Print Email Facebook Twitter Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice Title Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice Author Heijboer, A.C. van den Hoek, A.M. Parlevliet, E.T. Havekes, L.M. Romijn, J.A. Pijl, H. Corssmit, E.P.M. TNO Kwaliteit van Leven Publication year 2006 Abstract Aims/hypothesis: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin, we also determined the metabolic effects of growth hormone releasing peptide 6 (GHRP-6), a specific GHS receptor agonist. In addition, we explored the biological significance of des-ghrelin (unacylated ghrelin) in this experimental context. Materials and methods: Vehicle (n=8), ghrelin (n=9), GHRP-6 (n=9), des-ghrelin (n=8) or a combination of des-ghrelin and ghrelin (n=7) were infused i.v. for 3 h. Simultaneously, endogenous glucose production and glucose disposal were measured by 14C-glucose dilution during a hyperinsulinaemic-euglycaemic clamp. Tissue-specific glucose uptake in muscle and adipose tissue was measured using 3H-2-deoxyglucose. Results: During hyperinsulinaemia, glucose disposal was 31% higher in mice treated with ghrelin than in those treated with vehicle (77±16 and 59±8 μmol kg-1 h-1, respectively, p<0.05). This was in accordance with enhanced 2-deoxyglucose uptake in muscle in ghrelin-treated animals. In contrast, endogenous glucose production was less effectively suppressed by insulin during ghrelin infusion (46±22 vs 71±11% in controls, p<0.05). GHRP-6 did not affect insulin action. Des-ghrelin hampered insulin's capacity to inhibit endogenous glucose production, whereas it did not affect glucose disposal. The restraining effects of des-ghrelin and ghrelin on hepatic insulin action were abolished by simultaneous administration of both peptides. Conclusions/interpretation: Ghrelin hampers insulin's capacity to suppress endogenous glucose production, whereas it reinforces the action of insulin on glucose disposal, independently of food intake and body weight. These metabolic effects are unlikely to be mediated by the GHS receptor. Furthermore, simultaneous administration of des-ghrelin abolishes the inhibitory effect of ghrelin on hepatic insulin action. © Springer-Verlag 2006. Chemicals / CAS: deoxyglucose, 154-17-6; ghrelin, 258279-04-8, 304853-26-7; glucose, 50-99-7, 84778-64-3; histidyl dextro tryptophylalanyltryptophyl dextro phenylalanyllysinamide, 87616-84-0; insulin, 9004-10-8; ghrelin; Glucose, 50-99-7; Insulin, 11061-68-0; Peptide Hormones Subject BiologyBiomedical ResearchAnimal modelsGHRP-6Glucose metabolismGut hormoneHyperinsulinaemic- euglycaemic clamp techniqueInsulin resistanceTracer methodologyDeoxyglucoseDesoctanoylghrelinGhrelinGrowth hormone secretagogue receptorGrowth hormone secretagogue receptor stimulating agentHistidyl dextro tryptophylalanyltryptophyl dextro phenylalanyllysinamidePeptide derivativeUnclassified drugAdipose tissueAdolescentBody weightControlled studyFood intakeGlucogenesisGlucose clamp techniqueGlucose metabolismHormone actionHyperinsulinemiaInsulin sensitivityIsotope dilution assayLiver metabolismMouseMuscle metabolismNonhumanAnimalsBody WeightGlucoseHepatocytesInsulinMaleMiceMice, Inbred C57BLPeptide Hormones To reference this document use: http://resolver.tudelft.nl/uuid:801bf3e3-d37a-4f6f-a4aa-c358e61e76d1 DOI https://doi.org/10.1007/s00125-006-0138-2 TNO identifier 239214 ISSN 0012-186X Source Diabetologia, 49 (4), 732-738 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.