Print Email Facebook Twitter Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice Title Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice Author Heijboer, A.C. van den Hoek, A.M. Pijl, H. Voshol, P.J. Havekes, L.M. Romijn, J.A. Corssmit, E.P.M. TNO Kwaliteit van Leven Publication year 2005 Abstract Aims/hypothesis: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Methods: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left lateral ventricle of male C57Bl/6 mice. The animals had no access to food. The control group received three injections of distilled water. Whole-body and hepatic insulin sensitivity were measured by hyperinsulinaemic-euglycaemic clamp in combination with [3H]glucose infusion. Glut4 mRNA expression was measured in skeletal muscle. Results: Plasma glucose and insulin concentrations under basal and hyperinsulinaemic conditions were similar in MTII- and placebo-treated mice. Endogenous glucose production (EGP) and glucose disposal in the basal state were significantly higher in MTII-treated mice than in the control group (71±22 vs 43±12 μmol·min-1·kg-1, p<0.01). During hyperinsulinaemia, glucose disposal was significantly higher in MTII-treated mice (151±20 vs 108±20 μmol·min -1·kg-1, p<0.01). In contrast, the inhibitory effect of insulin on EGP was not affected by MTII (relative decrease in EGP: 45±27 vs 50±20%). Glut4 mRNA expression in skeletal muscle was significantly increased in MTII-treated mice (307±94 vs 100±56%, p<0.01). Conclusions/interpretation: Intracerebroventricular administration of MTII acutely increases insulin-mediated glucose disposal but does not affect the capacity of insulin to suppress EGP in C57Bl/6 mice. These data indicate that central stimulation of melanocortin-3/4 receptors modulates insulin sensitivity in a tissue-specific manner, independent of its well-known impact on feeding and body weight. © Springer-Verlag 2005. Chemicals / CAS: glucose transporter 4, 188071-24-1; glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; melanocortin 3 receptor, 189235-81-2; melanocortin 4 receptor, 201099-18-5; tritium, 10028-17-8; water, 7732-18-5; alpha-MSH, 581-05-5; Blood Glucose; Corticosterone, 50-22-6; Fatty Acids, Nonesterified; Glucose Transporter Type 4; Glucose, 50-99-7; Insulin, 11061-68-0; melanotan-II, 121062-08-6; Monosaccharide Transport Proteins; Muscle Proteins; Peptides, Cyclic; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; RNA, Messenger; Slc2a4 protein, mouse Subject BiologyBiomedical ResearchBrainDiabetesGlut4Insulin resistanceMetabolismNeuropeptidesGlucose transporter 4Hormone receptor stimulating agentInsulinMelanocortin 3 receptorMelanocortin 4 receptorMelanotan IIMessenger RNAPlaceboTritiumUnclassified drugWaterAnimal experimentAnimal tissueBody weightBrain lateral ventricleControlled studyDistillationDrug effectFood intakeGluconeogenesisGlucose blood levelGlucose clamp techniqueGlucose metabolismHyperinsulinemiaInsulin sensitivityIsotope labelingMouseMouse strainNonhumanSkeletal muscleAlpha-MSHAnimalsBlood GlucoseCorticosteroneFatty Acids, NonesterifiedGlucoseGlucose Clamp TechniqueGlucose Transporter Type 4Injections, IntraventricularInsulinInsulin ResistanceKineticsLiverMaleMiceMice, Inbred C57BLMonosaccharide Transport ProteinsMuscle ProteinsPeptides, CyclicReceptor, Melanocortin, Type 3Receptor, Melanocortin, Type 4RNA, Messenger To reference this document use: http://resolver.tudelft.nl/uuid:67796436-bccc-4017-a38f-91a9baff280e DOI https://doi.org/10.1007/s00125-005-1838-8 TNO identifier 238642 ISSN 0012-186X Source Diabetologia, 48 (8), 1621-1626 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.