[1]马玉梅,傅松波,金生禄,等.GLP-1类似物改善糖尿病大鼠胰岛素敏感性的研究[J].国际内分泌代谢杂志,2021,41(04):313-317.[doi:10.3760/cma.j.cn121383-20210313-03033]
　Ma Yumei,Fu Songbo,Jin Shenglu,et al.Glucagon-like peptide-1 analogue improves insulin sensitivity in diabetic rats[J].International Journal of Endocrinology and Metabolism,2021,41(04):313-317.[doi:10.3760/cma.j.cn121383-20210313-03033]
点击复制

GLP-1类似物改善糖尿病大鼠胰岛素敏感性的研究()
分享到：

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
41
期数:
2021年04期
页码:
313-317
栏目:
论著
出版日期:
2021-07-20

文章信息/Info

Title:
Glucagon-like peptide-1 analogue improves insulin sensitivity in diabetic rats
作者:
马玉梅1; 傅松波2; 金生禄1; 来秀娟1; 蔡秀梅1; 马承旭2; 马小妮2; 赵楠2;  井高静2
1兰州市七里河区人民医院内科 730050; 2兰州大学第一医院内分泌科 730000
Author(s):
Ma Yumei1;  Fu Songbo2;  Jin Shenglu1;  Lai Xiujuan1;  Cai Xiumei1;  Ma Chengxu2;  Ma Xiaoni2;  Zhao Nan2;  Jing Gaojing2.
1Department of Internal Medicine, Qilihe District People's Hospital of Lanzhou City, Lanzhou 730050, China; 2Department of Endocrinology, the First Hospital of Lanzhou University, Lanzhou 730000, China
关键词:
胰高血糖素样肽受体激动剂;  糖尿病;  胰岛素抵抗;  自噬
Keywords:
glucagon-like peptide-1 receptor agonist;  Diabetes mellitus;  Insulin resistance;  Autophagy
DOI:
10.3760/cma.j.cn121383-20210313-03033
摘要:
目的 探讨胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽改善糖尿病大鼠胰岛素敏感性的可能机制。方法 雄性Wistar大鼠随机分为正常对照组(NC组)、利拉鲁肽对照组(LIR组)、糖尿病组(DM组)和糖尿病+利拉鲁肽组(DM+LIR组)。造模成功后检测各组大鼠血糖、血胰岛素、血脂水平,应用稳态模型评估法评价胰岛素抵抗指数,应用高胰岛素正糖钳夹试验评估胰岛素敏感性,并应用Western-blot检测胰岛组织中自噬标志物微管相关轻链蛋白(LC3)及p62蛋白的变化。结果 DM组与NC组及LIR组相比,血清总胆固醇、甘油三酯、低密度脂蛋白-胆固醇、空腹血糖、胰岛素水平、胰岛素抵抗指数均明显升高(P均<0.05),而在DM+LIR组中,这些指标较DM组均有明显下降(P均<0.05)。胰岛素敏感性在DM组中明显降低,DM+LIR组中得到明显改善(P<0.01)。DM组胰岛LC3-Ⅱ/Ⅰ比值较NC组及LIR组升高,p62蛋白则表达下降。而经利拉鲁肽治疗后LC3-Ⅱ/Ⅰ比值进一步升高,p62蛋白表达则进一步下降。结论 利拉鲁肽治疗可增强糖尿病大鼠胰岛自噬功能及胰岛素敏感性。
Abstract:
Objective To explore the mechanism of glucagon-like peptide-1 receptor agonist(liraglutide)underlying improved insulin sensitivity in diabetic rats.Methods The male Wistar rats were divided into normal control group(NC), liraglutide group(LIR), diabetes mellitus group(DM)and diabetes mellitus + liraglutide group(DM+LIR). After successfully modeling, serum glucose, insulin and blood lipid levels were determined. Insulin resistance was indexed using the homeostasis model assessment and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Western-blot was used to detect the expression of autophagy markers in islets including LC3 and p62.Results Serum total cholesterol, triglyceride, low density lipoprotein-cholesterol, fasting blood glucose, insulin levels and insulin resistance index were significantly higher in the DM group than NC group and LIR group(all P<0.05). Compared with DM group, these indexes were all significantly improved in DM+LIR group(all P<0.05). Insulin sensitivity calculated from the glucose fluid infusion rate(GIR)in DM group was significantly decreased but was also improved in the DM+LIR group(P<0.01). Compared with NC group and LIR group, the expression of LC3-Ⅱ/Ⅰ ratio was increased, whereas p62 protein expression level was decreased in DM group. The ratio of LC3-Ⅱ/Ⅰ was further enhanced, and the expression of p62 protein was further decreased by LIR treatment.Conclusion Liraglutide-therapy enhances islet autophagy and insulin sensitivity in diabetic rats.

