Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2022, Vol. 36 ›› Issue (5): 30-34.doi: 10.6040/j.issn.1673-3770.0.2021.125

Previous Articles    

GLP-1 protected the diabetic retinopathy through induction of autophagy in rats

SU Jie1, YANG Fuyu1, LI Meng1, CHEN Huiru2, JIANG Lisheng3, WANG Lixiang4   

  1. 1. Department of Ophthalmology, Affiliated hospital of North China University of Science and Technology, Tangshan 063000, He bei, China;
    2. Department of Ophthalmology, Tangshan Nanhu Hospital, Tangshan 063000, Hebei, China;
    3. Department of Ophthalmology, Luanzhou Peoples Hospital, Luanzhou 063700, Hebei, China;
    4. Department of Ophthalmology, Luannan County Hospital, Luannan 063500, Hebei, China
  • Published:2022-09-20

PDF (PC)

108

Abstract: Objective Research the GLP-1 induced autophagy through regulation of mTOR signaling pathways, whether there is a protective role in diabetic retinopathy rats. Methods Conform to the requirements of the diabetic retinopathy rats model, divided into model group, insulin group and GLP-1 group, each group of 6, ALL the groups were measured to realise the fasting blood glucose level in rats after 0 d,4 w, 8 w and 12 w, after 12 w killing the rats, we removed the retinal tissue for HE staining and test the expression of P53, LC3 by immunohistochemical method. Collected blood serum to detect oxidative stress product ROS and MDA content with serum superoxide dismutase(SOD)method. Detected mTOR protein expression with Western blotting method. Results Compared with model group, insulin group and GLP-1 group can obviously reduce fasting blood glucose, the difference was statistically significant, and is no statistically significant difference in the two groups. HE staining showed the retinal ganglion cells of model group disordered arrangement and the cells reduced or missed, but in insulin group and GLP-1 group, retinal ganglion cells arrangement was neat, no significant decline, close to normal. Immunohistochemical display, The LC3 and P53 protein expression respectively(2.34±0.13,0.46±0.03)in GLP-1 group increased significantly compared with other groups, and the differences were statistically significance(P<0.05). Oxidative stress product ROS and MDA content respectively(74.68±4.08,55.60±1.50)in GLP-1 group reduced, compared with other groups, the differences between groups were statistically significant(P<0.05). Compared with other groups, mTOR protein content(0.43±0.04)in GLP-1 group decreased, and the differences between groups were statistically significant(F=105.447, P<0.05). Conclusion Glp-1 may through activation of autophagy by regulating mTOR signaling pathways, then reducing oxidative stress injury of retina, as to protect the retina.

Key words: GLP-1, Autophagy, Oxidative stress reaction, mTOR

CLC Number: 

