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

被引:36
作者
Bilman, Victor [2 ]
Mares-Guia, Lucas [2 ]
Nadu, Ana Paula [2 ]
Bader, Michael [4 ]
Campagnole-Santos, Maria Jose [2 ]
Santos, Robson Augusto S. [2 ]
Santos, Sergio Henrique S. [1 ,3 ]
机构
[1] Univ Fed Minas Gerais, Dept Pharmacol, Biol Sci Inst ICB, BR-31270901 Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Physiol, Biol Sci Inst ICB, Natl Inst Sci & Technol INCT NanoBiofar, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Estadual Montes Claros, Lab Hlth Sci, Postgrad Program Hlth Sci, Montes Claros, MG, Brazil
[4] Max Delbruck Ctr Mol Med MDC, Berlin, Germany
关键词
PYRUVATE-CARBOXYLASE; METABOLISM; EXPRESSION; MAS; DEFICIENCY; LIVER;
D O I
10.1016/j.peptides.2012.08.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:247 / 251
页数:5
相关论文
共 19 条
[1]  
Aronoff SL., 2004, Diabetes Spect, V17, P183, DOI DOI 10.2337/DIASPECT.17.3.183
[2]   Gluconeogenesis activation after intravenous angiotensin II in freely moving rats [J].
Coimbra, CC ;
Garofalo, MAR ;
Foscolo, DRC ;
Xavier, AR ;
Migliorini, RH .
PEPTIDES, 1999, 20 (07) :823-827
[3]   Cardiovascular actions of angiotensin-(1-7) [J].
Ferreira, AJ ;
Santos, RAS .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 2005, 38 (04) :499-507
[4]   Regulation of gluconeogenesis by Kruppel-like factor 15 [J].
Gray, Susan ;
Wang, Baiqiu ;
Orihuela, Yvette ;
Hong, Eun-Gyoung ;
Fisch, Sudeshna ;
Haldar, Saptarsi ;
Cline, Gary W. ;
Kim, Jason K. ;
Peroni, Odile D. ;
Kahn, Barbara B. ;
Jain, Mukesh K. .
CELL METABOLISM, 2007, 5 (04) :305-312
[5]   Mas deficiency in FVB/N mice produces marked changes in lipid and glycemic metabolism [J].
Henrique S. Santos, Sergio ;
Rodrigues Fernandes, Luciana ;
Mario, Erica Guilhen ;
Versiani M. Ferreira, Adaliene ;
Cristina J. Porto, Laura ;
Isaura Alvarez-Leite, Jaqueline ;
Maria Botion, Leida ;
Bader, Michael ;
Alenina, Natalia ;
Augusto S. Santos, Robson .
DIABETES, 2008, 57 (02) :340-347
[6]   Glucagon regulation of energy metabolism [J].
Heppner, Kristy M. ;
Habegger, Kirk M. ;
Day, Jonathan ;
Pfluger, Paul T. ;
Perez-Tilve, Diego ;
Ward, Brian ;
Gelfanov, Vasily ;
Woods, Steve C. ;
DiMarchi, Richard ;
Tschoep, Matthias .
PHYSIOLOGY & BEHAVIOR, 2010, 100 (05) :545-548
[7]   Cloning, sequencing and expression of rat liver pyruvate carboxylase [J].
Jitrapakdee, S ;
Booker, GW ;
Cassady, I ;
Wallace, JC .
BIOCHEMICAL JOURNAL, 1996, 316 :631-637
[8]   The rat pyruvate carboxylase gene structure - Alternate promoters generate multiple transcripts with the 5'-end heterogeneity [J].
Jitrapakdee, S ;
Booker, GW ;
Cassady, AI ;
Wallace, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20522-20530
[9]   Structure, mechanism and regulation of pyruvate carboxylase [J].
Jitrapakdee, Sarawut ;
St Maurice, Martin ;
Rayment, Ivan ;
Cleland, W. Wallace ;
Wallace, John C. ;
Attwood, Paul V. .
BIOCHEMICAL JOURNAL, 2008, 413 (03) :369-387
[10]  
Jones CG, 2003, BIOCHEM J, V289, P169