title: Decreased β-cell insulin secretory function in aged rats due to impaired Ca(2+) handling.
abstract: Ageing is associated with an increased impairment in glucose homeostasis and an increased incidence of type 2 diabetes. In this study, we evaluated β-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 β (IRβ) expression was lower in the livers of the aged animals, whereas IRβ and Akt(1/2/3) 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 [Ca(2+)](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 μm carbachol (CCh), 10 nm phorbol 12-myristate 13-acetate and 10 μm 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 β-cell secretory capacity due to disruption of Ca(2+) handling. Furthermore, the expression of proteins of the insulin transduction cascade showed an adaptive profile, with a compensatory increase in IRβ and Akt(1/2/3) in gastrocnemius muscles, which may maintain normal glucose homeostasis in 24-month-old rats.
authors.affiliation: Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil. rosaneribeirobio@yahoo.com.br
authors.forename: Rosane Aparecida
authors.initials: RA
authors.lastname: Ribeiro
authors.forename: Thiago Martins
authors.initials: TM
authors.lastname: Batista
authors.forename: Fernanda Monteiro
authors.initials: FM
authors.lastname: Coelho
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
authors.forename: Guiomar Silva
authors.initials: GS
authors.lastname: Lopes
authors.forename: Everardo Magalhães
authors.initials: EM
authors.lastname: Carneiro
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D005215:Fasting / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D050825:Synaptosomal-Associated Protein 25; D002217:Carbachol; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose; D002118:Calcium