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Type: Artigo de periódico
Title: Hypothalamic Ampk Activation Blocks Lipopolysaccharide Inhibition Of Glucose Production In Mice Liver.
Author: Santos, G A
Moura, R F
Vitorino, D C
Roman, E A F R
Torsoni, A S
Velloso, L A
Torsoni, M A
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-α and IL-1β 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.
Subject: Acetyl-coa Carboxylase
Adenylate Kinase
Blood Glucose
Enzyme Activation
Gene Expression Regulation, Enzymologic
Mice, Inbred C3h
Mice, Transgenic
Phosphoenolpyruvate Carboxykinase (gtp)
Protein Processing, Post-translational
Toll-like Receptor 4
Tumor Necrosis Factor-alpha
Glucose Production
Citation: Molecular And Cellular Endocrinology. v. 381, n. 1-2, p. 88-96, 2013-Dec.
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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