RT Journal Article
T1 Glucagon-Like Peptide 1 (GLP-1) Can Reverse AMP-Activated Protein Kinase (AMPK) and S6 Kinase (P70S6K) Activities Induced by Fluctuations in Glucose Levels in Hypothalamic Areas Involved in Feeding Behaviour
A1 Hurtado Carneiro, Verónica
A1 Sanz Miguel, María Del Carmen
A1 Roncero Rincón, Isabel
A1 Vázquez Pérez, Patricia
A1 Blázquez Fernández, Enrique
A1 Álvarez García, Elvira
A1 Rancán, Lisa
A2 Bazán, Nicolas
AB The anorexigenic peptide, glucagon-like peptide-1 (GLP-1), reduces glucose metabolism in the human hypothalamus and brain stem. The brain activity of metabolic sensors such as AMP-activated protein kinase (AMPK) responds to changes in glucose levels. The mammalian target of rapamycin (mTOR) and its downstream target, p70S6 kinase (p70S6K), integrate nutrient and hormonal signals. The hypothalamic mTOR/p70S6K pathway has been implicated in the control of feeding and the regulation of energy balances. Therefore, we investigated the coordinated effects of glucose and GLP-1 on the expression and activity of AMPK and p70S6K in the areas involved in the control of feeding. The effect of GLP-1 on the expression and activities of AMPK and p70S6K was studied in hypothalamic slice explants exposed to low- and high-glucose concentrations by quantitative real-time RT-PCR and by the quantification of active-phosphorylated protein levels by immunoblot. In vivo, the effects of exendin-4 on hypothalamic AMPK and p70S6K activation were analysed in male obese Zucker and lean controls 1 h after exendin-4 injection to rats fasted for 48 h or after re-feeding for 2–4 h. High-glucose levels decreased the expression of Ampk in the lateral hypothalamus and treatment with GLP-1 reversed this effect. GLP-1 treatment inhibited the activities of AMPK and p70S6K when the activation of these protein kinases was maximum in both the ventromedial and lateral hypothalamic areas. Furthermore, in vivo s.c. administration of exendin-4 modulated AMPK and p70S6K activities in those areas, in both fasted and re-fed obese Zucker and lean control rats.
PB Springer
SN 1559-1182
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/94940
UL https://hdl.handle.net/20.500.14352/94940
LA eng
NO Hurtado-Carneiro, V., Sanz, C., Roncero, I. et al. Glucagon-Like Peptide 1 (GLP-1) Can Reverse AMP-Activated Protein Kinase (AMPK) and S6 Kinase (P70S6K) Activities Induced by Fluctuations in Glucose Levels in Hypothalamic Areas Involved in Feeding Behaviour. Mol Neurobiol 45, 348–361 (2012). https://doi.org/10.1007/s12035-012-8239-z
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Banco de Santander
NO Universidad Complutense de Madrid
NO Fundación Mutua Madrileña
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 10 abr 2025