α-MSH stimulates glucose uptake in mouse muscle and phosphorylates Rab-GTPase-activating protein TBC1D1 independently of AMPK

Cathrine Laustrup Møller, Rasmus Kjøbsted, Pablo J. Enriori, Thomas Elbenhardt Jensen, Cecilia Garcia-Rudaz, Sara A. Litwak, Kirsten Raun, Jørgen Wojtaszewski, Birgitte Schjellerup Wulff, Michael A. Cowley

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4 Citations (Scopus)

Abstract

The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate -MSH stimulation in both wild type and AMPK deficient mice. We found that -MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that -MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation.

Original languageEnglish
Article numbere0157027
Number of pages18
JournalPLoS ONE
Volume11
Issue number7
DOIs
Publication statusPublished - 28 Jul 2016

Keywords

  • phosphorylation
  • glucose
  • glucose signalling
  • soleus muscles
  • mouse models
  • insulin
  • muscle differentiation
  • obesity

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