参考文献/References:

[1] 中华医学会糖尿病分会.基于胰高血糖素样肽-1降糖药物的临床应用共识[J].中华糖尿病杂志,2014,6(1):14-20.DOI:10.3760/cma.j.issn.1674-5809.2014.01.004.
[2] Greig SL,Scott LJ.Insulin degludec/liraglutide:a review in type 2 Diabetes[J].Drugs,2015,75(13):1523-1534.DOI:10.1007/s40265-015-0448-0.
[3] Tamura K,Minami K,Kudo M,et al.Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice[J].PLoS One,2015,10(5):e0126003.DOI:10.1371/journal.pone.0126003.
[4] Kapodistria K,Tsilibary EP,Kotsopoulou E,et al.Liraglutide,a human glucagon-like peptide-1 analogue,stimulates AKT-dependent survival signalling and inhibits pancreatic β-cell apoptosis[J].J Cell Mol Med,2018,22(6):2970-2980.DOI:10.1111/jcmm.13259.
[5] Olefsky JM,Glass CK.Macrophages,inflammation,and insulin resistance[J].Annu Rev Physiol,2010,72:219-246.DOI:10.1146/annurev-physiol-021909-135846.
[6] Zhou JY,Poudel A,Welchko R,et al.Liraglutide improves insulin sensitivity in high fat diet induced diabetic mice through multiple pathways[J].Eur J Pharmacol,2019,861:172594.DOI:10.1016/j.ejphar.2019.172594.
[7] Chai W,Fu Z,Aylor KW,et al.Liraglutide prevents microvascular insulin resistance and preserves muscle capillary density in high-fat diet-fed rats[J].Am J Physiol Endocrinol Metab,2016,311(3):E640-E648.DOI:10.1152/ajpendo.00205.2016.
[8] Klionsky DJ,Abdelmohsen K,Abe A,et al.Guidelines for the use and interpretation of assays for monitoring autophagy(3rd edition)[J].Autophagy,2016,12(1):1-222.DOI:10.1080/15548627.2015.1100356.
[9] Mathew R,Karp CM,Beaudoin B,et al.Autophagy suppresses tumorigenesis through elimination of p62[J].Cell,2009,137(6):1062-1075.DOI:10.1016/j.cell.2009.03.048.
[10] Kim J,Lim YM,Lee MS.The role of autophagy in systemic metabolism and human-type diabetes[J].Mol Cells,2018,41(1):11-17.DOI:10.14348/molcells.2018.2228
[11] Lo MC,Lu CI,Chen MH,et al.Glycoxidative stress-induced mitophagy modulates mitochondrial fates[J].Ann N Y Acad Sci,2010,1201:1-7.DOI:10.1111/j.1749-6632.2010.05630.x.
[12] Cho HM,Sun W.Molecular cross talk among the components of the regulatory machinery of mitochondrial structure and quality control[J].Exp Mol Med,2020,52(5):730-737.DOI:10.1038/s12276-020-0434-9.
[13] Fan M,Jiang H,Zhang Y,et al.Liraglutide enhances autophagy and promotes pancreatic β cell proliferation to ameliorate type 2 diabetes in high-fat-fed and streptozotocin-treated mice[J].Med Sci Monit,2018,24:2310-2316.DOI:10.12659/msm.906286.
[14] Westermark P,Andersson A,Westermark GT.Islet amyloid polypeptide,islet amyloid,and diabetes mellitus[J].Physiol Rev,2011,91(3):795-826.DOI:10.1152/physrev.00042.2009.
[15] Rivera JF,Gurlo T,Daval M,et al.Human-IAPP disrupts the autophagy/lysosomal pathway in pancreatic β-cell:protective role of p62-positive cytoplasmic inclusions[J].Cell Death Differ,2011,18(3):415-426.DOI:10.1038/cdd.2010.111.
[16] Kim KH,Lee MS.Autophagy--a key player in cellular and body metabolism[J].Nat Rev Endocrinol,2014,10(6):322-337.DOI:10.1038/nrendo.2014.35.

相似文献/References:

