Abstract
Mechanistic/Mammalian target of rapamycin (mTOR) orchestrates cellular homeostasis by controlling cell growth, proliferation, metabolism, and survival by integrating various growth factors, nutrients and amino acids. Eccentric synchronization of mTOR has been incriminated in various diseases/disorders like cancer, neurodegenerative disorders, and diabetes mellitus and its complications. Recent reports also highlight the role of mTOR in diabetes and its associated complications. This review tries to fathom the role of mTOR signaling in diabetes mellitus and its complications- diabetic cardiomyopathy, diabetic nephropathy, and diabetic retinopathy and highlights mTOR as a putative target for the development of novel anti-diabetic drug candidates.
Keywords: mTOR, Diabetes mellitus, Insulin resistance, Apoptosis, Diabetic cardiomyopathy, Diabetic nephropathy, Diabetic retinopathy
Graphical Abstract
[http://dx.doi.org/10.2337/dc19-S002] [PMID: 30559228]
[http://dx.doi.org/10.1001/jama.2019.16074] [PMID: 31638662]
[http://dx.doi.org/10.1242/jcs.051011] [PMID: 19812304]
[http://dx.doi.org/10.1016/S0092-8674(02)00808-5] [PMID: 12150925]
[http://dx.doi.org/10.1074/jbc.C200665200] [PMID: 12604610]
[http://dx.doi.org/10.1016/j.cell.2009.03.046] [PMID: 19446321]
[http://dx.doi.org/10.1016/j.cub.2004.06.054] [PMID: 15268862]
[http://dx.doi.org/10.1038/ncb839] [PMID: 12172553]
[http://dx.doi.org/10.1016/j.molcel.2007.03.003] [PMID: 17386266]
[http://dx.doi.org/10.1016/j.cub.2005.02.053] [PMID: 15854902]
[http://dx.doi.org/10.1038/nature02866] [PMID: 15306821]
[http://dx.doi.org/10.1074/jbc.M412179200] [PMID: 15537654]
[http://dx.doi.org/10.1073/pnas.0811321106] [PMID: 19497867]
[http://dx.doi.org/10.2337/db09-1061] [PMID: 20332342]
[http://dx.doi.org/10.1016/j.molcel.2012.09.029] [PMID: 23142081]
[http://dx.doi.org/10.1074/jbc.M807458200] [PMID: 19144649]
[http://dx.doi.org/10.2337/db08-0519] [PMID: 19258434]
[http://dx.doi.org/10.1073/pnas.0803047105] [PMID: 18587048]
[http://dx.doi.org/10.1038/ncomms15755] [PMID: 28598424]
[http://dx.doi.org/10.1016/j.cmet.2017.11.004] [PMID: 29275961]
[http://dx.doi.org/10.1128/MCB.00735-09] [PMID: 19720745]
[http://dx.doi.org/10.1038/ncb2860] [PMID: 24161930]
[http://dx.doi.org/10.1128/MCB.00601-09] [PMID: 19995915]
[http://dx.doi.org/10.1007/s00125-016-4188-9] [PMID: 28004151]
[http://dx.doi.org/10.1016/j.mce.2015.07.023] [PMID: 26213322]
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311586] [PMID: 29449364]
[http://dx.doi.org/10.1016/j.jacc.2013.05.019] [PMID: 23747642]
[http://dx.doi.org/10.1016/0002-9149(72)90595-4] [PMID: 4263660]
[http://dx.doi.org/10.1038/nrendo.2015.216] [PMID: 26678809]
[http://dx.doi.org/10.1161/CIRCRESAHA.114.302022] [PMID: 24481845]
[http://dx.doi.org/10.1371/journal.pone.0054221] [PMID: 23342106]
[http://dx.doi.org/10.1042/CS20171167] [PMID: 28842527]
[http://dx.doi.org/10.1016/j.cell.2007.12.018] [PMID: 18191218]
[http://dx.doi.org/10.1038/ncb2152] [PMID: 21258367]
[http://dx.doi.org/10.1091/mbc.e08-12-1248] [PMID: 19211835]
[http://dx.doi.org/10.1016/S0092-8674(03)00929-2] [PMID: 14651849]
[http://dx.doi.org/10.1016/j.molcel.2008.03.003] [PMID: 18439900]
[http://dx.doi.org/10.1016/j.bbadis.2013.03.013] [PMID: 23524376]
[http://dx.doi.org/10.1016/j.mce.2017.03.029] [PMID: 28363742]
[http://dx.doi.org/10.1016/j.yjmcc.2018.10.004] [PMID: 30292723]
[http://dx.doi.org/10.1002/emmm.201303183] [PMID: 24408966]
[http://dx.doi.org/10.2337/diacare.28.1.164] [PMID: 15616252]
[http://dx.doi.org/10.2147/IJNRD.S40172] [PMID: 25342915]
[http://dx.doi.org/10.1681/ASN.2008111186] [PMID: 19875810]
[http://dx.doi.org/10.1016/j.tem.2016.07.002] [PMID: 27470431]
[http://dx.doi.org/10.2337/diacare.27.2007.S79] [PMID: 14693934]
[http://dx.doi.org/10.1016/j.bbrc.2009.04.136] [PMID: 19422788]
[http://dx.doi.org/10.1016/j.semnephrol.2013.11.003]
[http://dx.doi.org/10.1172/JCI44771] [PMID: 21606597]
[http://dx.doi.org/10.1681/ASN.2012111080] [PMID: 24092929]
[http://dx.doi.org/10.1007/s11892-017-0879-y] [PMID: 28593583]
[http://dx.doi.org/10.3389/fphar.2018.00443] [PMID: 29881349]
[http://dx.doi.org/10.1038/sj.eye.6700133] [PMID: 12032713]
[http://dx.doi.org/10.1016/S0161-6420(03)00475-5] [PMID: 13129861]
[http://dx.doi.org/10.1038/414813a] [PMID: 11742414]
[http://dx.doi.org/10.1016/j.tem.2013.09.005] [PMID: 24183659]
[http://dx.doi.org/10.1016/j.preteyeres.2011.05.002] [PMID: 21635964]
[http://dx.doi.org/10.1016/j.peptides.2012.04.008] [PMID: 22537944]
[http://dx.doi.org/10.1096/fj.01-0658com] [PMID: 12039858]
[http://dx.doi.org/10.1038/cddis.2013.506] [PMID: 24336084]
[http://dx.doi.org/10.1172/JCI0213776] [PMID: 11901189]
[http://dx.doi.org/10.1159/000453207] [PMID: 27997905]
[PMID: 31114980]
[http://dx.doi.org/10.1016/j.biopha.2018.09.140] [PMID: 30372821]
[PMID: 30569107]