title: Melanocortin-4 receptor activation promotes insulin-stimulated mTOR signaling.
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.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Biaoxin
authors.initials: B
authors.lastname: Chai
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Li
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wu
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mulholland
mesh_terms: D000345:Affinity Labels / Q000378:metabolism / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D007004:Hypoglycemic Agents / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D007004:Hypoglycemic Agents; D007328:Insulin; D044105:Receptor, Melanocortin, Type 4; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; D000242:Cyclic AMP; D058570:TOR Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C031143:AICA ribonucleotide