title: Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications.
abstract: The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs.
authors.affiliation: Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland; and.
authors.forename: Kashif M
authors.initials: KM
authors.lastname: Munir
authors.forename: Sruti
authors.initials: S
authors.lastname: Chandrasekaran
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Quon
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D059808:Polyphenols
keywords: endothelial dysfunction; functional foods; insulin resistance; polyphenols
references.citation: Lipids. 1999 Jun;34(6):591-8
references.pmid: 10405973
references.citation: Circulation. 2002 Oct 1;106(14):1783-7
references.pmid: 12356630
references.citation: Biol Trace Elem Res. 2012 Dec;149(3):315-22
references.pmid: 22581111
references.citation: J Clin Invest. 1996 Aug 15;98(4):894-8
references.pmid: 8770859
references.citation: Am J Clin Nutr. 2008 Dec;88(6):1685-96
references.pmid: 19064532
references.citation: Int J Biochem Cell Biol. 2006;38(7):1134-45
references.pmid: 16427799
references.citation: Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H813-22
references.pmid: 15792994
references.citation: Ann Intern Med. 2006 Apr 18;144(8):554-62
references.pmid: 16618952
references.citation: Am J Physiol Endocrinol Metab. 2007 May;292(5):E1378-87
references.pmid: 17227956
references.citation: Diabetologia. 2002 May;45(5):623-34
references.pmid: 12107742
references.citation: Clin Nutr. 2011 Feb;30(1):38-43
references.pmid: 20655129
references.citation: Ann Intern Med. 2001 Jun 19;134(12):1106-14
references.pmid: 11412050
references.citation: Brain Res. 2011 Oct 28;1420:93-105
references.pmid: 21959178
references.citation: J Int Soc Sports Nutr. 2013 May 24;10:27
references.pmid: 23705637
references.citation: BMC Pharmacol. 2004 Aug 26;4:18
references.pmid: 15331020
references.citation: Mol Pharmacol. 2004 Jan;65(1):15-7
references.pmid: 14722232
references.citation: J Ethnopharmacol. 2002 Nov;83(1-2):109-16
references.pmid: 12413715
references.citation: J Nutr Biochem. 2012 Sep;23(9):1134-45
references.pmid: 22137262
references.citation: BMJ. 2012 May 30;344:e3657
references.pmid: 22653982
references.citation: J Clin Endocrinol Metab. 2011 May;96(5):E782-92
references.pmid: 21346065
references.citation: J Nutr Sci Vitaminol (Tokyo). 2004 Jun;50(3):211-8
references.pmid: 15386934
references.citation: Circulation. 2006 Apr 18;113(15):1888-904
references.pmid: 16618833
references.citation: Mol Nutr Food Res. 2013 Jun;57(6):974-85
references.pmid: 23456781
references.citation: Ann Intern Med. 1999 Aug 17;131(4):281-303
references.pmid: 10454950
references.citation: Am J Clin Nutr. 2007 Mar;85(3):895-909
references.pmid: 17344514
references.citation: J Biol Chem. 2007 May 4;282(18):13736-45
references.pmid: 17363366
references.citation: Am J Epidemiol. 2001 Sep 15;154(6):495-503
references.pmid: 11549554
references.citation: Curr Diab Rep. 2003 Aug;3(4):279-88
references.pmid: 12866989
references.citation: Diabetes. 2005 Aug;54(8):2415-23
references.pmid: 16046309
references.citation: J Biol Chem. 2008 Oct 24;283(43):29228-38
references.pmid: 18718910
references.citation: J Biol Chem. 2002 Jan 18;277(3):1794-9
references.pmid: 11707433
references.citation: Diabetes. 2002 Dec;51(12):3517-23
references.pmid: 12453909
references.citation: Endocrinology. 2010 Jan;151(1):103-14
references.pmid: 19887561
references.citation: J Nutr. 2011 Nov;141(11):1982-8
references.pmid: 21956956
references.citation: J Appl Physiol (1985). 2013 Apr;114(7):833
references.pmid: 23329822
references.citation: J Biol Chem. 2002 Sep 20;277(38):34933-40
references.pmid: 12118006
references.citation: Mol Cell Biochem. 2012 Nov;370(1-2):141-50
references.pmid: 22865466
references.citation: Nutrition. 2008 May;24(5):470-6
references.pmid: 18329851
references.citation: Cell Signal. 1999 Aug;11(8):563-74
references.pmid: 10433517
references.citation: Nutr Res. 2012 Jun;32(6):421-7
references.pmid: 22749178
references.citation: Endocrinol Metab Clin North Am. 2008 Sep;37(3):685-711, ix-x
references.pmid: 18775359
references.citation: J Hypertens. 2003 Dec;21(12):2281-6
references.pmid: 14654748
references.citation: Hypertension. 2002 Feb;39(2 Pt 2):508-12
references.pmid: 11882599
references.citation: J Clin Endocrinol Metab. 2005 Feb;90(2):1078-82
