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Higher Insulin Sensitivity and Impaired Insulin Secretion in Cachetic Solid Ehrlich Tumour-Bearing Mice

dc.contributor.authorViolato, N. M. [UNESP]
dc.contributor.authorRafacho, A.
dc.contributor.authorBoschero, A. C.
dc.contributor.authorBosqueiro, José Roberto [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Santa Catarina (UFSC)
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.date.accessioned2015-03-18T15:54:19Z
dc.date.available2015-03-18T15:54:19Z
dc.date.issued2014-08-01
dc.description.abstractInsulin secretion is mainly regulated by blood glucose concentration. On the other hand, changes in peripheral insulin sensitivity induce compensatory adaptations in pancreatic beta-cells to maintain normoglycaemia. Tumour presence causes dramatic alterations in glucose homeostasis and insulin secretion because of the high glucose consumption by the tumour cells. Here, we investigated insulin secretion in solid Ehrlich tumour-bearing mice in association with cachexia. For that, male adult Swiss mice were subcutaneously inoculated with solid Ehrlich tumour cells and sacrificed at 14 days after tumour implantation (SET), while control mice received saline alone (CTL). Insulin secretion, following different stimuli, glucose tolerance, and insulin sensitivity as well as the expression of key proteins involved in insulin secretion was assessed. The SET group showed decreased glycaemia, insulinaemia, hepatic glycogen and body weight, and increased plasma free fatty acids and triglycerides, characteristics of cancer cachexia. A very interesting finding in this study was the development of higher glucose tolerance and insulin sensitivity in SET group. The dose-response curve of insulin secretion to increasing glucose concentrations (2.8-22.2 mM) showed an EC50 of 10 mM glucose for CTL mice and 13 mM glucose for SET mice. Insulin secretion was significantly reduced in SET islets at 30 mM KCl, 100 M carbachol, 20 mM arginine, and 20 mM leucine. Moreover, AKT, PKA, PKC, and AchRM3 expressions were reduced by 17 % to 24 % in SET animals. These results, mainly the augmented insulin sensitivity, show that SET is an interesting model to study alterations in pancreatic function and carbohydrate metabolism in cancer cachexia.en
dc.description.affiliationSao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil
dc.description.affiliationUniv Fed Santa Catarina, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP, Brazil
dc.description.affiliationSao Paulo State Univ UNESP, Fac Sci, Dept Phys Educ, BR-17033360 Bauru, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ UNESP, Fac Sci, Dept Phys Educ, BR-17033360 Bauru, SP, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent615-620
dc.identifierhttp://dx.doi.org/10.1055/s-0034-1370967
dc.identifier.citationHormone And Metabolic Research. Stuttgart: Georg Thieme Verlag Kg, v. 46, n. 9, p. 615-620, 2014.
dc.identifier.doi10.1055/s-0034-1370967
dc.identifier.issn0018-5043
dc.identifier.lattes2423477869556138
dc.identifier.urihttp://hdl.handle.net/11449/116878
dc.identifier.wosWOS:000341100000004
dc.language.isoeng
dc.publisherGeorg Thieme Verlag Kg
dc.relation.ispartofHormone And Metabolic Research
dc.relation.ispartofjcr2.560
dc.relation.ispartofsjr0,918
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectcachexiaen
dc.subjectpancreatic beta-cellsen
dc.subjectprotein expressionen
dc.titleHigher Insulin Sensitivity and Impaired Insulin Secretion in Cachetic Solid Ehrlich Tumour-Bearing Miceen
dc.typeArtigo
dcterms.rightsHolderGeorg Thieme Verlag Kg
unesp.author.lattes2423477869556138
unesp.author.orcid0000-0003-3829-8570[3]
unesp.author.orcid0000-0002-8637-6097[2]
unesp.author.orcid0000-0001-5367-7427[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências, Baurupt
unesp.departmentEducação Física - FCpt

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