Wang Shuang, Li Jun, Li Xiu-Jun
Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2008 Mar;39(2):197-201.
To evaluate the effect of aging on metabolic profile and the changes in morphology and secreting function of beta-cell.
SD rats with different ages (5-6, 11-12, 20-24 Mon.) were used in this experiment to detect fasting blood glucose, lipid profile and free fatty acids (FFA) as metabolic parameters. Islet population and beta-cell shape from different age groups were assessed by immunohistochemistry and electron microscope (EM), respectively. Moreover, isolated rat islets from different ages were purified and cultured with two culture medium containing 5. 6 mmol/L and 16.7 mmol/L glucose over 24 hours, respectively. The secreted levels of insulin at 2, 4, 6, 24 hours were measured by radioimmunoassay (RIA).
(1) The significantly higher concentration of FFA was found in 11-12, 20-24 months groups (386.02+/-88.08; 349.43+/-93.47 vs. 263.93+/-68.77 mmol/L, respectively, P<0.05), with no difference in WT, FBG, lipid profile among three groups; (2) Insulin secretion by glucose (5.5 mmol/L) stimulating old rats showed lower peak value than younger counterparts did [6.40+/-2.7 vs. 13.97+/-1.23 (6 Mon.) & 12.08+/-0.76 (12 Mon.) mU/L x 30 islets] and so did another glucose (16.7 mmol/L) group [6.75+/-4.69 vs. 13.41+/-0.72 (6 Mon.) & 13.56+/-0.60 (12 Mon.)]. (3) The ratio of beta-cell mass to islet was slightly larger in old rats than in younger rats (72.99+/-29.65% vs. 67.76+/-23.48% (12 Mon.) & 61.69+/-30.12% (6 Mon.), P>0.05); The expression of insulin measured by immunohistochemistry was dramatically decreased in old rat islet compared with 5-6, 11-12 month rats [242.71+/-95.37 (24 Mon.), 309+/-83.99 (12 Mon.) vs. 558+/-69.94 (6 Mon.), P<0.05].
Older rats showed higher FFA and age-related impairment of insulin secretion with or without the glucose stimulation. These findings suggest that insulin therapy should be taken into account for elder earlier once type 2 diabetes is diagnosed.
评估衰老对代谢谱以及β细胞形态和分泌功能变化的影响。
本实验使用不同年龄(5 - 6、11 - 12、20 - 24月龄)的SD大鼠,检测空腹血糖、血脂谱和游离脂肪酸(FFA)作为代谢参数。分别通过免疫组织化学和电子显微镜(EM)评估不同年龄组的胰岛数量和β细胞形态。此外,将不同年龄的大鼠分离胰岛进行纯化,并分别在含5.6 mmol/L和16.7 mmol/L葡萄糖的两种培养基中培养24小时。通过放射免疫分析法(RIA)测定2、4、6、24小时胰岛素分泌水平。
(1)在11 - 12、20 - 24月龄组中发现FFA浓度显著更高(分别为386.02±88.08;349.43±93.47 vs. 263.93±68.77 mmol/L,P<0.05),三组间的体重、空腹血糖、血脂谱无差异;(2)葡萄糖(5.5 mmol/L)刺激老龄大鼠胰岛素分泌的峰值低于年轻大鼠[6.40±2.7 vs. 13.97±1.23(6月龄)和12.08±0.76(12月龄)mU/L×30个胰岛],另一个葡萄糖(16.7 mmol/L)组也是如此[6.75±4.69 vs. 13.41±0.72(6月龄)和13.56±0.60(12月龄)]。(3)老龄大鼠β细胞质量与胰岛的比例略大于年轻大鼠(72.99±29.65% vs. 67.76±23.48%(12月龄)和61.69±30.12%(6月龄),P>0.05);通过免疫组织化学测定,老龄大鼠胰岛中胰岛素的表达与5 - 6、11 - 12月龄大鼠相比显著降低[242.71±95.37(24月龄),309±83.99(12月龄)vs. 558±69.94(6月龄),P<0.05]。
老龄大鼠无论有无葡萄糖刺激均表现出较高的FFA以及与年龄相关的胰岛素分泌受损。这些发现表明,一旦诊断为2型糖尿病,应尽早考虑对老年人进行胰岛素治疗。