Higher Insulin Sensitivity and Impaired Insulin Secretion in Cachetic Solid Ehrlich Tumour-Bearing Mice
dc.contributor.author | Violato, N. M. [UNESP] | |
dc.contributor.author | Rafacho, A. | |
dc.contributor.author | Boschero, A. C. | |
dc.contributor.author | Bosqueiro, José Roberto [UNESP] | |
dc.contributor.institution | Universidade Estadual Paulista (Unesp) | |
dc.contributor.institution | Universidade Federal de Santa Catarina (UFSC) | |
dc.contributor.institution | Universidade Estadual de Campinas (UNICAMP) | |
dc.date.accessioned | 2015-03-18T15:54:19Z | |
dc.date.available | 2015-03-18T15:54:19Z | |
dc.date.issued | 2014-08-01 | |
dc.description.abstract | Insulin 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.affiliation | Sao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil | |
dc.description.affiliation | Univ Fed Santa Catarina, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC, Brazil | |
dc.description.affiliation | Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Campinas, SP, Brazil | |
dc.description.affiliation | Sao Paulo State Univ UNESP, Fac Sci, Dept Phys Educ, BR-17033360 Bauru, SP, Brazil | |
dc.description.affiliationUnesp | Sao Paulo State Univ, Inst Biosci, Botucatu, SP, Brazil | |
dc.description.affiliationUnesp | Sao Paulo State Univ UNESP, Fac Sci, Dept Phys Educ, BR-17033360 Bauru, SP, Brazil | |
dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) | |
dc.format.extent | 615-620 | |
dc.identifier | http://dx.doi.org/10.1055/s-0034-1370967 | |
dc.identifier.citation | Hormone And Metabolic Research. Stuttgart: Georg Thieme Verlag Kg, v. 46, n. 9, p. 615-620, 2014. | |
dc.identifier.doi | 10.1055/s-0034-1370967 | |
dc.identifier.issn | 0018-5043 | |
dc.identifier.lattes | 2423477869556138 | |
dc.identifier.uri | http://hdl.handle.net/11449/116878 | |
dc.identifier.wos | WOS:000341100000004 | |
dc.language.iso | eng | |
dc.publisher | Georg Thieme Verlag Kg | |
dc.relation.ispartof | Hormone And Metabolic Research | |
dc.relation.ispartofjcr | 2.560 | |
dc.relation.ispartofsjr | 0,918 | |
dc.rights.accessRights | Acesso restrito | |
dc.source | Web of Science | |
dc.subject | cachexia | en |
dc.subject | pancreatic beta-cells | en |
dc.subject | protein expression | en |
dc.title | Higher Insulin Sensitivity and Impaired Insulin Secretion in Cachetic Solid Ehrlich Tumour-Bearing Mice | en |
dc.type | Artigo | |
dcterms.rightsHolder | Georg Thieme Verlag Kg | |
unesp.author.lattes | 2423477869556138 | |
unesp.author.orcid | 0000-0003-3829-8570[3] | |
unesp.author.orcid | 0000-0002-8637-6097[2] | |
unesp.author.orcid | 0000-0001-5367-7427[4] | |
unesp.campus | Universidade Estadual Paulista (Unesp), Faculdade de Ciências, Bauru | pt |
unesp.department | Educação Física - FC | pt |