西格列汀对脂多糖诱导胰岛β细胞数量与功能改变的影响  

Effect of sitagliptin on lipopolysaccharide-induced changes in the mass and function of islet β cells

作　　者：胡星云[1] 刘珊英[2] 刘晓丹[1] 蒋清凌 严励[1] 李焱[1] 

机构地区：[1]中山大学孙逸仙纪念医院内分泌科,广州510120 [2]中山大学孙逸仙纪念医院林百欣医学研究中心

出　　处：《中华内分泌代谢杂志》2015年第5期447-451,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（81070598）;2012年中华医学会临床医学科研专项资金（12020620362）

摘　　要：目的探讨二肽基肽酶IV（DPP-4）抑制剂对脂多糖诱导的胰岛β细胞数量与功能改变的影响。方法不同浓度西格列汀（Sitagliptin）与脂多糖处理RINm细胞24h后，采用CCK-8比色法检测细胞增殖，Annexinv／PI染色流式细胞术检测细胞凋亡，ELISA法检测细胞胰岛素分泌功能，RT-PCR检测白细胞介素6（IL-6）mRNA表达。结果脂多糖组较对照组明显促进RINm细胞的增殖（0．89±0．04对1．14±0．08，P〈0．01），但脂多糖＋西格列汀各组与脂多糖组相比差异均无统计学意义；脂多糖＋10^-1mmol／L西格列汀组凋亡率较脂多糖组明显减低；各组之间胰岛素基础分泌量无明显差异，但高糖／低糖刺激后，脂多糖组较对照组胰岛素分泌量增加：脂多糖＋西格列汀组IL-6mRNA表达较脂多糖组明显减低（0．77±0．33对1．30±0．41，P=0．006）。结论DPP-4抑制剂对脂多糖诱导β细胞增殖的影响较弱，但一定程度上能够抑制脂多糖对B细胞促凋亡及胰岛素分泌功能的作用，这可能与炎症因子IL-6的表达有关。Objective To investigate the effect of dipeptidyl peptidase-4 （DPP-4） inhibitor on lipopolysaccharide （LPS） -induced changes in the mass and function of pancreatic β-cells. Methods RINm cells were cultured and treated with LPS alone or combined with different concentrations of sitagliptin for 24 h. The proliferation of RINm cells was detected by CCK-8 assay. Apoptotic rate was determined by Annexin V-fluorescein isothiocyanate （FITC）/propidium iodide flow cytometry. Insulin secretion was measured by enzyme-linked immunosorbent assay. The expression of IL-6 mRNA was displayed by RT-PCR. Results LPS significantly stimulated the proliferation of RINm cells （0.89 ± 0.04 vs 1.14 ± 0.08, P〈0.01 ）, while LPS＋sitagliptin showed no significant difference compared with LPS group. The cell apoptotic rate in LPS ± 10-1 mmol/L sitagliptin group was significantly lower than that in LPS group. There were no significant differences in basal insulin secretion among all groups, but after the high/low glucose stimulation, LPS increased insulin secretion as compared with the control. The IL-6 mRNA expression in LPS＋sitagliptin group was significantly lower than that in LPS group （0.77 ±0.33 vs 1.30 ± 0.41, P = 0. 006 ）. Conclusions DPP-4 inhibitor has no influence on LPS-induced proliferation of pancreatic β-cell, but it can inhibit LPS-induced apoptosis and insulin secretion, and IL-6 may be involved in the process.

关 键 词：二肽基肽酶Ⅳ抑制剂 脂多糖 胰岛Β细胞 

分 类 号：R587.1[医药卫生—内分泌]