Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?
CV risk
diabetes
endothelial dysfunction
metformin
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
22 Dec 2020
22 Dec 2020
Historique:
received:
30
11
2020
revised:
18
12
2020
accepted:
21
12
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
31
12
2020
Statut:
epublish
Résumé
Cardiovascular mortality is a major cause of death among in type 2 diabetes (T2DM). Endothelial dysfunction (ED) is a well-known important risk factor for the development of diabetes cardiovascular complications. Therefore, the prevention of diabetic macroangiopathies by preserving endothelial function represents a major therapeutic concern for all National Health Systems. Several complex mechanisms support ED in diabetic patients, frequently cross-talking each other: uncoupling of eNOS with impaired endothelium-dependent vascular response, increased ROS production, mitochondrial dysfunction, activation of polyol pathway, generation of advanced glycation end-products (AGEs), activation of protein kinase C (PKC), endothelial inflammation, endothelial apoptosis and senescence, and dysregulation of microRNAs (miRNAs). Metformin is a milestone in T2DM treatment. To date, according to most recent EASD/ADA guidelines, it still represents the first-choice drug in these patients. Intriguingly, several extraglycemic effects of metformin have been recently observed, among which large preclinical and clinical evidence support metformin's efficacy against ED in T2DM. Metformin seems effective thanks to its favorable action on all the aforementioned pathophysiological ED mechanisms. AMPK pharmacological activation plays a key role, with metformin inhibiting inflammation and improving ED. Therefore, aim of this review is to assess metformin's beneficial effects on endothelial dysfunction in T2DM, which could preempt development of atherosclerosis.
Identifiants
pubmed: 33375185
pii: biomedicines9010003
doi: 10.3390/biomedicines9010003
pmc: PMC7822116
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Références
Exp Mol Med. 2016 Jul 15;48(7):e245
pubmed: 27416781
Cardiovasc Diabetol. 2016 Aug 05;15(1):109
pubmed: 27496150
J Am Heart Assoc. 2014 Mar 26;3(2):e000434
pubmed: 24670789
Acta Physiol (Oxf). 2017 Jan;219(1):22-96
pubmed: 26706498
Circulation. 2004 Jul 13;110(2):186-92
pubmed: 15197144
Diabetes Care. 2019 Jan;42(Suppl 1):S90-S102
pubmed: 30559235
Pharmacol Ther. 2017 Sep;177:44-55
pubmed: 28223234
Biochem Soc Trans. 2003 Feb;31(Pt 1):202-6
pubmed: 12546685
J Am Soc Nephrol. 2003 Aug;14(8 Suppl 3):S227-32
pubmed: 12874436
Diabetes Obes Metab. 2011 Mar;13(3):221-8
pubmed: 21205121
Vascul Pharmacol. 2018 Apr;103-105:29-35
pubmed: 29339138
J Clin Invest. 2010 Jul;120(7):2355-69
pubmed: 20577053
J Clin Invest. 1994 Sep;94(3):1172-9
pubmed: 8083357
Cardiovasc Res. 2008 Jul 15;79(2):341-51
pubmed: 18440987
Pharmacol Ther. 2018 Dec;192:150-162
pubmed: 30056057
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002966
pubmed: 16034881
Diabetes. 2015 Jun;64(6):2028-41
pubmed: 25552600
Diabetes. 1994 Sep;43(9):1122-9
pubmed: 8070612
