Molecular Neurobiology

, Volume 45, Issue 2, pp 348–361

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

  • Verónica Hurtado-Carneiro
  • Carmen Sanz
  • Isabel Roncero
  • Patricia Vazquez
  • Enrique Blazquez
  • Elvira Alvarez
Article

DOI: 10.1007/s12035-012-8239-z

Cite this article as:
Hurtado-Carneiro, V., Sanz, C., Roncero, I. et al. Mol Neurobiol (2012) 45: 348. doi:10.1007/s12035-012-8239-z

Abstract

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.

Keywords

AMPK Control of feeding Antidiabetogenic agents Hypothalamus mTOR/S6K Zucker rats 

Supplementary material

12035_2012_8239_MOESM1_ESM.doc (26 kb)
ESM 1(DOC 25 kb)
12035_2012_8239_MOESM2_ESM.doc (32 kb)
ESM 2(DOC 32 kb)
12035_2012_8239_Fig8_ESM.gif (154 kb)
ESM 3

(GIF 154 kb)

12035_2012_8239_MOESM3_ESM.eps (3.9 mb)
High Resolution Image (EPS 3957 kb)

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Verónica Hurtado-Carneiro
    • 1
    • 2
  • Carmen Sanz
    • 1
    • 2
    • 3
  • Isabel Roncero
    • 1
    • 2
  • Patricia Vazquez
    • 2
    • 4
  • Enrique Blazquez
    • 1
    • 2
  • Elvira Alvarez
    • 1
    • 2
    • 5
  1. 1.Department of Biochemistry and Molecular Biology, Faculty of Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)Complutense UniversityMadridSpain
  2. 2.The Center for Biomedical Research in Diabetes and Associated Metabolic Disorders (CIBERDEM)BarcelonaSpain
  3. 3.Department of Cell Biology, Faculty of MedicineComplutense University of MadridMadridSpain
  4. 4.3D Lab (Development, Differentiation and Degeneration), Department of Cellular and Molecular Medicine, Centro de Investigaciones BiológicasConsejo Superior de Investigaciones CientíficasMadridSpain
  5. 5.Departamento de Bioquímica y Biología Molecular, Facultad de MedicinaUniversidad ComplutenseMadridSpain

Personalised recommendations