PMID- 20603172 OWN - NLM STAT- MEDLINE DCOM- 20110131 LR - 20211203 IS - 1873-5169 (Electronic) IS - 0196-9781 (Print) IS - 0196-9781 (Linking) VI - 31 IP - 10 DP - 2010 Oct TI - Melanocortin-4 receptor activation promotes insulin-stimulated mTOR signaling. PG - 1888-93 LID - 10.1016/j.peptides.2010.06.028 [doi] AB - 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. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Chai, Biaoxin AU - Chai B AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Li, Ji-Yao AU - Li JY FAU - Zhang, Weizhen AU - Zhang W FAU - Wu, Xiaobin AU - Wu X FAU - Zhang, Chao AU - Zhang C FAU - Mulholland, Michael W AU - Mulholland MW LA - eng GR - R01 DK054032/DK/NIDDK NIH HHS/United States GR - R01 DK054032-14/DK/NIDDK NIH HHS/United States GR - R37 DK043225/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20100731 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Affinity Labels) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Receptor, Melanocortin, Type 4) RN - 0 (Ribonucleotides) RN - 360-97-4 (Aminoimidazole Carboxamide) RN - 581-05-5 (alpha-MSH) RN - 75921-69-6 (MSH, 4-Nle-7-Phe-alpha-) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - F0X88YW0YK (AICA ribonucleotide) SB - IM MH - Affinity Labels/metabolism/pharmacology MH - Aminoimidazole Carboxamide/analogs & derivatives/metabolism MH - Animals MH - Cell Line MH - Cyclic AMP/metabolism MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Enzyme Activation MH - Hypoglycemic Agents/metabolism MH - Insulin/*metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Receptor, Melanocortin, Type 4/*metabolism MH - Ribonucleotides/metabolism MH - Signal Transduction/drug effects/*physiology MH - TOR Serine-Threonine Kinases/*metabolism MH - alpha-MSH/analogs & derivatives/metabolism/pharmacology PMC - PMC3282553 MID - NIHMS226184 EDAT- 2010/07/07 06:00 MHDA- 2011/02/01 06:00 PMCR- 2012/02/20 CRDT- 2010/07/07 06:00 PHST- 2010/04/30 00:00 [received] PHST- 2010/06/23 00:00 [revised] PHST- 2010/06/24 00:00 [accepted] PHST- 2010/07/07 06:00 [entrez] PHST- 2010/07/07 06:00 [pubmed] PHST- 2011/02/01 06:00 [medline] PHST- 2012/02/20 00:00 [pmc-release] AID - S0196-9781(10)00272-X [pii] AID - 10.1016/j.peptides.2010.06.028 [doi] PST - ppublish SO - Peptides. 2010 Oct;31(10):1888-93. doi: 10.1016/j.peptides.2010.06.028. Epub 2010 Jul 31.