Decreased hepatic gluconeogenesis in transgenic rats with increased circulating angiotensin-(1-7)

作者：Bilman Victor; Mares Guia Lucas; Nadu Ana Paula; Bader Michael; Campagnole Santos Maria Jose; Santos Robson Augusto S; Santos Sergio Henrique S^*

来源：Peptides, 2012, 37(2): 247-251.

DOI：10.1016/j.peptides.2012.08.002

The renin-angiotensin (Ang) system (RAS) plays an important role in the control of glucose metabolism and glycemia. Several studies demonstrated that the effects of angiotensin-(1-7) are mainly opposite to the actions of biological angiotensin II. Recent studies have demonstrated that rats with increased circulating angiotensin-(1-7), acting through the G protein coupled receptor Mas, have enhanced glucose tolerance and insulin sensitivity, presenting improved metabolic parameters. However, there is no data regarding the role of angiotensin-(1-7)-Mas axis in hepatic glycemic metabolism. In the present study, the gluconeogenesis and glycogenolysis was investigated in Sprague-Dawley (SD) and in TGR(A1-7)3292 (TGR) rats which present approximately twofold increase in plasma Ang-(1-7) levels compared to SD. The pyruvate administration in fasted rats showed a decreased synthesis of glucose in TGR compared to the SD rats, pointing to a downregulation of gluconeogenesis. Supporting this data, the mRNA evaluation of gluconeogenic enzymes showed a significant reduction in phosphoenolpyruvate carboxykinase reinforced by a significantly diminished expression of hepatocyte nuclear factor 4 alpha (HNF-4 alpha), responsible for the regulation of gluconeogenic enzymes. In conclusion our data show that the improved glucose metabolism induced by Ang-(1-7) could be due, at least in part, to a downregulation of hepatic gluconeogenesis.

• 出版日期2012-10