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|Type:||Artigo de periódico|
|Title:||Decreased beta-cell insulin secretory function in aged rats due to impaired Ca2+ handling|
|Author:||Ribeiro, Rosane Aparecida|
Batista, Thiago Martins
Coelho, Fernanda Monteiro
Boschero, Antonio Carlos
Lopes, Guiomar Silva
Carneiro, Everardo Magalhaes
|Abstract:||Ageing 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.|
|Appears in Collections:||IB - Artigos e Materiais de Revistas Científicas|
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