OLETF大鼠2型糖尿病发生发展过程中牛磺胆汁酸水平的动态变化  

Dynamic changes of taurine-conjugated bile acid levels during the development and progression of type 2 diabetes in OLETF rats

作　　者：杨笑云 常宝成[1] 韩菲[1] 张祎[1] 王翠娟[2] 孔岩[1] 张立弋 高忠爱[1] 杨菊红[1] 

机构地区：[1]天津医科大学代谢病医院内分泌研究所、卫生部激素与发育重点实验室、天津市代谢性疾病重点实验室,300070 [2]河北省秦皇岛市第一医院内分泌科 [3]天津医科大学总医院内分泌代谢科

出　　处：《中华内分泌代谢杂志》2017年第7期590-595,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目（81373864、81473472、81603461）;天津市自然科学基金重点项目（17JCZDJC34700）

摘　　要：目的 动态观察OLETF大鼠2型糖尿病发生发展过程中血清及粪中牛磺胆汁酸水平的变化,分析其与糖代谢的关系.方法 选取4周龄雄性OLETF大鼠20只,同时选取同周龄的雄性LETO大鼠10只作为正常对照组.适应性喂养后用高脂饲料喂养OLETF大鼠,用普通饲料喂养LETO大鼠.观察OLETF大鼠基线时、正常糖耐量、糖耐量受损及糖尿病阶段血、粪牛磺酸胆汁酸水平的变化及其与糖代谢、糖调节激素水平的关系.结果 与LETO对照大鼠相比, OLETF大鼠基线血牛磺胆汁酸无明显变化,但粪牛磺胆汁酸包括牛磺鹅脱氧胆酸（TCDCA）、牛磺胆酸（TCA）及牛磺脱氧胆酸（TDCA）均明显下降[（14.25±7.18对0.90±0.31）mg/kg、（7.12±4.14对1.30±0.35）mg/kg、（4.30±1.78对1.02±0.14）mg/kg,均P〈0.01],且在糖尿病发生发展过程中,以上3种牛磺胆汁酸始终低于同周龄正常对照大鼠.相关分析发现血TCDCA、TDCA与体重及空腹血糖明显负相关;粪TDCA与空腹血糖明显负相关（r=-0.470,P=0.032）,与血清胰升糖素样肽1（GLP-1）水平明显正相关（r=0.406,P=0.044）.结论 肠道牛磺胆汁酸水平下降参与了OLETF大鼠糖尿病的发生发展.肠道TDCA可能通过旁分泌途径促进GLP-1分泌.Objective To observe the changes of serum and fecal taurine-conjugated bile acid levels and its association with glucose metabolism during the spontaneous development of type 2 diabetes in OLETO rats.Methods Twenty male OLETF rats（4 weeks old）were included and 10 male LETO rats of the same age were used as the normal control group.OLETF rats were fed with high fat diet whereas LETO rats were fed with normal diet.Serum and fecal taurine-conjugated bile acid levels of OLETF rats were tested at different stage of diabetes including baseline, normal glucose tolerance, impaired glucose tolerance and diabetes periods, and the association of taurine-conjugated bile acid level with body weight, blood glucose, and glucose-regulating hormones were also investigated.Results Compared with LETO rats, the baseline serum levels of taurine-conjugated bile acid in OLETF rats did not change, but the levels of fecal taurine-conjugated bile acid including taurine-conjugated chenodeoxycholic acid（TCDCA）, taurocholic acid（TCA）and taurine-conjugated deoxycholic acid（TDCA）were significantly decreased [（14.25±7.18 vs 0.90±0.31）mg/kg,（7.12±4.14 vs 1.30±0.35）mg/kg,（4.30±1.78 vs 1.02±0.14）mg/kg, all P〈0.01].During the development of diabetes, the fecal levels of TCDCA, TCA and TDCA were still lower than those in the control rats.TDCA was negatively associated with the level of fasting blood glucose（r=-0.470, P=0.032）,but positively associated with the serum level of glucagon-like peptide（GLP）-l（r=0.406, P=0.044）.Conclusion The decrease of intestinal taurine-conjugated bile acid level is involved in the development of diabetes in OLETF rats.Intestinal TDCA may regulate the secretion of GLP-1 by paracrine pathway.

关 键 词：牛磺胆汁酸 糖尿病  2型 胰升糖素样肽1 牛磺脱氧胆酸 

分 类 号：R587.1[医药卫生—内分泌]