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Type: Artigo de periódico
Title: Hypothalamic AMPK activation blocks lipopolysaccharide inhibition of glucose production in mice liver
Author: Santos, GA
Moura, RF
Vitorino, DC
Roman, EAFR
Torsoni, AS
Velloso, LA
Torsoni, MA
Abstract: 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.
Subject: AMPK
Glucose production
Country: Irlanda
Editor: Elsevier Ireland Ltd
Citation: Molecular And Cellular Endocrinology. Elsevier Ireland Ltd, v. 381, n. 41671, n. 88, n. 96, 2013.
Rights: fechado
Identifier DOI: 10.1016/j.mce.2013.07.018
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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