  • R774
[1] Gudla S, Tenneti D, Pande M, et al. Diabetic retinopathy: pathogenesis, treatment, and complications[M] //Drug Delivery for the Retina and Posterior Segment Disease. Cham: Springer International Publishing, 2018: 83-94. doi:10.1007/978-3-319-95807-1_5.
[2] 雷雨, 郑宏华, 陈小红, 等. GLP-1防治糖尿病视网膜病变的研究进展[J]. 眼科新进展, 2017, 37(12): 1193-1196. doi:10.13389/j.cnki.rao.2017.0301. LEI Yu, ZHENG Honghua, CHEN Xiaohong, et al. Research advance in GLP-1 for the treatment of diabetic retinopathy[J]. Recent Advances in Ophthalmology, 2017, 37(12): 1193-1196. doi:10.13389/j.cnki.rao.2017.0301.
[3] He Q, Sha S, Sun L, et al. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway[J]. Biochem Biophys Res Commun, 2016, 476(4): 196-203. doi:10.1016/j.bbrc.2016.05.086.
[4] 杨双莉. GLP-1抑制mTOR通路激活自噬改善糖尿病肾脏病作用机制的研究[D]. 广州: 南方医科大学, 2017: 1-71.
[5] Noyan-Ashraf MH, Shikatani EA, Schuiki I, et al. A glucagon-like peptide-1 analog reverses the molecular pathology and cardiac dysfunction of a mouse model of obesity[J]. Circulation, 2013, 127(1): 74-85. doi:10.1161/circulationaha.112.091215.
[6] 刘青, 艾明. 雷珠单抗联合全视网膜光凝辅助玻璃体切割手术治疗糖尿病视网膜病变[J]. 国际眼科杂志, 2016, 16(9): 1637-1640. doi:10.3980/j.issn.1672-5123.2016.9.09. LIU Qing, AI Ming. Effect of Ranibizumab and panretinal photocoagulation in the treatment of proliferative diabetic retinopathy with vitreoretinal surgery[J]. International Eye Science, 2016, 16(9): 1637-1640. doi:10.3980/j.issn.1672-5123.2016.9.09.
[7] 帅天姣, 代海燕, 张召弟, 等. β-榄香烯对糖尿病性视网膜病变增殖期大鼠视网膜中VEGF表达的干预作用[J]. 中国当代医药, 2018, 25(18): 7-9, 16. doi:10.3969/j.issn.1674-4721.2018.18.003. SHUAI Tianjiao, DAI Haiyan, ZHANG Zhaodi, et al. Intervention effect of β-elemene on the expression of VEGF in the Retina of rats with diabetic retinopathy during proliferating phase[J]. China Modern Medicine, 2018, 25(18): 7-9, 16. doi:10.3969/j.issn.1674-4721.2018.18.003.
[8] Candeias EM, Sebastião IC, Cardoso SM, et al. Gut-brain connection: the neuroprotective effects of the anti-diabetic drug liraglutide[J]. World J Diabetes, 2015, 6(6): 807-827. doi:10.4239/wjd.v6.i6.807.
[9] Hernández C, Bogdanov P, Corraliza L, et al. Topical administration of GLP-1 receptor agonists prevents retinal neurodegeneration in experimental diabetes[J]. Diabetes, 2016, 65(1): 172-187. doi:10.2337/db15-0443.
[10] Fan Y, Liu K, Wang Q, et al. Exendin-4 alleviates retinal vascular leakage by protecting the blood-retinal barrier and reducing retinal vascular permeability in diabetic Goto-Kakizaki rats[J]. Exp Eye Res, 2014, 127: 104-116. doi:10.1016/j.exer.2014.05.004.
[11] 苏杰, 艾昕, 马春梅, 等. 急性高眼压大鼠外侧膝状体神经元细胞自噬与凋亡的关系[J]. 山东大学耳鼻喉眼学报, 2018, 32(4): 68-71. doi:10.6040/j.issn.1673-3770.0.2017.550. Su Jie, Ai Xin, Ma Chunmei, et al. Relationship between acute intraocular hypertension and lateral geniculate neuron autophagy and apoptosis in rats[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(4): 68-71. doi:10.6040/j.issn.1673-3770.0.2017.550.
[12] 杨丽, 胡淑芳, 曾天舒. 利拉鲁肽对胰岛素抵抗小鼠肝脏组织自噬影响的研究[J]. 中国糖尿病杂志, 2019, 27(4): 287-293. doi:10.3969/j.issn.1006-6187.2019.04.011. YANG Li, HU Shufang, ZENG Tianshu. The role of Liraglutide on hepatic autophagy in mice models of insulin resistance[J]. Chinese Journal of Diabetes, 2019, 27(4): 287-293. doi:10.3969/j.issn.1006-6187.2019.04.011.
[13] Zhou J, Wu J, Zheng F, et al. Glucagon-like peptide-1 analog-mediated protection against cholesterol-induced apoptosis via mammalian target of rapamycin activation in pancreatic βTC-6 cells-1mTORβTC-6[J]. J Diabetes, 2015, 7(2): 231-239. doi:10.1111/1753-0407.12177.
[14] He Q, Sha S, Sun L, et al. GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway[J]. Biochem Biophys Res Commun, 2016, 476(4): 196-203. doi:10.1016/j.bbrc.2016.05.086.
[15] Jalewa J, Sharma MK, Gengler S, et al. A novel GLP-1/GIP dual receptor agonist protects from 6-OHDA lesion in a rat model of Parkinson's disease[J]. Neuropharmacology, 2017, 117: 238-248. doi:10.1016/j.neuropharm.2017.02.013.
[16] Zhao X, Liu G, Shen H, et al. Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells[J]. Int J Mol Med, 2015, 35(3): 684-692. doi:10.3892/ijmm.2014.2052.
