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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,幼年组13±
Objective To investigate the effects of chronic stress and aging on the insulin sensitivity in diabetic mice sensitive to low-dose streptozotocin (STZ-induced) and to explore its mechanism from the insulin receptor level. Methods Kunming mice (15 months old, 15 months old and 20 months old) were injected intraperitoneally with low dose of streptozotocin to induce their susceptibility to diabetes. There were 6 stress groups and 20 control groups. Stress group were given 6 weeks of experimental stress stimulation (limit, rotation, crowding), fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured to calculate the insulin sensitivity index (ISI), Scatchard chart analysis of liver cell membrane insulin Low and average affinity constants (K1, K2 and K), high and low affinity (R1, R2) and the number of insulin receptors per mg of membrane protein (R) were determined by ELISA using 10-7 mol / L Insulin-stimulated hepatocyte phosphorylated insulin receptor count (PINSR). Results After 6 weeks of experimental stress, the level of FBG increased with age in young group (103 ± 62) mol / L, in adult group (152 ± 36) mol / L, and in elderly group (189 ± 29) mol / L (20 ± 6) mIU / L, (13 ± 5) mIU / L in adult group and (10 ± 7) mIU / L in elderly group (P <005). The level of FINS decreased with aging Compared with the same age control group, the ISI of the experimental group was significantly lower than that of the control group of the same age (-46 ± 06, -50 ± 04, -48 ± 08, -56 ± 09, (-45 ± 12), P <005]. The levels of R1, R2 and R in liver cell membrane of adults and senile stress group were higher than that of the same age control group, and the senile stress group was significantly higher than that of adult stress group (all P < ); The PINSR in each stress group decreased compared with the control group of the same age, and the depression in the aged stress group was more obvious. In the juvenile group, 13 ±