生酮饮食改善db/db小鼠胰岛β细胞去分化  

Ketogenic diet improves pancreaticβ-cell dedifferentiation in db/db mice

作　　者：张梦潇 韦晓[1] 孙烁烁 张少红 陈国芳[1] 刘超[1] Zhang Mengxiao;Wei Xiao;Sun Shuoshuo;Zhang Shaohong;Chen Guofang;Liu Chao(Department of Endocrinology,Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Jiangsu Provincial Academy of Traditional Chinese Medicine;Key Laboratory of Physic Diseases and Treatment of State Administration of Traditional Chinese Medicine,Nanjing 210028,China)

机构地区：[1]南京中医药大学附属中西医结合医院内分泌科,江苏省中医药研究院,国家中医药管理局瘿病证治重点研究室,210028 [2]南京中医药大学附属盐城市中医院老年病科,224000

出　　处：《中华内分泌代谢杂志》2022年第2期144-150,共7页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81800756);江苏省六大人才高峰(WSN-035)。

摘　　要：目的研究生酮饮食(KD)对db/db小鼠胰岛β细胞去分化的影响。方法选用8周龄2型糖尿病小鼠模型db/db雄性小鼠,适应性喂养3周后,分为正常喂养组(ND)、生酮饮食组(KD)、75%热量限制组(CR),另将8周龄C57BL/6雄性小鼠作为正常对照组(C),以标准饲料喂养。C、ND组自由进食标准饲料,KD组自由进食生酮饲料,CR组作为阳性对照组,每日以ND组75%的热量进食标准饲料。不同饮食干预4周后,检测各组小鼠体重、空腹血糖、空腹胰岛素、糖耐量及血β-羟丁酸水平;苏木精-伊红染色观察小鼠胰腺组织内胰岛的形态和结构;免疫荧光共染观察小鼠胰岛β细胞特异性转录因子的表达。结果饮食干预4周后,与ND组相比,KD组小鼠空腹血糖、胰岛素和葡萄糖曲线下面积显著降低(P<0.05);KD组胰岛形态和结构较规整,胰岛细胞数量增加;胰腺免疫荧光共染显示KD恢复胰岛β细胞的数量和排列及胰岛β/α细胞比例,恢复胰腺十二指肠同源盒-1等β细胞特异性转录因子的表达。结论KD可降低db/db小鼠的空腹血糖和胰岛素,改善糖耐量,可能与其能够恢复β细胞特异性转录因子的表达,逆转胰岛β细胞去(转)分化有关。Objective To evaluate the effects of ketogenic diet(KD)on pancreaticβ-cell dedifferentiation in db/db mice.Methods In animal study,8-week-old db/db male mice with type 2 diabetes mellitus(T2DM)were randomly divided into 3 groups:T2DM model group(ND),KD group,75%caloric restriction(CR)group,and male C57BL/6 mice of the same age as normal control group(C)fed with standard diet.Both C and ND groups were on ad lititum feeding of chow,the KD group was free to eat the ketogenic diet,and the CR group was the positive control group,consuming 75%of the calories of the ND group every day.Four weeks after different diet intervention,body weight,fasting blood glucose,fasting insulin,glucose tolerance and bloodβ-hydroxybutyric acid(BHB)were measured.Morphology and structure of pancreatic islet was observed by hematoxylin-eosin staining(HE).Immunofluorescence co-staining was used to observe the expression of mouse pancreaticβ-cell specific transcription factors.Results After 4 weeks diet intervention,the fasting blood glucose,insulin and the area under the curve of blood glucose in KD group was significantly decreased(P<0.05);When compared with ND group,the morphology and structure of the islets in the KD group were more regular,and the number of islet cells increased as revealed with HE staining.Pancreatic immunofluorescence co-assay showed that KD not only restored the number and arrangement ofβ-cells and the ratio ofβ/α-cell in the pancreatic islets,but also reversed the expression of specificβ-cell transcription factors such as pancreatic duodenal homeobox factor-1(PDX1).Conclusion KD can reduce fasting blood glucose,fasting insulin and improve glucose tolerance in db/db mice,which may be related to its ability to restore the expression of specificβ-cell transcription factors and reverse the dedifferentiation of pancreaticβ-cells.

关 键 词：糖尿病 2型 生酮饮食 胰岛Β细胞 去分化 

分 类 号：R587.1[医药卫生—内分泌]