[17] 许红玲, 张萍. 自噬与肿瘤耐药关系的研究进展[J]. 上海交通大学学报(医学版), 2016, 36(6): 934-938. doi:10.3969/j.issn.1674-8115.2016.06.030. XU Hongling, ZHANG Ping. Research progresses of relationship between autophagy and drug resistance of tumor[J]. Journal of Shanghai Jiao Tong University(Medical Science), 2016, 36(6): 934-938. doi:10.3969/j.issn.1674-8115.2016.06.030.
[18] Lenoir O, Jasiek M, Hénique C, et al. Endothelial cell and podocyte autophagy synergistically protect from diabetes-induced glomerulosclerosis[J]. Autophagy, 2015, 11(7): 1130-1145. doi:10.1080/15548627.2015.1049799.
[19] Ezaki J, Matsumoto N, Takeda-Ezaki M, et al. Liver autophagy contributes to the maintenance of blood glucose and amino acid levels[J]. Autophagy, 2011, 7(7): 727-736. doi:10.4161/auto.7.7.15371.
[20] Zhang ZJ, Wang X, Ma CZ, et al. Genipin protects rats against lipopolysaccharide-induced acute lung injury by reinforcing autophagy[J]. Int Immunopharmacol, 2019, 72: 21-30. doi:10.1016/j.intimp.2019.03.052.
[21] Liang J, Shao SH, Xu ZX, et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1)phosphorylation mediating the decision to enter autophagy or apoptosis[J]. Nat Cell Biol, 2007, 9(2): 218-224. doi:10.1038/ncb1537.
[22] Mao K, Shu W, Qiu Q, et al. Salvianolic acid A protects retinal pigment epithelium from OX-LDL-induced inflammation in an age-related macular degeneration model[J]. Discov Med, 2017, 23(125): 129-147.
[23] 史亦男, 张楠, 崔圆, 等. 氧化应激与糖尿病及其血管并发症研究进展[J]. 中国老年学杂志, 2016, 36(18): 4664-4666. doi:10.3969/j.issn.1005-9202.2016.18.128.
[24] 董一, 万光明, 闫磐石, 等. 醛糖还原酶和晚期糖基化终末产物受体对糖尿病视网膜病变神经元凋亡的影响[J]. 眼科新进展, 2019, 39(8): 741-745. doi:10.13389/j.cnki.rao.2019.0169. DONG Yi, WAN Guangming, YAN Panshi, et al. Effects of aldose reductase and advanced glycation end products receptor on neuronal apoptosis in diabetic retinopathy[J]. Recent Advances in Ophthalmology, 2019, 39(8): 741-745. doi:10.13389/j.cnki.rao.2019.0169.
[25] 王晓民, 职康康, 邹思力, 等. GLP-1对高糖诱导内皮细胞损伤的保护作用及分子机制研究[J]. 海南医学院学报, 2017, 23(21): 2899-2902. doi:10.13210/j.cnki.jhmu.20171025.003. WANG Xiaomin, ZHI Kangkang, ZOU Sili, et al. The protective effect and molecular mechanism of GLP-1 on the high glucose-induced endothelial cell injury[J]. Journal of Hainan Medical University, 2017, 23(21): 2899-2902. doi:10.13210/j.cnki.jhmu.20171025.003.
[26] 刘珺玲, 魏蕊, 洪天配. 我国GLP-1受体激动剂治疗糖尿病的临床与基础研究[J]. 中国科学(生命科学), 2018, 48(8): 917-925. doi:10.1360/N052018-00030. LIU Junling, WEI Rui, HONG Tianpei. Clinical and basic studies of GLP-1 receptor agonists for the treatment of diabetes in China[J]. Science in China(Series C), 2018, 48(8): 917-925. doi:10.1360/N052018-00030.
[27] Hong TP, Liu JL, Wei R. Clinical and basic studies of GLP-1 receptor agonists for the treatment of diabetes in China[J]. Sci Sin-Vitae, 2018, 48(8): 917-925. doi:10.1360/n052018-00030.
[1] YAO ZhouzhouOverview. Tetrandrine regulates autophagy in tumor cells [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(2): 139-143.
[2] Ruibao LIU,Ying ZHAO,Minglu GUO,Yu DUAN,Yanxia WU,Xuejing LU. Autophagy and its research progress in glaucoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(5): 158-161.
[3] SU Jie, AI Xin, MA Chunmei, YANG Fuyu, HUANG Shuai. Relationship between acute intraocular hypertension and lateral geniculate neuron autophagy and apoptosis in rats [J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(4): 68-71.
[4] ZHANG Jinling, CAI Xiaolan, LI Xuezhong, FENG Xin, QI Junjun, LIU Dayu. Study of autophagy-related genes atg3, ambra1 expressions in chronic rhinosinusitis without or with nasal polyps accompanied with asthma. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(2): 50-55.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Website Copyright: Editorial Office of Journal of Otolaryngology and Ophthalmology of Shandong University
Address: No.27 Shanda South Road, Jinan, Shandong, China. Post code: 250100 Tel: +86-0531-88366912 Email: ebhxb@sdu.edu.cn Supported by Beijing Magtech Co.Ltd