α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors Enriori, Pablo J., Chen, Weiyi, Garcia-Rudaz, Maria C., Grayson, Bernadette E., Evans, Anne E., Comstock, Sarah M., Gebhardt, Ursel, Müller, Hermann L., Reinehr, Thomas, Henry, Belinda A., Brown, Russell D., Bruce, Clinton R., Simonds, Stephanie E., Litwak, Sara A., McGee, Sean L., Luquet, Serge, Martinez, Sarah, Jastroch, Martin, Tschöp, Matthias H., Watt, Matthew J., Clarke, Iain J., Roth, Christian L., Grove, Kevin L. and Cowley, Michael A. 2016, α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors, Molecular metabolism, vol. 5, no. 10, pp. 807-822, doi: 10.1016/j.molmet.2016.07.009. Attached Files Name Description MIMEType Size Downloads bruce-amelanocytestimulationg-2016.pdf Published version application/pdf 1.83MB 145 Title α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors Author(s) Enriori, Pablo J. Chen, Weiyi Garcia-Rudaz, Maria C. Grayson, Bernadette E. Evans, Anne E. Comstock, Sarah M. Gebhardt, Ursel Müller, Hermann L. Reinehr, Thomas Henry, Belinda A. Brown, Russell D. Bruce, Clinton R. orcid.org/0000-0002-0515-3343 Simonds, Stephanie E. Litwak, Sara A. McGee, Sean L. orcid.org/0000-0001-6953-106X Luquet, Serge Martinez, Sarah Jastroch, Martin Tschöp, Matthias H. Watt, Matthew J. Clarke, Iain J. Roth, Christian L. Grove, Kevin L. Cowley, Michael A. Journal name Molecular metabolism Volume number 5 Issue number 10 Start page 807 End page 822 Total pages 16 Publisher Elsevier Place of publication Amsterdam, The Netherlands Publication date 2016-10 ISSN 2212-8778 Keyword(s) Glucose homeostasis MC5R PKA Pituitary Skeletal muscles α-MSH Summary OBJECTIVE: Central melanocortin pathways are well-established regulators of energy balance. However, scant data exist about the role of systemic melanocortin peptides. We set out to determine if peripheral α-melanocyte stimulating hormone (α-MSH) plays a role in glucose homeostasis and tested the hypothesis that the pituitary is able to sense a physiological increase in circulating glucose and responds by secreting α-MSH. METHODS: We established glucose-stimulated α-MSH secretion using humans, non-human primates, and mouse models. Continuous α-MSH infusions were performed during glucose tolerance tests and hyperinsulinemic-euglycemic clamps to evaluate the systemic effect of α-MSH in glucose regulation. Complementary ex vivo and in vitro techniques were employed to delineate the direct action of α-MSH via the melanocortin 5 receptor (MC5R)-PKA axis in skeletal muscles. Combined treatment of non-selective/selective phosphodiesterase inhibitor and α-MSH was adopted to restore glucose tolerance in obese mice. RESULTS: Here we demonstrate that pituitary secretion of α-MSH is increased by glucose. Peripheral α-MSH increases temperature in skeletal muscles, acts directly on soleus and gastrocnemius muscles to significantly increase glucose uptake, and enhances whole-body glucose clearance via the activation of muscle MC5R and protein kinase A. These actions are absent in obese mice, accompanied by a blunting of α-MSH-induced cAMP levels in skeletal muscles of obese mice. Both selective and non-selective phosphodiesterase inhibition restores α-MSH induced skeletal muscle glucose uptake and improves glucose disposal in obese mice. CONCLUSION: These data describe a novel endocrine circuit that modulates glucose homeostasis by pituitary α-MSH, which increases muscle glucose uptake and thermogenesis through the activation of a MC5R-PKA-pathway, which is disrupted in obesity. Language eng DOI 10.1016/j.molmet.2016.07.009 Field of Research 111699 Medical Physiology not elsewhere classified Socio Economic Objective 920104 Diabetes HERDC Research category C1 Refereed article in a scholarly journal ERA Research output type C Journal article Copyright notice ©2016, The Authors Free to Read? Yes Use Rights Persistent URL http://hdl.handle.net/10536/DRO/DU:30085478 Document type: Journal Article Collections: Faculty of Health School of Exercise and Nutrition Sciences Institute for Physical Activity and Nutrition Open Access Collection Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Thu, 18 Aug 2016, 05:00:36 EST Thu, 18 Aug 2016, 12:16:59 EST Thu, 18 Aug 2016, 13:53:05 EST Wed, 07 Sep 2016, 06:09:20 EST Wed, 12 Oct 2016, 13:53:00 EST Wed, 12 Oct 2016, 13:58:46 EST Wed, 12 Oct 2016, 14:00:06 EST Wed, 09 Nov 2016, 11:50:35 EST Wed, 11 Jan 2017, 09:48:29 EST Tue, 21 Feb 2017, 15:52:42 EST Tue, 21 Feb 2017, 15:54:47 EST Fri, 07 Sep 2018, 12:22:37 EST Filtered Full Citation counts:   Cited 20 times in TR Web of Science Cited 20 times in Scopus Search Google Scholar Access Statistics: 416 Abstract Views, 146 File Downloads  -  Detailed Statistics Created: Thu, 18 Aug 2016, 12:16:57 EST

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