World J Diabetes. 2015 Mar 15;6(2):217-24. doi: 10.4239/wjd.v6.i2.217.
mTOR: Driving apoptosis and autophagy for neurocardiac complications of diabetes mellitus.
World journal of diabetes
Kenneth Maiese
Affiliations
Affiliations
- Kenneth Maiese, Cellular and Molecular Signaling, Newark, NJ 07101, United States.
PMID: 25789103
PMCID: PMC4360415 DOI: 10.4239/wjd.v6.i2.217
Abstract
The World Health Organization estimates that diabetes mellitus (DM) will become the seventh leading cause of death during the next two decades. DM affects approximately 350 million individuals worldwide and additional millions that remain undiagnosed are estimated to suffer from the complications of DM. Although the complications of DM can be seen throughout the body, the nervous, cardiac, and vascular systems can be significantly affected and lead to disorders that include cognitive loss, stroke, atherosclerosis, cardiac failure, and endothelial stem cell impairment. At the cellular level, oxidative stress is a significant determinant of cell fate during DM and leads to endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis, and autophagy. Multiple strategies are being developed to combat the complications of DM, but it is the mechanistic target of rapamycin (mTOR) that is gaining interest in drug development circles especially for protective therapies that involve cytokines and growth factors such as erythropoietin. The pathways of mTOR linked to mTOR complex 1, mTOR complex 2, AMP activated protein kinase, and the hamartin (tuberous sclerosis 1)/tuberin (tuberous sclerosis 2) complex can ultimately influence neuronal, cardiac, and vascular cell survival during oxidant stress in DM through a fine interplay between apoptosis and autophagy. Further understanding of these mTOR regulated pathways should foster novel strategies for the complications of DM that impact millions of individuals with death and disability.
Keywords: Apoptosis; Autophagy; Cardiac disease; Diabetes mellitus; Erythropoietin; Mechanistic target of rapamycin; Metformin; Neurodegeneration; Oxidative stress; Vascular disease
References
- Diabetes. 2011 Jun;60(6):1770-8 - PubMed
- Diabetes. 2012 Feb;61(2):272-80 - PubMed
- Endocr Res. 2011;36(3):116-23 - PubMed
- J Diabetes Res. 2013;2013:585897 - PubMed
- Histol Histopathol. 2005 Jan;20(1):299-315 - PubMed
- Vascul Pharmacol. 2012 Nov-Dec;57(5-6):139-49 - PubMed
- Cardiovasc Diabetol. 2012 Oct 15;11:129 - PubMed
- Cardiovasc Res. 2013 Mar 1;97(3):393-403 - PubMed
- Diabetes. 2015 Jan;64(1):36-48 - PubMed
- J Diabetes Res. 2013;2013:473575 - PubMed
- Aging (Albany NY). 2012 Jun;4(6):436-47 - PubMed
- Exp Gerontol. 2010 Mar;45(3):217-34 - PubMed
- Exp Diabetes Res. 2012;2012:836759 - PubMed
- Ageing Res Rev. 2013 Jan;12(1):103-15 - PubMed
- Curr Neurovasc Res. 2010 May;7(2):95-112 - PubMed
