艾塞那肽改善T2DM患者和db/db小鼠肝脏胰岛素抵抗的作用  

Effects of Exenatide on Hepatic Insulin Resistance in T2DM Patients and db/db Mice

作　　者：秦亚玮 李娜 黄钰涵 王晓彤 凌宏威 王涛 QIN Yawei;LI Na;HUANG Yuhan;WANG Xiaotong;LING Hongwei;WANG Tao(Department of Pharmaceuticals,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China;Department of Endocrinology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221006,China)

机构地区：[1]徐州医科大学附属医院药学部,徐州221006 [2]徐州医科大学附属医院内分泌科,徐州221006

出　　处：《药学与临床研究》2024年第2期103-108,共6页Pharmaceutical and Clinical Research

基　　金：国家自然科学基金项目(82003866);江苏省研究型医院学会-精益化用药-石药专项科研基金(JY202201);徐州市卫生健康委-彭城英才-医学青年后备人才(XWRCHT20220034)。

摘　　要：目的:探讨艾塞那肽对肝胰岛素抵抗(IR)的作用。方法:选取2017年8月~2020年8月连续使用艾塞那肽治疗6个月的80例T2DM患者,检测患者用药前后糖化血红蛋白(HbA1c)、空腹血糖(FPG)等指标,计算体质量指数(BMI)、稳态模型胰岛素抵抗指数(HOMA-IR)与稳态模型胰岛功能(HOMA-β)。以db/db小鼠为糖尿病研究模型,艾塞那肽连续治疗8周,进行葡萄糖耐受(OGTT)和胰岛素耐受(ITT)试验,测定FPG和胰岛素水平;肝脏切片进行HE和PAS染色。结果:艾塞那肽治疗后,T2DM患者HbA1c、FPG、HOMA-IR水平明显降低(P<0.05);艾塞那肽增加HepG2细胞IR模型的萄萄糖消耗量(P<0.05);艾塞那肽降低db/db小鼠FPG、空腹血清胰岛素、HOMA-IR,胰岛素敏感性增加,肝糖原累积面积增加(P<0.05)。结论:艾塞那肽可显著改善肝胰岛素抵抗。Objective:To investigate the effects of exenatide on hepatic insulin resistance(IR),which provides a strong basis for the treatment of hepatic insulin resistance in type 2 diabetes mellitus(T2DM).Methods:A total of 80 patients with T2DM that were treated with exenatide for 6 months from August 2017 to August 2020 were enrolled.Glycosylated hemoglobin(HbA1c)and fasting blood glucose(FPG)were measured before and after treatment,moreover,body mass index(BMI),homeostatic model insulin resistance index(HOMA-IR)and homeostatic model islet function(HOMA-β)were calculated.The db/db mice were treated with exenatide for 8 weeks,OGTT and ITT experiments were performed,and then fasting blood glucose and insulin levels were determined,liver sections were stained with HE and PAS.Results:After treatment of exenatide,the levels of HbA1c,FPG and HOMA-IR were significantly decreased in T2DM(P<0.05).Exenatide increased glucose consumption in IR model of HepG2 cells(P<0.05);Exenatide decreased fasting blood glucose,fasting serum insulin(FINS)and HOMA-IR in db/db mice,increased insulin sensitivity index(ISI)and liver glycogen accumulation area(P<0.05).Conclusion:Exenatide improves hepatic insulin resistance.

关 键 词：2型糖尿病 胰岛素抵抗 艾塞那肽 

分 类 号：R96[医药卫生—药理学]