JAMA. 2019 Oct 1;322(13):1312
pubmed: 31573630
J Clin Invest. 1996 Jun 1;97(11):2601-10
pubmed: 8647954
Redox Biol. 2019 Jan;20:247-260
pubmed: 30384259
J Cell Physiol. 2007 Sep;212(3):682-9
pubmed: 17443690
Rev Endocr Metab Disord. 2013 Mar;14(1):5-12
pubmed: 23306778
J Clin Endocrinol Metab. 2012 Aug;97(8):2862-71
pubmed: 22639289
Toxicol Pathol. 2010 Oct;38(6):856-71
pubmed: 20716788
Diabetes. 2002 Nov;51(11):3274-82
pubmed: 12401719
Can J Physiol Pharmacol. 2020 Jul;98(7):415-430
pubmed: 32150686
Handb Exp Pharmacol. 2020 Nov 03;:
pubmed: 33140223
Circ Res. 2017 May 26;120(11):1825-1841
pubmed: 28546359
J Biol Chem. 2001 May 25;276(21):17625-8
pubmed: 11292821
J Bioenerg Biomembr. 2006 Feb;38(1):33-42
pubmed: 16732470
J Appl Physiol (1985). 2009 Jan;106(1):326-32
pubmed: 19036896
Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1505-13
pubmed: 24855056
Diabetol Metab Syndr. 2019 Apr 30;11:33
pubmed: 31061679
FEBS Lett. 1999 Jan 29;443(3):285-9
pubmed: 10025949
J Clin Invest. 2001 Oct;108(8):1167-74
pubmed: 11602624
J Cell Physiol. 2010 Mar;222(3):669-75
pubmed: 19950211
Circ Res. 2010 Apr 30;106(8):1319-31
pubmed: 20431074
Chem Biol Interact. 2011 May 30;191(1-3):339-45
pubmed: 21334316
Diabetes. 1999 Feb;48(2):353-7
pubmed: 10334313
Circulation. 2006 Apr 18;113(15):1888-904
pubmed: 16618833
Circ Res. 2013 Apr 12;112(8):1171-88
pubmed: 23580773
J Biol Chem. 2009 Oct 9;284(41):28128-36
pubmed: 19666465
Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E759-66
pubmed: 19602584
Eur J Biochem. 1995 Apr 15;229(2):558-65
pubmed: 7744080
J Clin Invest. 2015 Oct 26;125(12):4514-28
pubmed: 26517696
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H875-82
pubmed: 12730050
Diabetes. 2006 Feb;55(2):496-505
pubmed: 16443786
J Hypertens. 2006 Aug;24(8):1655-61
pubmed: 16877970
Metabolism. 2007 Mar;56(3):308-13
pubmed: 17292717
Eur J Pharmacol. 2010 Feb 10;627(1-3):42-8
pubmed: 19878672
Am J Physiol. 1996 Nov;271(5 Pt 1):C1424-37
pubmed: 8944624
Antioxid Redox Signal. 2016 Jul 10;25(2):108-15
pubmed: 27043041
Diabetes Metab. 2013 May;39(3):179-90
pubmed: 23528671
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2653-8
pubmed: 16477035
Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2292-301
pubmed: 17673705
Heart. 2001 Oct;86(4):368-72
pubmed: 11559670
J Cardiovasc Pharmacol. 1996 Nov;28(5):703-11
pubmed: 8945685
Diabetes Care. 2019 Oct;42(10):1946-1955
pubmed: 30796109
Mol Cell Biol. 2006 Aug;26(16):5933-45
pubmed: 16880506
J Lipid Res. 2009 Apr;50 Suppl:S335-9
pubmed: 19029122
Diabetologia. 2017 Sep;60(9):1577-1585
pubmed: 28776086
Curr Opin Lipidol. 2005 Oct;16(5):507-11
pubmed: 16148534
Aging Cell. 2016 Jun;15(3):416-27
pubmed: 26890602
Diabetes. 2000 Nov;49(11):1939-45
pubmed: 11078463
Diabetes Metab Res Rev. 2002 Mar-Apr;18(2):156-9
pubmed: 11994908
Postgrad Med. 2017 Nov;129(8):811-821
pubmed: 28749197
J Basic Clin Physiol Pharmacol. 2007;18(2):129-40
pubmed: 17715568
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):17018-23
pubmed: 17075048
Planta Med. 2015 Aug;81(12-13):975-94
pubmed: 26132858
J Am Coll Cardiol. 2004 Feb 18;43(4):629-34
