达格列净干预不同时长对2型糖尿病小鼠胰岛β细胞保护作用的研究  

Protective effect of different durations of dapagliflozin treatment on pancreaticβ-cells in type 2 diabetic mice

作　　者：王丹丹[1] 杨琨[1] 杨进[1] 洪天配[1] 魏蕊[1] Wang Dandan;Yang Kun;Yang Jin;Hong Tianpei;Wei Rui(Department of Endocrinology and Metabolism,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院内分泌科,北京100191

出　　处：《中华糖尿病杂志》2023年第9期828-834,共7页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家自然科学基金(81830022,81970671,82271611)。

摘　　要：目的探讨达格列净干预不同时长对db/db小鼠胰岛β细胞功能和形态学的影响。方法20只13周龄雄性db/db小鼠分为4组,分别给予达格列净(1 mg/kg)或溶媒(水)每日灌胃干预6或12周,即对照干预6周组、达格列净干预6周组、对照干预12周组和达格列净干预12周组,每组5只小鼠。检测小鼠体重、空腹血糖、口服葡萄糖耐量试验血糖、空腹血浆胰岛素水平等代谢指标。采用免疫荧光染色分析β细胞面积及其占比。组间比较采用独立样本t检验。结果与各自对照组相比,不同时长的达格列净干预组小鼠体重差异均无统计学意义(P>0.05),但空腹血糖和口服葡萄糖耐量负荷后血糖水平均显著降低(P<0.05),且达格列净干预12周组比达格列净干预6周组效果更显著。与对照干预12周组相比,达格列净干预12周组显著升高空腹血浆胰岛素水平[分别为(21.60±2.76)和(7.03±1.80)ng/ml,P=0.004],但达格列净干预6周组则未见该效应。免疫荧光染色分析显示,与对照组相比,达格列净干预12周组显著增加β细胞面积[分别为(14554.5±1426.5)和(11165.0±379.8)μm^(2),P<0.05]和β细胞面积/胰腺面积比值(分别为0.27‰±0.04‰和0.15‰±0.02‰,P<0.05),而达格列净干预6周组则差异未见统计学意义(P>0.05)。结论不同时长达格列净干预均可降低db/db小鼠血糖,但长时间达格列净干预的降糖作用更好,并且可改善β细胞功能和增加β细胞总量。Objective To investigate the effect of treatment with dapagliflozin for different durations on pancreatic isletβ-cell function and morphology in db/db mice.Methods Twenty male db/db mice(13-week-old)were randomly divided into four groups,and treated with dapagliflozin(1 mg/kg)or vehicle(water)via gavage daily for 6 or 12 weeks.The four groups were as follows:6-week control treatment group,6-week dapagliflozin treatment group,12-week control treatment group and 12-week dapagliflozin treatment group,5 mice in each group.Metabolic parameters,including body weight,fasting plasma glucose,oral glucose tolerance test(OGTT)and fasting plasma insulin levels were assessed.β-cell area andβ-cell area/pancreatic area ratio were analyzed by using immunofluorescent quantification.Independent samples t-test was used for comparison between groups.ResultsDifferent durations of dapagliflozin treatment had no significant effect on body weight when compared to the respective control group.Notably,dapagliflozin treatment significantly reduced the fasting blood glucose levels and post-load blood glucose levels during OGTT,with greater effects in the 12-week dapagliflozin treatment group than in the 6-week dapagliflozin treatment group.Meanwhile,the 12-week dapagliflozin treatment group significantly upregulated the fasting plasma insulin levels[(21.60±2.76)vs.(7.03±1.80)ng/ml,P=0.004],whereas the 6-week dapagliflozin treatment group did not show such an effect.Pancreatic immunofluorescent analysis showed that,compared with the control group,the 12-week dapagliflozin treatment group significantly increased theβ-cell area[(14554.5±1426.5)vs.(11165.0±379.8)μm^(2),P<0.05]and theβ-cell area/pancreatic area ratio(0.27‰±0.04‰vs.0.15‰±0.02‰,P<0.05),whereas the 6-week dapagliflozin treatment group did not have these effects(P>0.05).Conclusions Both 6-week and l2-week treatment with dapagliflozin can lower the blood glucose levels in db/db mice.However,the long-term treatment shows more pronounced effects on glucose control a

关 键 词：糖尿病 2型 胰岛 Β细胞 达格列净 胰岛形态 

分 类 号：R965[医药卫生—药理学]