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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Hypothalamic AMPK activation blocks lipopolysaccharide inhibition of glucose production in mice liver

Texto completo
Autor(es):
Santos, G. A. [1] ; Moura, R. F. [1] ; Vitorino, D. C. [2] ; Roman, E. A. F. R. [1] ; Torsoni, A. S. [3] ; Velloso, L. A. [1] ; Torsoni, M. A. [3]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Aplicadas, Dept Med Interna, Campinas, SP - Brazil
[2] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Fisiol & Biofis, Campinas, SP - Brazil
[3] Univ Estadual Campinas UNICAMP, Fac Ciencias Aplicadas, BR-13484350 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Molecular and Cellular Endocrinology; v. 381, n. 1-2, p. 88-96, DEC 5 2013.
Citações Web of Science: 10
Resumo

Endotoxic hypoglycaemia has an important role in the survival rates of septic patients. Previous studies have demonstrated that hypothalamic AMP-activated protein kinase (hyp-AMPK) activity is sufficient to modulate glucose homeostasis. However, the role of hyp-AMPK in hypoglycaemia associated with endotoxemia is unknown. The aims of this study were to examine hyp-AMPK dephosphorylation in lipopolysaccharide (LPS)-treated mice and to determine whether pharmacological hyp-AMPK activation could reduce the effects of endotoxemia on blood glucose levels. LPS-treated mice showed reduced food intake, diminished basal glycemia, increased serum TNF-alpha and IL-1 beta levels and increased hypothalamic p-TAK and TLR4/MyD88 association. These effects were accompanied by hyp-AMPK/ACC dephosphorylation. LPS-treated mice also showed diminished liver expression of PEPCK/G6Pase, reduction in p-FOXO1, p-AMPK, p-STAT3 and p-JNK level and glucose production. Pharmacological hyp-AMPK activation blocked the effects of LPS on the hyp-AMPK phosphorylation, liver PEPCK expression and glucose production. Furthermore, the effects of LPS were TLR4-dependent because hyp-AMPK phosphorylation, liver PEPCK expression and fasting glycemia were not affected in TLR4-mutant mice. These results suggest that hyp-AMPK activity may be an important pharmacological target to control glucose homeostasis during endotoxemia. (C) 2013 Elsevier Ireland Ltd. All rights reserved. (AU)

Processo FAPESP: 10/14034-6 - Modulação do metabolismo hepático da glicose pela ativação de vias inflamatórias: a participação das proteínas AMPK e Toll Like Receptor (TLR4) hipotalâmicas
Beneficiário:Gustavo Aparecido dos Santos
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 11/17656-0 - A modulação da AMPK hipotalâmica e da homeostase energética por LPS: a participação de toll like receptor-4 (TLR-4)
Beneficiário:Marcio Alberto Torsoni
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/16775-6 - Ativação de "toll like receptor" (TLR) no hipotálamo de ratos e a modulação do balanço energético: o papel das proteínas AMPK/ACC e mTOR
Beneficiário:Daniele Cristina Vitorino
Linha de fomento: Bolsas no Brasil - Doutorado