pubmed: 14975474
Cell Mol Life Sci. 2013 Aug;70(16):2859-72
pubmed: 23124189
Basic Clin Pharmacol Toxicol. 2020 Aug;127(2):81-91
pubmed: 31671245
Br J Pharmacol. 2002 May;136(2):255-63
pubmed: 12010774
Biochem Biophys Res Commun. 2010 May 28;396(2):199-205
pubmed: 20398632
Diabetes Metab Res Rev. 2006 Jul-Aug;22(4):323-30
pubmed: 16444763
J Exp Med. 2008 Sep 29;205(10):2409-17
pubmed: 18809715
J Intern Med. 2005 Sep;258(3):250-6
pubmed: 16115299
Pflugers Arch. 2010 May;459(6):995-1004
pubmed: 20127126
Diabetes Care. 2016 Feb;39(2):198-205
pubmed: 26285584
Eur J Biochem. 2004 Dec;271(23-24):4745-52
pubmed: 15606761
Nitric Oxide. 2016 May 1;55-56:45-53
pubmed: 26989010
Diabetes. 2009 Oct;58(10):2246-57
pubmed: 19592618
Apoptosis. 2007 May;12(5):841-55
pubmed: 17453156
Ann Intern Med. 2012 Nov 6;157(9):601-10
pubmed: 23128859
Diabetes. 2002 Jan;51(1):139-43
pubmed: 11756333
Br J Pharmacol. 2011 May;163(2):424-37
pubmed: 21250975
J Pharmacol Exp Ther. 2016 Feb;356(2):314-23
pubmed: 26582729
Circ Res. 2017 Feb 17;120(4):713-735
pubmed: 28209797
Prog Cardiovasc Dis. 2015 Mar-Apr;57(5):497-509
pubmed: 25460848
Biochem Biophys Res Commun. 2020 Feb 19;522(4):838-844
pubmed: 31801667
Nephrol Dial Transplant. 2018 Nov 1;33(11):1942-1949
pubmed: 29509925
J Clin Invest. 1992 Nov;90(5):2092-6
pubmed: 1385480
Atherosclerosis. 2014 Jan;232(1):156-64
pubmed: 24401231
J Clin Invest. 2002 Mar;109(6):817-26
pubmed: 11901190
Diabetes. 2003 Nov;52(11):2795-804
pubmed: 14578299
Metabolism. 1999 Nov;48(11):1346-50
pubmed: 10582539
Biochem Biophys Res Commun. 2010 Aug 6;398(4):735-40
pubmed: 20627091
J Pharmacol Exp Ther. 2011 Jun;337(3):591-9
pubmed: 21357660
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):3161-6
pubmed: 23382195
Ageing Res Rev. 2017 Nov;40:31-44
pubmed: 28802803
Respir Res. 2016 Aug 30;17(1):107
pubmed: 27576730
Cardiovasc Diabetol. 2017 Apr 11;16(1):47
pubmed: 28399917
Horm Metab Res. 2006 Nov;38(11):732-9
pubmed: 17111300
Arterioscler Thromb Vasc Biol. 2005 Dec;25(12):2488-94
pubmed: 16224049
Circ Res. 2002 Jun 28;90(12):1290-8
pubmed: 12089067
Diabetes. 2010 Jun;59(6):1386-96
pubmed: 20299472
Curr Med Chem. 2019;26(9):1693-1700
pubmed: 29737246
Pharmacol Rev. 1998 Mar;50(1):21-33
pubmed: 9549756
Nature. 2001 Dec 13;414(6865):813-20
pubmed: 11742414
BMJ. 2007 Sep 8;335(7618):497
pubmed: 17761999
Cardiovasc Ther. 2018 Aug;36(4):e12436
pubmed: 29797660
N Engl J Med. 1998 Jul 23;339(4):229-34
pubmed: 9673301
J Mol Cell Cardiol. 2011 Dec;51(6):885-93
pubmed: 21839087
Trends Biochem Sci. 2016 Jul;41(7):568-577
pubmed: 27180143
Cell Metab. 2015 Feb 3;21(2):159-162
pubmed: 25651170
Expert Opin Investig Drugs. 2012 Aug;21(8):1155-67
pubmed: 22694351
Diabetologia. 2017 Sep;60(9):1620-1629
pubmed: 28770324
Lancet. 1998 Sep 12;352(9131):854-65
pubmed: 9742977
Antioxid Redox Signal. 2011 Feb 1;14(3):439-57
pubmed: 20518704
Circulation. 2006 Apr 4;113(13):1708-14
pubmed: 16585403
Arch Intern Med. 2008 Oct 27;168(19):2070-80
pubmed: 18955635
Biochem Biophys Res Commun. 1997 Aug 18;237(2):340-4
pubmed: 9268712
Diabetes. 2005 Jul;54(7):2179-87
pubmed: 15983220