- Curr Neurovasc Res. 2007 Feb;4(1):63-71 - PubMed
- Ann Med. 2014 Dec;46(8):587-96 - PubMed
- Int J Mol Sci. 2012 Oct 26;13(11):13830-66 - PubMed
- Biochim Biophys Acta. 2010 Jul-Aug;1802(7-8):593-600 - PubMed
- J Neurochem. 2014 Jul;130(2):172-84 - PubMed
- Trends Mol Med. 2013 Jan;19(1):51-60 - PubMed
- Exp Cell Res. 2013 Aug 15;319(14 ):2296-306 - PubMed
- Diabetes Obes Metab. 2014 Sep;16 Suppl 1:4-15 - PubMed
- Curr Neurovasc Res. 2008 Aug;5(3):159-70 - PubMed
- Curr Neurovasc Res. 2012 May;9(2):91-101 - PubMed
- J Proteome Res. 2014 May 2;13(5):2433-44 - PubMed
- Mol Cell Endocrinol. 2010 Jun 10;321(2):194-206 - PubMed
- Aging Cell. 2014 Dec;13(6):1075-85 - PubMed
- Br J Pharmacol. 2014 Jun;171(11):2739-50 - PubMed
- PLoS One. 2013 Dec 09;8(12):e82287 - PubMed
- Curr Pharm Des. 2013;19(32):5663-77 - PubMed
- Diabetes. 2006 Apr;55(4):1022-8 - PubMed
- Nat Commun. 2014 Sep 26;5:4934 - PubMed
- Prog Neurobiol. 2008 Jun;85(2):194-213 - PubMed
- Diabetol Metab Syndr. 2014 Jul 28;6(1):80 - PubMed
- Am J Physiol Regul Integr Comp Physiol. 2014 Nov 15;307(10):R1198-206 - PubMed
- Curr Neurovasc Res. 2011 May;8(2):103-20 - PubMed
- Mol Cell. 2008 Apr 25;30(2):214-26 - PubMed
- Cell Signal. 2011 Aug;23 (8):1311-9 - PubMed
- Histol Histopathol. 2007 Nov;22(11):1251-67 - PubMed
- Curr Neurovasc Res. 2010 Feb;7(1):59-64 - PubMed
- DNA Cell Biol. 2013 Feb;32(2):41-9 - PubMed
- Exp Neurol. 2012 Jan;233(1):68-78 - PubMed
- Int J Mol Sci. 2012;13(9):11102-29 - PubMed
- Prog Neurobiol. 2012 Nov;99(2):128-48 - PubMed
- Wound Repair Regen. 2014 Jan-Feb;22(1):23-33 - PubMed
- Nature. 2012 Jan 18;481(7382):511-5 - PubMed
- Clin Chem Lab Med. 2011 Nov;49(11):1773-82 - PubMed
- Br J Pharmacol. 2014 Jan;171(2):523-35 - PubMed
- Acta Neuropathol Commun. 2014 Jul 08;2:71 - PubMed
- Mol Cell Biochem. 2014 Jan;385(1-2):125-32 - PubMed
- Behav Brain Res. 2013 Feb 1;238:44-7 - PubMed
- Biol Pharm Bull. 2014;37(7):1248-52 - PubMed
- Int J Mol Sci. 2014 Sep 22;15(9):16848-84 - PubMed
- Lab Anim Res. 2012 Jun;28(2):99-107 - PubMed
- Diabetologia. 2012 Nov;55(11):3128-40 - PubMed
- Clin Sci (Lond). 2009 Feb;116(3):191-203 - PubMed
- Genes Dev. 2008 Jan 15;22(2):239-51 - PubMed
- Curr Mol Med. 2014 Jan;14(1):3-21 - PubMed
- J Diabetes. 2015 Mar;7(2):231-9 - PubMed
- Curr Neurovasc Res. 2013 Feb;10(1):29-38 - PubMed
- J Agric Food Chem. 2012 Feb 1;60(4):1094-101 - PubMed
- Int J Biol Sci. 2014 Aug 23;10(8):921-39 - PubMed
- J Endocrinol. 2012 May;213(2):143-54 - PubMed
- Curr Med Chem. 2007;14(16):1729-38 - PubMed
- Diabetes. 2013 Apr;62(4):1270-81 - PubMed
- ScientificWorldJournal. 2009 Oct 02;9:1072-104 - PubMed
- J Clin Pharmacol. 2011 Feb;51(2):128-52 - PubMed
- Rev Endocr Metab Disord. 2014 Mar;15(1):79-97 - PubMed
- Cardiovasc Diabetol. 2011 Aug 10;10 :75 - PubMed
- Basic Res Cardiol. 2013 May;108(3):352 - PubMed
