Decreased hepatic gluconeogenesis in transgenic rats with increased circulating angiotensin-(1-7).
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 4α (HNF-4α), 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.
National Institute of Science and Technology (INCT-NanoBiofar), Physiology Department, Biological Sciences Institute (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
Victor
V
Bilman
Lucas
L
Mares-Guia
Ana Paula
AP
Nadu
Michael
M
Bader
Maria José
MJ
Campagnole-Santos
Robson Augusto S
RA
Santos
Sérgio Henrique S
SH
Santos
D000803:Angiotensin I / Q000097:blood*; D000818:Animals; D005943:Gluconeogenesis; D008099:Liver / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7)