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Effects of physical exercise on the MKP-3/FoxO1 association in liver of obese and diabetic mice

Grant number: 11/13779-0
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): July 31, 2013
Field of knowledge:Health Sciences - Physical Education
Principal researcher:Eduardo Rochete Ropelle
Grantee:Luciana Santos Souza Pauli
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

Abstract

Hyperglycemia is one of the hallmarks of type 2 diabetes. The liver is the main organ responsible for controlling the glucose production. The transcription factor FoxO1 (family transcription factor forkhead box O) is a key molecule for the control of hepatic glucose production. In diabetic rodents there is a severe reduction of FoxO1 phosphorylation and increased nuclear translocation of FoxO1 in liver cells. Nuclear FoxO1 is associated with PGC1alfa (PPAR coactivator 1alpha) and increases the gene expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) inducing hyperglycemia. Recently, the protein MKP-3 (MAPK phosphatase-3) was described as an important FoxO1 activity modulator in the liver of diabetic rodents. MKP-3 is able to associate with and dephosphorylate FoxO1 in the liver, resulting in increased gluconeogenesis and hyperglycemia. Therefore, inhibition of hepatic MKP-3 expression represents an attractive opportunity to prevent hyperglycemia and diabetes. Exercise is one of the most widely used non-pharmacological strategies to improve the glycemic profile in diabetic patients; however, exercise actions in the liver are poorly explored. The objective of this study is to investigate the effects of exercise on the MKP-3 expression and its interaction with FoxO1 in the liver of obese and diabetic animals. We believe this project will provide new insights into the mechanism by which exercise controls the hepatic glucose production.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SOUZA PAULI, LUCIANA SANTOS; CHIARREOTTO ROPELLE, ELOIZE CRISTINA; DE SOUZA, CLAUDIO TEODORO; CINTRA, DENNYS ESPER; RAMOS DA SILVA, ADELINO SANCHEZ; RODRIGUES, BARBARA DE ALMEIDA; DE MOURA, LEANDRO PEREIRA; MARINHO, RODOLFO; DE OLIVEIRA, VANESSA; KATASHIMA, CARLOS KIYOSHI; PAULI, JOSE RODRIGO; ROPELLE, EDUARDO ROCHETE. Exercise training decreases mitogen-activated protein kinase phosphatase-3 expression and suppresses hepatic gluconeogenesis in obese mice. JOURNAL OF PHYSIOLOGY-LONDON, v. 592, n. 6, p. 1325-1340, MAR 15 2014. Web of Science Citations: 17.
CHIARREOTTO-ROPELLE, ELOIZE C.; PAULI, LUCIANA S. S.; KATASHIMA, CARLOS K.; PIMENTEL, GUSTAVO D.; PICARDI, PATY K.; SILVA, VAGNER R. R.; DE SOUZA, CLAUDIO T.; PRADA, PATRICIA O.; CINTRA, DENNYS E.; CARVALHEIRA, JOSE B. C.; ROPELLE, EDUARDO R.; PAULI, JOSE R. Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 305, n. 5, p. E649-E659, SEP 2013. Web of Science Citations: 24.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.