DOI: 10.3724/SP.J.1264.2011.00005

Chinese Journal of Multiple Organ Diseases in the Elderly (中华老年多器官疾病杂志) 2011/10:4 PP.310-314

Effect of aging on insulin receptor in islet beta-cells of Wistar rats

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.

Key words:aging,insulin resistance,euglycaemic-hyperinsulinaemic clamp,insulin receptor

ReleaseDate:2014-07-21 15:56:17

[1] Escrivá F, Gavete ML, Fermín Y, et al. Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: role of adiposity[J]. J Endocrinol, 2007, 194(1): 131-141.

[2] Donati A, Recchia G, Cavallini G, et al. Effect of aging and anti-aging caloric restriction on the endocrine regulation of rat liver autophagy[J]. J Gerontol A Biol Sci Med Sci, 2008, 63(6): 550-555.

[3] Catalano KJ, Bergman RN, Ader M. Increased susceptibility to insulin resistance associated with abdominal obesity in aging rats[J]. Obes Res 2005, 13(1): 11-20.

[4] 谷昭艳, 杜英臻, 李春霖, 等. 增龄对大鼠胰岛β细胞功能的影响[J]. 中华老年多器官疾病杂志, 2009, 8(2): 166-169.

[5] 贾伟平, 陈 蕾, 项坤三, 等.扩展高胰岛素-正葡萄糖钳夹技术的建立[J]. 中华内分泌代谢杂志, 2001, 17(5): 268-271.

[6] Wilson PW, Anderson KM, Kannel WB. Epidemiology of diabetes mellitus in the elderly. The Framingham Study[J]. Am J Med, 1986, 80(5A): 3-9.

[7] 崔美芝, 刘 浩, 李春艳. 衰老动物模型的建立及评价[J]. 中国比较医学杂志, 2006, 16(2): 118-121.

[8] Guerre-Millo M.Adipose tissue and adipokines: for better or worse[J].Diabetes Metab, 2004, 30(1): 13-19.

[9] Kershaw EE, Flier JS. Adipose tissue as an endocrine organ[J]. J Clin Endocrinol Metab, 2004, 89(6): 2548-2556.

[10] Slawik M, Vidal-Puig AJ. Lipotoxicity, overnutrition and energy metabolism in aging[J]. Ageing Res Rev, 2006, 5(2): 144-164.

[11] Ahrén B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies[J]. Eur J Endocrinol, 2004, 150(2): 97-104.

[12] Kulkarni RN, Brüning JC, Winnay JN, et al. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes[J]. Cell, 1999, 96(3): 329-339.

[13] 邬云红, 李秀钧, 李宏亮, 等. 高脂饮食肥胖大鼠胰岛细胞胰岛素抵抗机理的探讨[J]. 中华医学杂志, 2005, 85(25): 1907-1910.

[14] Leibiger IB, Leibiger B, Moede T, et al.Exocytosis of insulin promotes insulin gene transcription via the insulin receptor/PI-3 kinase/p70 s6 kinase and CaM kinase pathways[J]. Mol Cell, 1998, 1(6): 933-938.