title: α-MSH Stimulates Glucose Uptake in Mouse Muscle and Phosphorylates Rab-GTPase-Activating Protein TBC1D1 Independently of AMPK.
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.
authors.affiliation: Steno Diabetes Center, Translational Pathophysiology, 2820 Gentofte, Denmark.
authors.forename: Cathrine Laustrup
authors.initials: CL
authors.lastname: Møller
authors.affiliation: Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Kjøbsted
authors.affiliation: Monash Obesity & Diabetes Institute, Metabolic Neurophysiology Laboratory, Monash University, 3168 Clayton, Australia.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Enriori
authors.affiliation: Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Thomas Elbenhardt
authors.initials: TE
authors.lastname: Jensen
authors.affiliation: Department of Pediatrics, Centenary Hospital for Women, Youth and Children and Australian National University, 2605 Canberra, Australia.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garcia-Rudaz
authors.affiliation: Monash Obesity & Diabetes Institute, Metabolic Neurophysiology Laboratory, Monash University, 3168 Clayton, Australia.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Litwak
authors.affiliation: Incretin and Obesity Biology, Novo Nordisk A/S, 2760 Maaloev, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Raun
authors.affiliation: Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Wojtaszewski
authors.affiliation: Incretin and Obesity Biology, Novo Nordisk A/S, 2760 Maaloev, Denmark.
authors.forename: Birgitte Schjellerup
authors.initials: BS
authors.lastname: Wulff
authors.affiliation: Monash Obesity & Diabetes Institute, Metabolic Neurophysiology Laboratory, Monash University, 3168 Clayton, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D000521:alpha-MSH / Q000494:pharmacology*
chemical_list: D020690:GTPase-Activating Proteins; C095906:Tbc1d1 protein, mouse; D000521:alpha-MSH; D055372:AMP-Activated Protein Kinases; D005947:Glucose