Decreased beta-cell insulin secretory function in aged rats due to impaired Ca2+ handling

dc.creatorRibeiro, Rosane Aparecida
dc.creatorBatista, Thiago Martins
dc.creatorCoelho, Fernanda Monteiro
dc.creatorBoschero, Antonio Carlos
dc.creatorLopes, Guiomar Silva
dc.creatorCarneiro, Everardo Magalhaes
dc.date2012
dc.date2013-09-19T18:05:57Z
dc.date2016-07-01T14:52:00Z
dc.date2013-09-19T18:05:57Z
dc.date2016-07-01T14:52:00Z
dc.date.accessioned2018-03-29T01:54:52Z
dc.date.available2018-03-29T01:54:52Z
dc.identifierExperimental Physiology. Wiley-Blackwell, v.97, n.9, p.1065-1073, 2012
dc.identifier0958-0670
dc.identifierWOS:000308047000008
dc.identifier10.1113/expphysiol.2012.064790
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/1849
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/1849
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1308655
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionAgeing is associated with an increased impairment in glucose homeostasis and an increased incidence of type 2 diabetes. In this study, we evaluated beta-cell function and its implications for glucose homeostasis in 24-month-old female Wistar rats. Aged rats showed lower plasma glucose levels in the fed and fasting states compared with control rats. In addition, insulinaemia in the fed state was reduced in the older rats. Insulin receptor beta (IR beta) expression was lower in the livers of the aged animals, whereas IR beta and Akt1/2/3 protein expressions were higher in the muscles. These effects may contribute to the normal glucose tolerance observed in older rodents. Isolated islets from aged rats secreted less insulin in response to 8.3 and 16.7 mm glucose. Accordingly, this group presented a lower [Ca2+]i in the presence of glucose and a depolarizing stimulus (30 mm K+). In addition, islets from aged rats showed reduced insulin secretion in response to 100 mu m carbachol (CCh), 10 nm phorbol 12-myristate 13-acetate and 10 mu m forskolin. The expressions of protein kinase C, protein kinase A and exocytotic proteins, such as syntaxin 1 and synaptosomal-associated protein 25 kDa (SNAP-25), were similar in islets from aged and control rats. In conclusion, our evidence suggests that the increased incidence of type 2 diabetes with age may be due to a progressive decline in beta-cell secretory capacity due to disruption of Ca2+ handling. Furthermore, the expression of proteins of the insulin transduction cascade showed an adaptive profile, with a compensatory increase in IR beta and Akt1/2/3 in gastrocnemius muscles, which may maintain normal glucose homeostasis in 24-month-old rats.
dc.description97
dc.description9
dc.description1065
dc.description1073
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherWiley-Blackwell
dc.publisherHoboken
dc.relationExperimental Physiology
dc.rightsfechado
dc.sourceWOS
dc.subjectPANCREATIC-ISLETS
dc.subjectGLUCOSE-TOLERANCE
dc.subjectDIABETES-MELLITUS
dc.subjectUS POPULATION
dc.subjectOLD-AGE
dc.subjectPROTEIN
dc.subjectSENSITIVITY
dc.subjectEXPRESSION
dc.subjectRESISTANCE
dc.subjectAPOPTOSIS
dc.titleDecreased beta-cell insulin secretory function in aged rats due to impaired Ca2+ handling
dc.typeArtículos de revistas


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