- Brain Behav Immun. 2014 Nov;42:157-68 - PubMed
- J Neurochem. 2011 Aug;118(4):460-74 - PubMed
- Redox Rep. 2004;9(2):111-6 - PubMed
- J Biol Chem. 2014 Feb 14;289(7):4145-60 - PubMed
- Neurobiol Dis. 2011 Jul;43(1):86-98 - PubMed
- J Neurosci. 2013 Aug 7;33(32):13138-49 - PubMed
- Br J Pharmacol. 2014 Jul;171(13):3146-57 - PubMed
- J Diabetes Res. 2014;2014:628591 - PubMed
- Int J Mol Sci. 2014 May 05;15(5):7667-83 - PubMed
- Diabetes. 2010 Oct;59(10):2426-34 - PubMed
- Sci Rep. 2014 Jul 01;4:5519 - PubMed
- Cardiovasc Diabetol. 2010 Sep 01;9:46 - PubMed
- Molecules. 2009 Sep 09;14(9):3446-85 - PubMed
- Neural Regen Res. 2014 Aug 1;9(15):1413-7 - PubMed
- Int J Mol Sci. 2014 Jun 10;15(6):10296-333 - PubMed
- PLoS One. 2014 Jul 11;9(7):e102013 - PubMed
- JAMA. 2005 Jan 5;293(1):90-5 - PubMed
- Cardiovasc Diabetol. 2014 Feb 12;13:42 - PubMed
- Antioxid Redox Signal. 2013 Apr 1;18(10 ):1141-53 - PubMed
- Neuroendocrinology. 2013;97(4):300-8 - PubMed
- Mol Cell Neurosci. 2011 Jun;47(2):145-53 - PubMed
- PLoS One. 2014 Jan 28;9(1):e86252 - PubMed
- FASEB J. 2015 Feb;29(2):589-96 - PubMed
- Cell Signal. 2012 Jan;24(1):17-24 - PubMed
- Am J Epidemiol. 2012 Jul 15;176(2):99-107 - PubMed
- Aging (Albany NY). 2012 Mar;4(3):187-201 - PubMed
- Am J Physiol Heart Circ Physiol. 2011 Jun;300(6):H2123-34 - PubMed
- J Biol Chem. 2013 Aug 9;288(32):23194-202 - PubMed
- Expert Opin Drug Discov. 2013 Jan;8(1):35-48 - PubMed
- J Biol Chem. 2011 May 27;286(21):18465-73 - PubMed
- Age (Dordr). 2013 Oct;35(5):1531-44 - PubMed
- Exp Biol Med (Maywood). 2011 Sep;236(9):1051-63 - PubMed
- Peptides. 2013 Jan;39:71-9 - PubMed
- JAMA. 2006 Apr 12;295(14):1681-7 - PubMed
- Neurosci Lett. 2012 Dec 7;531(2):176-81 - PubMed
- Endocrinology. 2014 Apr;155(4):1207-21 - PubMed
- J Alzheimers Dis. 2012;29(1):89-98 - PubMed
- BMC Neurosci. 2012 Jan 19;13:11 - PubMed
- Bone. 2012 Feb;50(2):437-43 - PubMed
- Curr Neurovasc Res. 2011 Nov;8(4):270-85 - PubMed
- Arch Neurol. 2009 Mar;66(3):315-22 - PubMed
- Comp Biochem Physiol B Biochem Mol Biol. 2012 Sep;163(1):51-8 - PubMed
- Cardiovasc Diabetol. 2012 Jul 16;11:45 - PubMed
- Heart Fail Rev. 2014 Jan;19(1):113-21 - PubMed
- Expert Opin Ther Targets. 2012 Dec;16(12):1203-14 - PubMed
- Curr Neurovasc Res. 2007 Aug;4(3):194-204 - PubMed
- J Mol Endocrinol. 2014 Jan 09;52(1):67-76 - PubMed
- J Cell Biochem. 2012 Jan;113(1):220-8 - PubMed
- Int J Mol Med. 2012 Apr;29(4):613-8 - PubMed
- Rom J Morphol Embryol. 2011;52(4):1173-85 - PubMed
- Biomed Pharmacother. 2010 Dec;64(10):681-5 - PubMed
- PLoS One. 2012;7(9):e45456 - PubMed
- Curr Neurovasc Res. 2014 May;11(2):177-86 - PubMed
- Cell Biochem Funct. 2009 Oct;27(7):473-8 - PubMed
- Exp Mol Med. 2014 Aug 29;46:e111 - PubMed
- Diabetes. 1996 Apr;45(4):471-7 - PubMed
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