慢性应激和增龄对糖尿病易感小鼠胰岛素敏感性的影响  

Effect of chronic experimental stress on insulin sensitivity in susceptible mice to diabetes

作　　者：刘幼硕[1] 胡敏[2] 姚树桥[3] 龚耀先[3] 

机构地区：[1]中南大学湘雅二医院老年病科,长沙市410011 [2]中南大学湘雅二医院代谢内分泌研究所,长沙市410011 [3]中南大学湘雅二医院医学心理中心,长沙市410011

出　　处：《中华老年医学杂志》2005年第4期292-295,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金重点资助项目(39430070)

摘　　要：目的研究慢性应激和增龄对小剂量链脲佐菌素诱导的糖尿病易感小鼠胰岛素敏感性的影响,并从胰岛素受体水平探讨其机理。方法取15月龄(幼年)、15月龄(成年)和20月龄(老年)昆明小鼠,用小剂量链脲佐菌素多次腹腔内注射,诱导其糖尿病易感状态后,分为应激组和对照组共6组,各20只。应激组分别给予6周实验性应激源刺激(限制、旋转、拥挤),检测空腹血糖(FBG)和空腹胰岛素(FINS)水平,计算胰岛素敏感指数(ISI),用Scatchard图分析肝细胞膜胰岛素受体高、低和平均亲和常数(K1、K2和K),高、低亲和力(R1、R2),以及每mg膜蛋白胰岛素受体数目(R),用ELISA方法测定10-7mol/L胰岛素刺激的肝细胞磷酸化胰岛素受体数(PINSR)。结果经6周实验性应激,FBG水平随增龄增高,幼年组(103±62)mol/L,成年组(152±36)mol/L,老年组(189±29)mol/L(P<005);FINS水平随增龄下降,幼年组(20±6)mIU/L,成年组(13±5)mIU/L,老年组(10±7)mIU/L(P<005);应激组ISI分别较同龄对照组降低〔幼年组(-51±07)对(-46±06),成年(-50±04)对(-48±08),老年组(-56±09)对(-45±12),P<005〕;成年和老年应激组肝细胞膜R1、R2和R均较同龄对照组上升,且老年应激组较成年应激组明显升高(P均<005);各应激组PINSR均较同龄对照组下降,老年应激组下降更明显。Objective This study was to compare the effects of chronic experimental stress and aging on insulin sensitivity at insulin receptor of liver plasma membranes and its autophosphorylation in the aged mice compared with those in the young and the adult diabetes-susceptible mice. Methods Diabetes-susceptible mice was induced by streptozotocin in 40 1.5-month-old mice (young mice), 40 15-month-old mice (adult mice) and 40 20-month-old mice (aged mice). These mice were randomly divided into the stress groups and control groups, respectively. Each group contained 20 mice. Stress groups were exposed to multiple stressors (restrain, rotation, crowding) for 6 weeks. The levels of fasting blood glucose (FBG) and fasting plasma insulin (FIns) were measured. The index of insulin sensitivity (ISI) was calculated. The numbers (R_~1 , R_~2 , R) and affinity (K_~1 , K_~2 , K) of insulin receptors on liver plasma membranes were investigated by using Scatchard analysis. The numbers of insulin-stimulated (10^-7 mol/L) phosphorylated insulin receptor (PINSR) on liver plasma membranes was assayed by ELISA. Results After 6-week stress, FBG levels were significantly higher with aging 〔young mice: (10.3±6.2)mol/L, adult mice: (15.2±3.6)mol/L, aged mice: (18.9±2.9)mol/L, P<0.05〕, while FIns levels were significantly lower with aging〔young mice: (20±6) mIU/L, adult mice: (13±6)mIU/L, aged mice: (10±7) mIU/L, P<0.05〕. ISIs of all the stress groups were decreased than those of the control groups, respectively 〔young mice: (-5.1±0.7) vs ( 4.6±0.6), adult mice: (-5.0±0.4) vs ( 4.8±0.8), aged mice: (-5.6±0.9) vs ( 4.5±1.2), P<0.05〕, and the decrease in aged stress group was the most severe. Scatchard analysis showed that chronic stress had a effect of increasing the insulin receptor number (R_~1 , R_~2 , R) in the aged and adult stress mice, and the increase was more marked in the aged mice than in the adult ones (P<0.05), but no effect in the young mice. The decrease of PINSR was more marked in the aged stress mice than

关 键 词：慢性应激 增龄 糖尿病 胰岛素敏感性 

分 类 号：R587.1[医药卫生—内分泌]