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

Effect of aging on islet beta-cell function and its mechanisms in Wistar rats
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衰老对Wistar大鼠胰岛β细胞功能的影响及其机制

DOI:
10.1007/s11357-011-9312-7
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发表时间:
2012-12-01
期刊:
AGE
影响因子:
--
通讯作者:
Li, Chunlin
Li, Chunlin
中科院分区:
医学2区
文献类型:
--
作者:
Gu, Zhaoyan;Du, Yingzhen;Li, Chunlin

文献摘要

被引文献

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2型糖尿病的特点是胰岛β细胞功能障碍,其发病率随着年龄的增长而增加。然而,衰老对胰岛β细胞功能影响的机制尚不完全清楚。我们对 4 个月大(年轻)、14 个月大(成年)和 24 个月大(老年)雄性 Wistar 大鼠的 β 细胞功能进行了表征,发现胰岛 β 细胞功能随着年龄的增长而逐渐下降。老年大鼠表现出口服葡萄糖不耐受,并表现出葡萄糖刺激的胰岛素释放(GSIR)和棕榈酸刺激的胰岛素释放(PSIR)减少。此外,老年大鼠的总超氧化物歧化酶(T-SOD)、铜锌超氧化物歧化酶(CuZn-SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性降低,而血清丙二醛(MDA)水平升高。此外,我们发现老年组大鼠胰岛中β细胞增殖显着减少,β细胞凋亡频率增加。最后,老年大鼠胰岛中Anxa1的表达显着上调。这些数据为大鼠中与年龄相关的β细胞功能障碍的发展提供了新的见解。
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.