Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Roustit, M. M.; Vaughan, J. M.; Jamieson, Pauline; Cleasby, M E (2014)
Publisher: Bioscientifica Ltd
Languages: English
Types: Article
Subjects: glucose disposal, urocortin 3, AMPK, PI3K signalling, skeletal muscle, Research, GLUT4
Insulin resistance (IR) in skeletal muscle is an important component of both type 2 diabetes and the syndrome of sarcopaenic obesity, for which there are no effective therapies. Urocortins (UCNs) are not only well established as neuropeptides but also have their roles in metabolism in peripheral tissues. We have shown recently that global overexpression of UCN3 resulted in muscular hypertrophy and resistance to the adverse metabolic effects of a high-fat diet. Herein, we aimed to establish whether short-term local UCN3 expression could enhance glucose disposal and insulin signalling in skeletal muscle. UCN3 was found to be expressed in right tibialis cranialis and extensor digitorum longus muscles of rats by in vivo electrotransfer and the effects studied vs the contralateral muscles after 1 week. No increase in muscle mass was detected, but test muscles showed 19% larger muscle fibre diameter (P=0.030), associated with increased IGF1 and IGF1 receptor mRNA and increased SER256 phosphorylation of forkhead transcription factor. Glucose clearance into the test muscles after an intraperitoneal glucose load was increased by 23% (P=0.018) per unit mass, associated with increased GLUT1 (34% increase; P=0.026) and GLUT4 (48% increase; P=0.0009) proteins, and significantly increased phosphorylation of insulin receptor substrate-1, AKT, AKT substrate of 160 kDa, glycogen synthase kinase-3β, AMP-activated protein kinase and its substrate acetyl coA carboxylase. Thus, UCN3 expression enhances glucose disposal and signalling in muscle by an autocrine/paracrine mechanism that is separate from its pro-hypertrophic effects, implying that such a manipulation may have promised for the treatment of IR syndromes including sarcopaenic obesity.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • Abo T, Iida RH, Kaneko S, Suga T, Yamada H, Hamada Y & Yamane A 2012 IGF and myostatin pathways are respectively induced during the earlier and the later stages of skeletal muscle hypertrophy induced by clenbuterol, a b(2)-adrenergic agonist. Cell Biochemistry and Function 30 671-676. (doi:10.1002/cbf.2848)
    • Anderson SB, Goldberg AL & Whitman M 2008 Identification of a novel pool of extracellular pro-myostatin in skeletal muscle. Journal of Biological Chemistry 283 7027-7035. (doi:10.1074/jbc.M706678200)
    • Baehr LM, Tunzi M & Bodine SC 2014 Muscle hypertrophy is associated with increases in proteasome activity that is independent of MuRF1 and MAFbx expression. Frontiers in Physiology 5 69. (doi:10.3389/fphys.2014.00069)
    • Bale TL, Anderson KR, Roberts AJ, Lee KF, Nagy TR & Vale WW 2003 Corticotropin-releasing factor receptor-2-deficient mice display abnormal homeostatic responses to challenges of increased dietary fat and cold. Endocrinology 144 2580-2587. (doi:10.1210/en.2002-0091)
    • Bassil MS & Gougeon R 2013 Muscle protein anabolism in type 2 diabetes. Current Opinion in Clinical Nutrition and Metabolic Care 16 83-88. (doi:10.1097/MCO.0b013e32835a88ee)
    • Brar BK, Stephanou A, Knight R & Latchman DS 2002 Activation of protein kinase B/Akt by urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death. Journal of Molecular and Cellular Cardiology 34 483-492. (doi:10.1006/jmcc.2002.1529)
    • Brar BK, Jonassen AK, Egorina EM, Chen A, Negro A, Perrin MH, Mjos OD, Latchman DS, Lee KF & Vale W 2004 Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury: an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart. Endocrinology 145 24-35 discussion 21-23. (doi:10.1210/en.2003-0689)
