NAFLD对大鼠葡萄糖、胰岛素代谢和肝糖原合成的影响-东南大学学报医学版

NAFLD对大鼠葡萄糖、胰岛素代谢和肝糖原合成的影响

单位：1. 东南大学附属中大医院江北院区消化科, 江苏南京 210048;
2. 东南大学附属中大医院消化科, 江苏南京 210009

分类号：R575.5;R33-33

出版年·卷·期（页码）：2020·39·第四期（420-424）

摘要：

目的：探讨非酒精性脂肪肝（NAFLD）对大鼠葡萄糖、胰岛素代谢和肝糖原合成的影响。方法：通过高脂饮食建立NAFLD大鼠模型，穿刺肝静脉取血，检测肝脏葡萄糖、胰岛素代谢能力和糖原合成能力；蛋白质印迹法和RT-PCR检测糖原合成和糖异生相关酶基因及蛋白的表达。结果：与对照组相比，NAFLD模型组大鼠的葡萄糖、胰岛素代谢速度及肝脏糖原储备速度均显著降低，葡萄糖耐量和胰岛素耐受水平均下降，肝脏糖原合成相关酶基因和蛋白的表达水平均显著降低，肝脏糖原合成相关酶的磷酸化水平均显著降低，而糖异生相关基因的表达水平则显著升高，差异均有统计学意义（均P<0.05）。结论：NAFLD大鼠肝脏葡萄糖、胰岛素代谢能力下降，肝糖原合成减少，导致高血糖和高胰岛素血症，增加胰岛素抵抗和患2型糖尿病的危险。

Objective: To investigate the effects of non-alcoholic fatty liver disease (NAFLD) on glucose, insulin metabolism and hepatic glycogen synthesis in rats. Methods: NAFLD rat model was established by high-fat diet, blood was collected from hepatic vein, and glucose metabolism, insulin metabolism and glycogen synthesis were detected respectively. Glycogen synthesis and expression of gluconeogenesis related enzyme genes and proteins were detected by Western blotting and RT-PCR. Results: Compared with the control group, the glucose metabolism, insulin metabolic rate and liver glycogen reserve rate in NAFLD model group were significantly decreased, and the liver glycogen synthesis-related enzymes phosphorylation level was significantly decreased, however, the expression level of gluconeogenesis related genes increased significantly,the difference were all significant(all P<0.05). Conclusion: In NAFLD rats, the liver's ability to regulate glucose and insulin metabolism is decreased, liver glycogen synthesis is decreased, which results in hyperglycemia and hyperinsulinemia, and increases insulin resistance and the risk of type 2 diabetes.

参考文献：

[1] 中华医学会肝病学分会脂肪肝和酒精性肝病学组,中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南(2018年更新版)[J].临床肝胆病杂志,2018,34(5):947-957.
[2] YOUNOSSI Z,TACKE F,ARRESE M,et al.Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J].Hepatology,2019,69(6):2672-2682.
[3] KAHN S E,HULL R L,UTZSCHNEIDER K M.Mechanisms linking obesity to insulin resistance and type 2 diabetes[J].Nature,2006,444(7121):840-846.
[4] SAMUEL V T,SHULMAN G I.Mechanisms for insulin resistance:common threads and missing links[J].Cell,2012,148(5):852-871.
[5] MICHAEL M D,KULKAMRNI R N,POSTIC C,et al.Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction[J].Mol Cell,2000,6(1):87-97.
[6] SINAIKO A R,CAPPRIO S.Insulin resistance[J].J Pediatr,2012,161(1):11-15.
[7] 赖水青,洪真真,陈红梅,等.肝脏而不是骨骼肌的脂肪含量与胰岛素抵抗和糖代谢异常密切相关[J].南方医科大学学报,2017,37(11):1461-1466.
[8] LARSON-MEYER D E,NEWCOMER B R,RAVUSSIN E,et al.Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children[J].Diabetologia,2011,54(4):869-875.
[9] SEPPALA-LINDROOS A,VEHKAVAARA S,HAKKINEN AM,et al,Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men[J].J Clin Endocrinol Metab,2002,87(7):3023-3028.
[10] 袁静,朱雪萍.lncRNA-uc007gqg.1在非酒精性脂肪肝中的表达规律[J].东南大学学报(医学版),2019,38(1):6-13.
[11] 韩锦铂,王一国.肝脏糖异生的调控[J].中国细胞生物学学报,2019,41(7):1216-1224.
[12] 王汉生,李伶,杨刚毅,等.JAZF1过表达对糖异生及胰岛素信号通路的影响[J].重庆医科大学学报,2015,40(7):965-969.
[13] 李卫东,傅坤发,连燕舒,等.成人非酒精性脂肪肝与2型糖尿病发病关系的前瞻性队列研究[J].中国全科医学,2015,18(28):3426-3429.
[14] LI W D,FU K F,LI G M,et al.Comparison of effects of obesity and non-alcoholic fatty liver disease on incidence of type 2 diabetes mellitus[J].World J Gastroenterol,2015,21(32):9607-9613.
[15] TRICÒ D,CAPRIO S,UMANO G R,et al.Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents:Findings From a Multiethnic Cohort[J].Hepatology,2018,68(4):1376-1390.
[16] PANG Y,KARTSONAKI C,TUMBULL I,et al.Diabetes,plasma glucose,and Incidence of fatty liver,cirrhosis,and liver cancer:a prospective study of 0.5 million people[J].Hepatology,2018,68(4):1308-1318.
[17] MANTOVANI A,BYME C D,BONORA E,et al.Nonalcoholic fatty liver disease and risk of incident type 2 diabetes:a meta-analysis[J].Diabetes Care,2018,41(2):372-382.
[18] 李卫东,夏金荣,连燕舒.非酒精性脂肪性肝病与新诊断2型糖尿病关系的病例对照研究[J].中国全科医学,2014,17(34):4075-4082.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录