Basic Res Cardiol. 2008 May;103(3):274-84
pubmed: 18080084
Mol Cell. 2017 Jun 15;66(6):789-800
pubmed: 28622524
Diab Vasc Dis Res. 2012 Jan;9(1):52-8
pubmed: 22049096
Nature. 2014 Jun 26;510(7506):542-6
pubmed: 24847880
Diabetes. 2018 Dec;67(12):2554-2568
pubmed: 30257973
J Diabetes Res. 2018 Oct 4;2018:3106056
pubmed: 30402502
Free Radic Biol Med. 2014 May;70:117-28
pubmed: 24561578
Oncotarget. 2016 Mar 8;7(10):10773-87
pubmed: 26885898
J Clin Invest. 1996 Aug 15;98(4):894-8
pubmed: 8770859
J Clin Invest. 2001 Nov;108(9):1341-8
pubmed: 11696579
Genes Dev. 2011 Sep 15;25(18):1895-908
pubmed: 21937710
J Am Heart Assoc. 2014 Dec;3(6):e001202
pubmed: 25527624
J Am Coll Cardiol. 2001 Apr;37(5):1344-50
pubmed: 11300445
Mol Biol Rep. 2012 Apr;39(4):4509-18
pubmed: 21952822
Am J Physiol Heart Circ Physiol. 2008 Sep;295(3):H1165-H1176
pubmed: 18641273
Int J Mol Med. 2018 Mar;41(3):1365-1376
pubmed: 29286156
Mol Cell Biol. 2012 Jan;32(2):309-19
pubmed: 22083962
Pharmaceuticals (Basel). 2020 Sep 04;13(9):
pubmed: 32899806
Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):251-62
pubmed: 22436748
Apoptosis. 2008 Nov;13(11):1331-43
pubmed: 18780185
J Diabetes. 2017 May;9(5):434-449
pubmed: 28044409
Cardiovasc Diabetol. 2019 Apr 27;18(1):54
pubmed: 31029144
J Am Coll Cardiol. 1999 Jul;34(1):146-54
pubmed: 10400004
J Biochem Mol Toxicol. 2019 Sep;33(9):e22368
pubmed: 31332900
Hypertension. 2006 Jun;47(6):1183-8
pubmed: 16636195
Arch Intern Med. 2010 Nov 22;170(21):1892-9
pubmed: 21098347
J Clin Invest. 1997 Sep 1;100(5):1230-9
pubmed: 9276741
Diabetes. 2012 Jun;61(6):1423-33
pubmed: 22492524
Drug Saf. 2019 Dec;42(12):1449-1469
pubmed: 31372935
J Biol Chem. 2019 Sep 6;294(36):13525
pubmed: 31492733
Nutr Metab Cardiovasc Dis. 2007 May;17(4):274-9
pubmed: 17134952
Cell Signal. 2006 Mar;18(3):391-9
pubmed: 15970429
Med Princ Pract. 2015;24(5):401-15
pubmed: 26021280
Endocrinology. 2009 Jan;150(1):63-74
pubmed: 18772236
Am J Transl Res. 2016 May 15;8(5):2169-78
pubmed: 27347324
Biochem Pharmacol. 2015 Dec 1;98(3):412-21
pubmed: 26467186
Nat Cell Biol. 2011 Sep 02;13(9):1016-23
pubmed: 21892142
Circ Res. 2010 Apr 2;106(6):1117-28
pubmed: 20167927
Arch Physiol Biochem. 2019 Jun 1;:1-10
pubmed: 31155970
Diabetes. 2009 Aug;58(8):1893-901
pubmed: 19528375
Diabetologia. 2017 Sep;60(9):1566-1576
pubmed: 28776081
Br J Pharmacol. 2014 Jan;171(2):523-35
pubmed: 24372553
Curr Opin Lipidol. 2018 Aug;29(4):346-353
pubmed: 29878903
J Clin Endocrinol Metab. 2011 Apr;96(4):1015-20
pubmed: 21239513
Circ Res. 1983 Mar;52(3):352-7
pubmed: 6297832
J Intern Med. 2014 Jan;275(1):59-70
pubmed: 23981104
Nat Rev Mol Cell Biol. 2010 Dec;11(12):872-84
pubmed: 21102612
Circ Res. 2016 May 27;118(11):1808-29
pubmed: 27230643
J Diabetes Complications. 2016 Aug;30(6):1017-24
pubmed: 27217019
Mini Rev Med Chem. 2015;15(4):338-50
pubmed: 25723463
J Nephropharmacol. 2015 Jan 01;4(1):31-36
pubmed: 28197472
Biomed Pharmacother. 2010 Jan;64(1):35-43
pubmed: 19766439
Nat Rev Drug Discov. 2005 May;4(5):421-40
pubmed: 15864271
Front Pharmacol. 2012 May 09;3:87
pubmed: 22582044
Circulation. 2011 Jul 26;124(4):444-53
pubmed: 21747057