[1]李春睿,王静,陈峰,等.GLP-1受体激动剂对糖尿病患者肾功能的影响[J].国际内分泌代谢杂志,2014,(06):401.[doi:10.3760/cma.j.issn.1673-4157.2014.06.011]
　Li Chunrui*,Wang Jing,Chen Feng,et al.Effects of GLP-1 receptor agonists on renal function of diabetics[J].International Journal of Endocrinology and Metabolism,2014,(04):401.[doi:10.3760/cma.j.issn.1673-4157.2014.06.011]
[2]黄珊珊,鲁一兵.长链非编码RNA与糖尿病[J].国际内分泌代谢杂志,2015,(04):271.[doi:10.3760/cma.j.issn.1673-4157.2015.04.016]
　Huang Shanshan*,Lu Yibing..Long non-coding RNA and diabetes mellitus[J].International Journal of Endocrinology and Metabolism,2015,(04):271.[doi:10.3760/cma.j.issn.1673-4157.2015.04.016]
[3]高瑞霄,姚朱华,冯凭,等.尿8-羟基脱氧鸟苷在2型糖尿病及糖尿病合并冠心病患者中的临床意义[J].国际内分泌代谢杂志,2014,(05):295.[doi:10.3760/cma.j.issn.1673-4157.2014.05.002]
　Gao Ruixiao*,Yao Zhuhua,Feng Ping,et al.The clinical significance of urinary 8-hydroxy deoxyguanosine in patients with type 2 diabetes mellitus and diabetic patients with coronary heart disease[J].International Journal of Endocrinology and Metabolism,2014,(04):295.[doi:10.3760/cma.j.issn.1673-4157.2014.05.002]
[4]郑佳,肖新华.葡萄糖稳态的中枢调控作用机制 ——2014年美国糖尿病协会“杰出科学成就奖” 演讲报告解读[J].国际内分泌代谢杂志,2014,(05):305.[doi:10.3760/cma.j.issn.1673-4157.2014.05.004]
　Zheng Jia,Xiao Xinhua.The mechanisms of central nervous system in the control of glucose homeostasis--A summary of 2014 ADA "Outstanding Scientific Achievement Award" Lecture[J].International Journal of Endocrinology and Metabolism,2014,(04):305.[doi:10.3760/cma.j.issn.1673-4157.2014.05.004]
[5]唐勤,邵莉.蛋白乙酰化与胰岛素分泌[J].国际内分泌代谢杂志,2014,(05):313.[doi:10.3760/cma.j.issn.1673-4157.2014.05.007]
　Tang Qin,Shao Li..Protein acetylation and insulin secretion[J].International Journal of Endocrinology and Metabolism,2014,(04):313.[doi:10.3760/cma.j.issn.1673-4157.2014.05.007]
[6]卢婷婷,任思佳,沈捷.人群迁徙对糖尿病患病率的影响及其相关因素[J].国际内分泌代谢杂志,2014,(05):327.[doi:10.3760/cma.j.issn.1673-4157.2014.05.011]
　Lu Tingting,Ren Sijia,Shen Jie..Impact of migration on prevalence of diabetes and risk factors[J].International Journal of Endocrinology and Metabolism,2014,(04):327.[doi:10.3760/cma.j.issn.1673-4157.2014.05.011]
[7]包薇萍,陈国芳,刘超.DPP-4抑制剂的肾保护作用[J].国际内分泌代谢杂志,2014,(05):337.[doi:10.3760/cma.j.issn.1673-4157.2014.05.014]
　Bao Weiping,Chen Guofang,Liu Chao..Renal protective effects of dipeptidyl peptidase-4 inhibitors[J].International Journal of Endocrinology and Metabolism,2014,(04):337.[doi:10.3760/cma.j.issn.1673-4157.2014.05.014]
[8]孟庆冬,陶红.巨噬细胞凋亡与糖尿病动脉粥样硬化[J].国际内分泌代谢杂志,2014,(05):340.[doi:10.3760/cma.j.issn.1673-4157.2014.05.015]
　Meng Qingdong,Tao Hong..Macrophage apoptosis and diabetic atherosclerosis[J].International Journal of Endocrinology and Metabolism,2014,(04):340.[doi:10.3760/cma.j.issn.1673-4157.2014.05.015]
[9]赵荷珺 洪天配.胰高血糖素样肽-1类药物与胰腺安全性[J].国际内分泌代谢杂志,2015,(05):319.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.008]
　Zhao Hejun*,Hong Tianpei..Glucagon-like peptide-1-based therapies and pancreatic safety[J].International Journal of Endocrinology and Metabolism,2015,(04):319.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.008]
[10]吕丹 李晓思 陈树春 王泽普.Betatrophin:糖尿病再生治疗的新希望[J].国际内分泌代谢杂志,2015,(05):351.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.016]
　Lyu Dan*,Li Xiaosi,Chen Shuchun,et al.Betatrophin:new hope for regeneration therapy of diabetes[J].International Journal of Endocrinology and Metabolism,2015,(04):351.[doi:DOI:10.3760/cma.j.issn.1673-4157.2015.05.016]

备注/Memo

备注/Memo:
基金项目:兰州市科技发展指导性计划项目(2019-ZD-38); 兰州大学第一医院基金资助项目(ldyyyn2018-59); 甘肃省内分泌疾病临床医学研究中心(20JR10FA667)
通信作者:傅松波,Email:2358852042@qq.com
更新日期/Last Update: 1900-01-01