mTOR调控自噬参与糖尿病并发症的研究进展

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1200-1204.

mTOR调控自噬参与糖尿病并发症的研究进展

钱子冰^1,2, 刘静², 曾佩芸¹, 张琦^2*

1.甘肃中医药大学,甘肃兰州 730000;
2.甘肃省人民医院内分泌科,甘肃兰州 730000

收稿日期:2020-06-27 修回日期:2020-10-13 出版日期:2021-08-05 发布日期:2021-07-21
通讯作者: *lzzq78@126.com
基金资助:
国家自然科学基金 (81760151)

Research progress of autophagy regulated by mTOR in diabetic complications

QIAN Zi-bing^1,2, LIU Jing², ZENG Pei-yun¹, ZHANG Qi^2*

1. Gansu University of Traditional Chinese Medicine, Lanzhou 730000;
2. Department of Endocrinology, Gansu Provincial People's Hospital,Lanzhou 730000,China

Received:2020-06-27 Revised:2020-10-13 Online:2021-08-05 Published:2021-07-21
Contact: *lzzq78@126.com

摘要/Abstract

摘要： 在糖尿病状态下,失调的自噬可能导致多个脏器的病变。mTOR介导的自噬参与糖尿病并发症及合并疾病的调控机制,如糖尿病肾病、非酒精性脂肪肝、糖尿病心脏病、糖尿病性视网膜病变、糖尿病周围神经病变等。对糖尿病自噬机制的研究将有助于发现新的治疗靶点,更好的预防和治疗糖尿病并发症。

关键词: mTOR, 自噬, 新型降糖药物, 糖尿病并发症

Abstract: In the state of diabetes, dysfunctional autophagy may lead to pathological changes of multiple organs. The mTOR-mediated autophagy is involved in the regulation of diabetic complications and concomitant diseases, such as diabetic nephropathy, non-alcoholic fatty liver, diabetic heart disease, diabetic retinopathy, diabetic peripheral neuropathy and so on. The study on the mechanism of diabetic autophagy will help to find new therapeutic targets and better methods to prevent and treat diabetic complications.

Key words: mTOR, autophagy, new hypoglycemic drugs, diabetic complications

中图分类号:

R589.9

钱子冰, 刘静, 曾佩芸, 张琦. mTOR调控自噬参与糖尿病并发症的研究进展[J]. 基础医学与临床, 2021, 41(8): 1200-1204.

QIAN Zi-bing, LIU Jing, ZENG Pei-yun, ZHANG Qi. Research progress of autophagy regulated by mTOR in diabetic complications[J]. Basic & Clinical Medicine, 2021, 41(8): 1200-1204.

