增龄对Wistar大鼠胰岛b细胞胰岛素受体的影响
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Effect of aging on insulin receptor in islet beta-cells of Wistar rats
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    摘要:

    目的 观察增龄对大鼠胰岛β细胞胰岛素受体的影响, 探讨老年糖耐量受损的机制。方法 将Wistar大鼠30只分为青年组(15只)和老年组(15只), 观察空腹血糖、空腹胰岛素、血清游离脂肪酸(FFA)、血脂的变化, 同时进行高胰岛素-正葡萄糖钳夹实验观察胰岛素敏感性。两组大鼠胰腺石蜡切片, 免疫荧光双标染色, 标染胰岛β细胞上胰岛素受体, 利用软件进行荧光强度分析。结果 青年组和老年组的大鼠体重分别为(490.6±7.72)g和(728.9±7.57)g, 有明显统计学意义(P<0.01); 两组大鼠空腹血糖无明显差异, 空腹胰岛素青年组为(0.59±0.14)ng/ml, 老年组为(2.37±0.04)ng/ml, 差异有统计学意义(P<0.01); 空腹血清FFA水平青年组为(0.76±0.14)mmol/L, 老年组为(1.51± 0.04)mmol/L, 有统计学差异(P<0.01); 高胰岛素-正葡萄糖钳夹结果显示青年组大鼠葡萄糖输出速率为(26.02± 2.83)mg/(kg?min), 老年组为(10.73±0.72)mg/(kg?min), 差异有统计学意义(P<0.01); 使用稳态模型评估胰岛素分泌指数(HOMA-β)随年龄增长呈递增趋势, 未达到统计学差异; 而胰岛素抵抗指数(HOMA-IR)在青年组和老年组分别为3.09±0.80和13.14±l.59, 差异有统计学意义(P<0.01); 免疫荧光染色显示老年组胰岛β细胞上胰岛素受体荧光强度减弱, 荧光强度分析值青年组为63.55±5.20、老年组为23.26±2.50, 差异有统计学意义(P<0.01)。结论 随着年龄的增长, 老年大鼠存在一定的胰岛素抵抗和代偿性胰岛素分泌增加, 同时胰岛β细胞胰岛素受体减少, 可能存在胰岛β细胞自身胰岛素抵抗。

    Abstract:

    Objective To evaluate the effect of aging on the insulin receptor in islet beta-cells of Wistar rats, so as to investigate the mechanism of impaired glucose tolerance in elderly population. Methods Thirty healthy male Wistar rats were divided into young group(4-month old, n = 15) and elderly group(24-month old, n = 15). The fasting blood glucose, blood insulin, free fatty acid, and blood lipid were observed. Insulin sensitivity and the function of islet cells were assessed by the euglycaemic-hyperinsulinaemic clamp technique. The insulin receptor in islet beta-cells was observed using immunofluorescence staining, and the fluorescence intensity was analyzed using software. Results The body mass of rats in young group and elderly group was (490.60±7.72)g and (728.90±7.57) g respectively(P<0.01). There was no significant difference in fasting blood glucose between the two groups(P>0.05). The fasting blood insulin was (0.59±0.14)ng/ml and (2.37±0.04)ng/ml in young group and elderly group respectively (P<0.01). The blood free fatty acid was significantly lower in young group than in elderly group[(0.76±0.14) vs (1.51±0.04) mmol/L,P<0.01]. The euglycaemic-hyperinsulinaemic clamp test displayed that the glucose infusion rate was significantly higher in young group than in elderly group[( 26.02±2.83) vs (10.73±0.72)mg/(kg?min),P<0.01]. Homeostasis model insulin resistance index(HOMA-IR) was (3.09±0.80) and (13.14±l.59) in young group and elderly group(P<0.01). The fluorescence intensity was (63.55±5.20) and (23.26±2.50) respectively in young group and elderly group respectively(P<0.01). Conclusion The elderly rats present with insulin resistance and compensatory high level insulin secretion. Meanwhile, insulin receptor in islet beta-cells is decreased. It is possible that the peripheral insulin resistance and the insulin resistance in islet beta-cells itself coexist in elderly rats.

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马丽超, 谷昭艳, 杜英臻, 等.增龄对Wistar大鼠胰岛b细胞胰岛素受体的影响[J].中华老年多器官疾病杂志,2011,10(4):310~314

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