Effect of aging on islet beta-cell function and its mechanisms in Wistar rats

Type 2 diabetes mellitus is characterized by islet beta-cell dysfunction and its incidence increases with age. However, the mechanisms underlying the effect of aging on islet beta-cell function are not fully understood. We characterized beta-cell function in 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats, and found that islet beta-cell function decreased gradually with age. Old rats displayed oral glucose intolerance and exhibited a decrease in glucose-stimulated insulin release (GSIR) and palmitic acid-stimulated insulin release (PSIR). Furthermore, total superoxide dismutase (T-SOD), CuZn superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activity decreased, whereas serum malondialdehyde (MDA) levels increased in the older rats. Moreover, we detected a significant reduction in beta-cell proliferation and an increase in the frequency of apoptotic beta-cells in the islets of rats in the old group. Finally, Anxa1 expression in the islets of old rats was significantly upregulated. These data provide new insights into the development of age-related beta-cell dysfunction in rats.