p. insulin (HII rats) or saline (control rats) were perfused in situ. The gluconeogenic substrates L-alanine (5 mmol/L), L-glutamine (5 mmol/L), L-lactate (2 mmol/L), and glycerol (2 mmol/L) were employed. The gluconeogenic activity was measured as the difference between rates of glucose released during and before the substrate infusion. In part of the experiments the production of urea was measured. Before the liver perfusion blood was collected for determination of glycemia and insulinemia. RESULTS: HII rats showed: (a) hypoglycemia and hyperinsulinemia; (b) increased hepatic capacity to produce glucose from L-alanine and L-glutamine; (c) increased hepatic ureogenesis from L-alanine and L-glutamine; and (d) increased hepatic glucose production from glycerol. However, hepatic glucose production from L-lactate was not affected by hypoglycemia. CONCLUSION: In spite of hyperinsulinemia the hepatic capacity to produce glucose from L-glutamine and L-alanine increased during HII. These results can be attributed to the higher hepatic catabolism of both amino acids, since the ability of the liver to produce glucose was not affected by hypoglycemia.