Cell Metab. 2012 Feb 8;15(2):186-200
pubmed: 22326220
Diabetologia. 1998 May;41(5):569-76
pubmed: 9628275
Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2439-44
pubmed: 16946131
Diabetes. 2017 Jan;66(1):193-205
pubmed: 27737949
Clin Sci (Lond). 2012 Mar;122(6):253-70
pubmed: 22117616
Circulation. 2012 Aug 7;126(6):729-40
pubmed: 22753194
Circulation. 2001 Nov 27;104(22):2673-8
pubmed: 11723017
Curr Diabetes Rev. 2019;15(4):328-339
pubmed: 30306875
Int Rev Cytol. 2003;224:29-55
pubmed: 12722948
Diabetes Care. 1996 Sep;19(9):934-9
pubmed: 8875085
Diabetes. 2012 Jan;61(1):217-28
pubmed: 22124463
Circulation. 2007 Aug 21;116(8):944-53
pubmed: 17679617
Curr Opin Pharmacol. 2019 Apr;45:1-7
pubmed: 30502742
Horm Metab Res. 2001 Jul;33(7):428-31
pubmed: 11507681
Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1115-1128
pubmed: 29366775
Cell Metab. 2005 Jul;2(1):9-19
pubmed: 16054095
Nat Rev Mol Cell Biol. 2018 Feb;19(2):121-135
pubmed: 28974774
Sci Rep. 2014 Jul 01;4:5519
pubmed: 24980430
Cardiovasc Diabetol. 2007 Oct 30;6:35
pubmed: 17971205
Diabetologia. 2004 Oct;47(10):1727-34
pubmed: 15490108
Exp Ther Med. 2017 Feb;13(2):794
pubmed: 28352368
Diabetes. 2006 Jun;55(6):1660-5
pubmed: 16731828
Pharmacol Res. 2014 Nov;89:19-28
pubmed: 25108154
Antioxid Redox Signal. 2017 Dec 10;27(17):1439-1445
pubmed: 28467723
Diabetes Care. 2010 Jan;33(1):49-54
pubmed: 19808929
Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):830-6
pubmed: 24482374
J Med Chem. 2017 Sep 14;60(17):7213-7232
pubmed: 28482155
Biomed Pharmacother. 2018 Feb;98:149-156
pubmed: 29253762
Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14855-60
pubmed: 17785417
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3329-35
pubmed: 14985505
Clin Exp Pharmacol Physiol. 2008 May;35(5-6):535-45
pubmed: 18177481
J Atheroscler Thromb. 2012;19(12):1083-92
pubmed: 22863784
J Diabetes Complications. 2013 Sep-Oct;27(5):501-7
pubmed: 23891275
Acta Physiol (Oxf). 2017 Jan;219(1):138-151
pubmed: 26680745
Diabetes. 1996 Apr;45(4):471-7
pubmed: 8603769
Nat Rev Endocrinol. 2019 Oct;15(10):569-589
pubmed: 31439934
Cardiovasc Diabetol. 2010 Sep 16;9:54
pubmed: 20843380
J Clin Endocrinol Metab. 1996 Feb;81(2):713-8
pubmed: 8636293
Diabetes Care. 2006 May;29(5):1083-9
pubmed: 16644641
Circ Res. 2016 Feb 19;118(4):620-36
pubmed: 26892962
J Biol Chem. 2011 Jan 7;286(1):1-11
pubmed: 21059655
Circulation. 1998 May 5;97(17):1695-701
pubmed: 9591763
Biochem Biophys Res Commun. 2015 Sep 11;465(1):41-6
pubmed: 26225747
Diabetes Obes Metab. 2013 May;15(5):427-31
pubmed: 23167274
Oncotarget. 2016 Jan 26;7(4):4265-78
pubmed: 26673006
Metabolism. 2005 Jun;54(6):829-34
pubmed: 15931622
Eur J Pharmacol. 2020 Oct 5;884:173349
pubmed: 32650008
Hypertension. 2000 Jan;35(1 Pt 1):108-12
pubmed: 10642283
Autophagy. 2019 May;15(5):843-870
pubmed: 30653446
Diabetes Res Clin Pract. 2010 Jul;89(1):38-45
pubmed: 20398956
J Am Soc Nephrol. 2000 Oct;11(10):1819-25
pubmed: 11004212
Br J Pharmacol. 2003 Oct;140(4):701-6
pubmed: 14534153
PLoS One. 2016 Mar 17;11(3):e0151845
pubmed: 26986624
Physiol Rev. 2013 Jan;93(1):137-88
pubmed: 23303908