    • Carlin KM, Vale WW & Bale TL 2006 Vital functions of corticotropinreleasing factor (CRF) pathways in maintenance and regulation of energy homeostasis. PNAS 103 3462-3467. (doi:10.1073/pnas. 0511320103)
    • Chan TM & Exton JH 1976 A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes. Analytical Biochemistry 71 96-105. (doi:10.1016/ 0003-2697(76)90014-2) Stephanou AA,KniUghtRD, THsuSY, HHsueh AJ O&LatcRhman DS 20C05
    • Chanalaris A, Lawrence KM, Townsend PA, Davidson S, Jamshidi Y, Hypertrophic effects of urocortin homologous peptides are mediated via activation of the Akt pathway. Biochemical and Biophysical Research Communications 328 442-448. (doi:10.1016/j.bbrc.2005.01.001)
    • Chao H, Digruccio M, Chen P & Li C 2012 Type 2 corticotropin-releasing factor receptor in the ventromedial nucleus of hypothalamus is critical in regulating feeding and lipid metabolism in white adipose tissue. Endocrinology 153 166-176. (doi:10.1210/en.2011-1312)
    • Chen A, Blount A, Vaughan J, Brar B & Vale W 2004 Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: localization, basal expression in corticotropin-releasing factor receptor (CRFR) 1- and CRFR2-null mice, and regulation by glucocorticoids. Endocrinology 145 2445-2457. (doi:10.1210/en.2003-1570)
    • Chen A, Brar B, Choi CS, Rousso D, Vaughan J, Kuperman Y, Kim SN, Donaldson C, Smith SM, Jamieson P et al. 2006 Urocortin 2 modulates glucose utilization and insulin sensitivity in skeletal muscle. PNAS 103 16580-16585. (doi:10.1073/pnas.0607337103)
    • Chen P, Vaughan J, Donaldson C, Vale W & Li C 2010 Injection of urocortin 3 into the ventromedial hypothalamus modulates feeding, blood glucose levels, and hypothalamic POMC gene expression but not the HPA axis. American Journal of Physiology. Endocrinology and Metabolism 298 E337-E345. (doi:10.1152/ajpendo.00402.2009)
    • Cleasby ME, Davey JR, Reinten TA, Graham MW, James DE, Kraegen EW & Cooney GJ 2005 Acute bidirectional manipulation of muscle glucose uptake by in vivo electrotransfer of constructs targeting glucose transporter genes. Diabetes 54 2702-2711. (doi:10.2337/diabetes.54.9.2702)
    • Cleasby ME, Reinten TA, Cooney GJ, James DE & Kraegen EW 2007 Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression. Molecular Endocrinology 21 215-228. (doi:10.1210/me.2006-0154)
    • Cleasby ME, Jarmin S, Eilers W, Elashry M, Andersen DK, Dickson G & Foster K 2014 Local overexpression of the myostatin propeptide increases glucose transporter expression and enhances skeletal muscle glucose disposal. American Journal of Physiology. Endocrinology and Metabolism 306 E814-E823. (doi:10.1152/ajpendo.00586.2013)
    • Crosson SM, Khan A, Printen J, Pessin JE & Saltiel AR 2003 PTG gene deletion causes impaired glycogen synthesis and developmental insulin resistance. Journal of Clinical Investigation 111 1423-1432. (doi:10.1172/JCI17975)
    • DeFronzo RA & Tripathy D 2009 Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 32(Suppl 2) S157-S163. (doi:10.2337/dc09-S302)
    • Di Cola G, Cool MH & Accili D 1997 Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. Journal of Clinical Investigation 99 2538-2544. (doi:10.1172/JCI119438)
    • Hinkle RT, Donnelly E, Cody DB, Bauer MB & Isfort RJ 2003 Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function. Endocrinology 144 4939-4946. (doi:10.1210/en.2003-0271)
    • Hsu SY & Hsueh AJ 2001 Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor. Nature Medicine 7 605-611. (doi:10.1038/87936)
    • Jamieson PM, Cleasby ME, Kuperman Y, Morton NM, Kelly PA, Brownstein DG, Mustard KJ, Vaughan JM, Carter RN, Hahn CN et al. 2011 Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. Diabetologia 54 2392-2403. (doi:10.1007/s00125-011-2205-6)
    • Keipert S, Ost M, Johann K, Imber F, Jastroch M, Van Schothorst EM, Keijer J & Klaus S 2013 Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through induction of FGF21 as a myokine. American Journal of Physiology. Endocrinology and Metabolism 306 E469-E482. (doi:10.1152/ajpendo.00330.2013)
