Melanocortin-4 receptor activation promotes insulin-stimulated mTOR signaling

Peptides. 2010 Oct;31(10):1888-93. doi: 10.1016/j.peptides.2010.06.028. Epub 2010 Jul 31.

Abstract

The melanocortin signaling system is integral in regulating energy homeostasis. The melanocortin-4 receptor (MC4R) activates several signaling pathways in performance of this function. The effect of MC4R on insulin-stimulated mammalian target of rapamycin (mTOR), a cellular energy sensor, signaling was investigated. The GT1-1 cell line which expresses MC4R expression was utilized. mTOR signaling was measured by Western blotting analysis using Phospho-mTOR (Ser2448) antibody. NDP-MSH dose-dependently enhanced insulin-stimulated mTOR phosphorylation. The MC4R antagonist SHU9119 blocked this effect, demonstrating specificity. The protein kinase A - cyclic AMP pathway and the MAP kinase pathway were not involved in NDP-MSH actions on insulin-stimulated mTOR phosphorylation. In contrast, the AMP-activated protein kinase agonist, AICAR, attenuated this effect. MC4R activation potentiates insulin-stimulated mTOR signaling via the AMPK pathway.

MeSH terms

  • Affinity Labels / metabolism
  • Affinity Labels / pharmacology
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / metabolism
  • Animals
  • Cell Line
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation
  • Hypoglycemic Agents / metabolism
  • Insulin / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Receptor, Melanocortin, Type 4 / metabolism*
  • Ribonucleotides / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism*
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / metabolism
  • alpha-MSH / pharmacology

Substances

  • Affinity Labels
  • Hypoglycemic Agents
  • Insulin
  • Receptor, Melanocortin, Type 4
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • alpha-MSH
  • MSH, 4-Nle-7-Phe-alpha-
  • Cyclic AMP
  • TOR Serine-Threonine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • AICA ribonucleotide