初发2型糖尿病患者磷酸西格列汀干预后端粒长度及端粒酶活性变化

Changes of leukocyte telomere length and telomerase activity after intervention of sitagliptin in initial type 2 diabetes

目的:本研究检测2型糖尿病患者外周白细胞中端粒长度及端粒酶活性,并运用降糖药磷酸西格列汀干预2个月,分析其与年龄、病程、胰岛素抵抗、血糖控制水平的相关性,探讨磷酸西格列汀对初发糖尿病患者B细胞保护的可能机制。方法:以41例正常对照组(control,CTL)和32例初发糖尿病患者组(type 2diabetes,T2D)为研究对象,葡萄糖氧化酶法检测空腹静脉血糖(fasting plasma glucose,FPG),电化学发光法检测空腹静脉胰岛素水平(fasting insulin,FIN),测量体重指数(bodymass index,BMI),根据FPG及FIN评估胰岛素抵抗程度(HOMA-IR)。提取研究对象外周白细胞,southernblots法检测细胞内端粒长度,TRAP-ELISA检测端粒酶活性。结果:2组研究对象年龄、性别、BMI具可比性。T2D组端粒长度较CTL组明显减短,端粒酶活性变化不显著。T2D组中相关分析结果显示,端粒长度与年龄显著相关。经2个月的磷酸西格列汀干预后,端粒长度逐渐增加,而端粒酶活性仍无显著改变。结论:初发糖尿病中,磷酸西格列汀可能是通过改善减短的端粒长度来保护B细胞。

OBJECTIVE To determine whether telomeric shortening changes after intervention by sitagliptin for two months in initial type 2 diabetic patients, and the possibility mechanism that sitagliptin acted on B cell in pancreases through te[omere extending. METHODS Type 2 diabetic patients （n = 32） and age- and sex- matched control nomdiabetic subjects （n = 41 ） were selected from the department of outpatient of Tongji Hospital, Tongji Medical College, Huazhong university of Science and Technology. Using Southern blot analysis, the mean terminal restriction fragment （TRF） length,a measure of average telomere size, in leukocyte DNA was determined. The activities of telomerase were measured by TRAP-ELISA method. Peripheral insulin resistance （homeostasis model assessment） was calculated from FPG and FIN. RESULTS TRF lengths of the type 2 diabetic patients （T2D） （1.6 ＋ 0. 6） were significantly shorter than those of control subjects （CTL） （4. 0 ＋ 0. 9）. Among the biochemi cal parameters,only levels o[ age were negatively correlated with shortened telomeres in T2D subiects. No decreasing of activi ties of telomerase was found before and after intervention by sitagliptin, but shorten TRF lengths were prolonged after interven tion. CONCLUSION Sitagliptin might protect B cell in pancreases by improving the length of the shortened telomere in initial type 2 diabetes.