    • Kuizon E, Pearce EG, Bailey SG, Chen-Scarabelli C, Yuan Z, Abounit K, McCauley RB, Saravolatz L, Faggian G, Mazzucco A et al. 2009
    • Reutenauer-Patte J, Boittin FX, Patthey-Vuadens O, Ruegg UT & Dorchies inhibiting FOXO transcription factors. Molecular Cell 14 395-403. function through both PKA- and Epac-dependent pathways. American Tsatsanis C, Androulidaki A, Alissafi T, Charalampopoulos I, Dermitzaki E, Journal of Pathology 180 749-762. (doi:10.1016/j.ajpath.2011.10.038) Roger T, Gravanis A & Margioris AN 2006 Corticotropin-releasing factor
    • Reyes TM, Lewis K, Perrin MH, Kunitake KS, Vaughan J, Arias CA, and the urocortins induce the expression of TLR4 in macrophages via Hogenesch JB, Gulyas J, Rivier J, Vale WW et al. 2001 Urocortin II: a activation of the transcription factors PU.1 and AP-1. Journal of member of the corticotropin-releasing factor (CRF) neuropeptide Immunology 176 1869-1877. (doi:10.4049/jimmunol.176.3.1869) family that is selectively bound by type 2 CRF receptors. PNAS 98 Vaughan JM, Rivier J, Corrigan AZ, McClintock R, Campen CA, Jolley D, 2843-2848. (doi:10.1073/pnas.051626398) Voglmayr JK, Bardin CW, Rivier C & Vale W 1989 Detection and
    • Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, purification of inhibin using antisera generated against synthetic Yancopoulos GD & Glass DJ 2001 Mediation of IGF-1-induced skeletal peptide fragments. Methods in Enzymology 168 588-617. (doi:10.1016/ myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 0076-6879(89)68044-5) pathways. Nature Cell Biology 3 1009-1013. (doi:10.1038/ncb1101-1009) Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan
    • Sandri M, Lin J, Handschin C, Yang W, Arany ZP, Lecker SH, Goldberg AL & R, Turnbull AV, Lovejoy D, Rivier C et al. 1995 Urocortin, a mammalian Spiegelman BM 2006 PGC-1a protects skeletal muscle from atrophy by neuropeptide related to fish urotensin I and to corticotropin-releasing suppressing FoxO3 action and atrophy-specific gene transcription. factor. Nature 378 287-292. (doi:10.1038/378287a0) PNAS 103 16260-16265. (doi:10.1073/pnas.0607795103) Venkatasubramanian S, Griffiths ME, McLean SG, Miller MR, Luo R, Lang
    • Solinas G, Summermatter S, Mainieri D, Gubler M, Montani JP, Seydoux J, NN & Newby DE 2013 Vascular effects of urocortins 2 and 3 in healthy Smith SR & Dulloo AG 2006 Corticotropin-releasing hormone directly volunteers. Journal of the American Heart Association 2 e004267. stimulates thermogenesis in skeletal muscle possibly through substrate (doi:10.1161/JAHA.112.004267) cycling between de novo lipogenesis and lipid oxidation. Endocrinology Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, 147 31-38. (doi:10.1210/en.2005-1033) Cinti S, Lowell B, Scarpulla RC et al. 1999 Mechanisms controlling
    • Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB & Ferrucci L mitochondrial biogenesis and respiration through the thermogenic 2008 Sarcopenic obesity: definition, cause and consequences. Current coactivator PGC-1. Cell 98 115-124. (doi:10.1016/S0092-8674(00) Opinion in Clinical Nutrition and Metabolic Care 11 693-700. (doi:10. 80611-X) 1097/MCO.0b013e328312c37d) Zheng B, Ohkawa S, Li H, Roberts-Wilson TK & Price SR 2010 FOXO3a
    • Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez mediates signaling crosstalk that coordinates ubiquitin and atroginM, Yancopoulos GD & Glass DJ 2004 The IGF-1/PI3K/Akt pathway 1/MAFbx expression during glucocorticoid-induced skeletal muscle prevents expression of muscle atrophy-induced ubiquitin ligases by atrophy. FASEB Journal 24 2660-2669. (doi:10.1096/fj.09-151480)
  • No related research data.
  • Discovered through pilot similarity algorithms. Send us your feedback.

Share - Bookmark

Funded by projects

Cite this article