参考文献

[1]Cao Y, Luo Y, Zou J, et al. Autophagy and its role in gastric cancer[J]. Clin Chim Acta, 2019,489:10-20.
[2]Menzies FM, Fleming A, Caricasole A, et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities[J]. Neuron, 2017, 93: 1015-1034.
[3]Maiese K. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR[J]. Neural Regen Res, 2016, 11: 372-385.
[4]Miao XY, Gu ZY, Liu P, et al. The human glucagon-like peptide-1 analogue liraglutide regulates pancreatic beta-cell proliferation and apoptosis via an AMPK/mTOR/P70S6K signaling pathway[J]. Peptides, 2013, 39:71-79.
[5]Peng N, Meng N, Wang S, et al. An activator of mTOR inhibits oxLDL-induced autophagy and apoptosis in vascular endothelial cells and restricts atherosclerosis in apolipoprotein E^-/- mice[J]. Sci Rep, 2014, 4:1-9.
[6]Gu Y, Ma CT, Gu HL, et al. Sitagliptin improves cardiac function after myocardial infarction through activation of autophagy in streptozotocin-induced diabetic mice[J]. Eur Rev Med Pharmacol Sci,2018,22:8973-8983.
[7]Mizuno M, Kuno A, Yano T, et al. Empagliflozin normalizes the size and number of mitochondria and prevents reduction in mitochondrial size after myocardial infarction in diabetic hearts[J]. Physiol Rep, 2018, 6: e13741.doi:10.14814/phy2.13741.
[8]Shao N, Yu XY, Ma XF, et al. Exenatide delays the progression of nonalcoholic fatty liver disease in C57BL/6 mice, which may involve inhibition of the NLRP3 inflammasome through the mitophagy pathway[J]. Gastroenterol Res Pract, 2018,15:1864307.doi:10.1155/2018/1864307.
[9]Furuichi K, Shimizu M, Hara A, et al. Diabetic nephropathy: A comparison of the clinical and pathological features between the CKD risk classification and the classification of diabetic nephropathy 2014 in Japan[J].Intern Med, 2018,57:3345-3350.
[10]Puelles VG, Van Der Wolde JW, Wanner N, et al. mTOR-mediated podocyte hypertrophy regulates glomerular integrity in mice and humans[J]. JCI Insight, 2019,19:e99271.doi:10.1172/jci.insight.99271.
[11]Inoki K, Mori H, Wang J, et al. mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice[J]. J Clin Invest, 2011, 121: 2181-2196.
[12]Horas HNS, Nishiumi S, Kawano Y, et al. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease[J]. Arch Biochem Biophys, 2017, 623-624:64-75.
[13]Smith BK, Marcinko K, Desjardins EM, et al. Treatment of nonalcoholic fatty liver disease: role of AMPK[J]. Am J Physiol Endocrinol Metab, 2016, 311: 730-740.
[14]Guha P, Tyagi R, Chowdhury S, et al. IPMK mediates activation of ULK signaling and transcriptional regulation of autophagy linked to liver inflammation and regeneration[J]. Cell Rep, 2019, 26: 2692-2703.
[15]Shi C, Xue W, Han B, et al. Acetaminophen aggravates fat accumulation in NAFLD by inhibiting autophagy via the AMPK/mTOR pathway[J]. Eur J Pharmacol, 2019, 850:15-22.
[16]Dunlay SM, Givertz MM, Aguilar D, et al. Type 2 diabetes mellitus and heart failure: A scientific statement from the american heart association and the heart failure society of america: This statement does not represent an update of the 2017 ACC/AHA/HFSA heart failure guide-line update[J]. Circulation, 2019, 140:294-324.
[17]Kandemir YB, Tosun V, Güntekin Ü. Melatonin protects against streptozotocin-induced diabetic cardiomyopathy through the mammalian target of rapamycin (mTOR) signaling pathway[J]. Adv Clin Exp Med, 2019, 28: 1171-1177.
[18]Yang F, Qin Y, Wang Y, et al. Metformin inhibits the NLRP3 inflammasome via AMPK/mTOR-dependent effects in diabetic cardiomyopathy[J]. Int J Biol Sci, 2019, 15: 1010-1019.
[19]Zeng J, Zhao H, Chen B. DJ-1/PARK7 inhibits high glucose-induced oxidative stress to prevent retinal pericyte apoptosis via the PI3K/AKT/mTOR signaling pathway[J]. Exp Eye Res, 2019,189:107830.doi:10.1016/j.exer.2019d07830.
[20]Chen H, Ji Y, Yan X, et al. Berberine attenuates apoptosis in rat retinal Müller cells stimulated with high glucose via enhancing autophagy and the AMPK/mTOR signaling[J]. Biomed Pharmacother, 2018, 108:1201-1207.
[21]Liu X, Zhao X, Cheng R, et al. Autophagy attenuates high glucose-induced oxidative injury to lens epithelial cells[J]. Bioence Rep, 2020, 40:1-31
[22]Wu LY, Li M, Qu ML, et al. High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway in keratinocytes: A potential mechanism and therapeutic target for diabetic small fiber neuropathy[J]. Mol Cell Endocrinol, 2018, 472:107-116.
[23]Liu SY, Chen L, Li XC, et al. Lycium barbarum polysaccharide protects diabetic peripheral neuropathy by enhancing autophagy via mTOR/p70S6K inhibition in Streptozotocin-induced diabetic rats[J]. J Chem Neuroanat, 2018, 89:37-42.
[24]El Hiani Y, Egom EE, Dong XP. mTOR signalling: jack-of-all-trades[J]. Biochem Cell Biol, 2019, 97: 58-67.
[25]Su Y, Wu J, He J, et al. High insulin impaired ovarian function in early pregnant mice and the role of autophagy in this process[J]. Endocr J, 2017, 64: 613-621.