references.pmid: 15536160
references.citation: Nutr Metab (Lond). 2012 Feb 14;9:11
references.pmid: 22333133
references.citation: J Biol Chem. 1995 Feb 3;270(5):2036-40
references.pmid: 7836430
references.citation: Circulation. 2000 Apr 4;101(13):1539-45
references.pmid: 10747347
references.citation: Diabetes. 1995 Jun;44(6):705-17
references.pmid: 7789637
references.citation: J Am Coll Nutr. 2007 Apr;26(2):95-102
references.pmid: 17536120
references.citation: J Biol Chem. 2001 Aug 10;276(32):30392-8
references.pmid: 11402048
references.citation: Br J Nutr. 2004 Dec;92(6):963-72
references.pmid: 15613259
references.citation: Liver Transpl. 2006 Dec;12(12):1892-5
references.pmid: 17133573
references.citation: Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):523-30
references.pmid: 17563474
references.citation: Endocr Rev. 2007 Aug;28(5):463-91
references.pmid: 17525361
references.citation: Am J Clin Nutr. 2012 Mar;95(3):740-51
references.pmid: 22301923
references.citation: Lancet. 2006 Jan 28;367(9507):320-6
references.pmid: 16443039
references.citation: Arch Intern Med. 2006 Feb 27;166(4):411-7
references.pmid: 16505260
references.citation: Eur J Clin Nutr. 2003 Feb;57(2):235-42
references.pmid: 12571654
references.citation: J Physiol. 2011 Sep 15;589(Pt 18):4615-31
references.pmid: 21788351
references.citation: J Cardiovasc Pharmacol. 2006 Mar;47(3):385-90
references.pmid: 16633080
references.citation: Diabetologia. 1998 May;41(5):569-76
references.pmid: 9628275
references.citation: Eur J Clin Nutr. 2011 Aug;65(8):879-86
references.pmid: 21559039
references.citation: J Nutr Sci Vitaminol (Tokyo). 2008 Feb;54(1):95-8
references.pmid: 18388414
references.citation: J Clin Biochem Nutr. 2010 Jan;46(1):87-92
references.pmid: 20104270
references.citation: JAMA. 2006 Sep 13;296(10):1255-65
references.pmid: 16968850
references.citation: Phytother Res. 2003 May;17(5):477-80
references.pmid: 12748982
references.citation: PLoS One. 2011 Mar 04;6(3):e16974
references.pmid: 21394199
references.citation: Diabetes. 1988 Jun;37(6):667-87
references.pmid: 3289989
references.citation: Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E15-26
references.pmid: 17957034
references.citation: J Cardiovasc Pharmacol. 2011 Jan;57(1):44-50
references.pmid: 20966764
references.citation: Mol Endocrinol. 2002 Aug;16(8):1931-42
references.pmid: 12145346
references.citation: Diabetes. 1999 Apr;48(4):821-7
references.pmid: 10102699
references.citation: Biosci Biotechnol Biochem. 2009 Dec;73(12):2779-82
references.pmid: 19966469
references.citation: Am J Clin Nutr. 2011 Aug;94(2):601-10
references.pmid: 21715508
references.citation: Heart. 2004 Dec;90(12):1485-6
references.pmid: 15547040
references.citation: Nat Rev Cancer. 2009 Jun;9(6):429-39
references.pmid: 19472429
references.citation: JAMA. 1999 Oct 6;282(13):1233-9
references.pmid: 10517425
references.citation: J Nutr Biochem. 2001 Jan;12(1):14-20
references.pmid: 11179857
references.citation: J Am Diet Assoc. 2011 Nov;111(11):1720-9
references.pmid: 22027055
references.citation: J Biol Chem. 2007 Oct 12;282(41):30143-9
references.pmid: 17724029
references.citation: Circulation. 2007 Nov 20;116(21):2376-82
references.pmid: 17984375
references.citation: Eur Heart J. 2010 Jul;31(13):1616-23
references.pmid: 20354055
references.citation: J Clin Invest. 1990 Jun;85(6):1844-52
references.pmid: 2189893
references.citation: Clin Nutr. 2011 Apr;30(2):182-7
references.pmid: 20858571
references.citation: J Clin Invest. 1991 Apr;87(4):1186-94
references.pmid: 2010535
references.citation: Eur J Clin Pharmacol. 2009 Apr;65(4):331-41
references.pmid: 19198822
references.citation: J Nutr. 2011 Jun;141(6):1095-100
references.pmid: 21525262
references.citation: J Epidemiol. 2011;21(3):169-75
references.pmid: 21389640
references.citation: J Intern Med. 2009 Sep;266(3):248-57
references.pmid: 19711504
references.citation: J Med Food. 2008 Sep;11(3):429-34
references.pmid: 18800888
references.citation: Circulation. 1999 Aug 24;100(8):820-5
references.pmid: 10458717
references.citation: Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
references.pmid: 22187469
references.citation: Annu Rev Nutr. 2013;33:105-28
references.pmid: 23642199
references.citation: World J Cardiol. 2012 Jan 26;4(1):1-7
references.pmid: 22279598
references.citation: Diabetes. 2006 May;55(5):1436-42
references.pmid: 16644702
references.citation: J Nutr. 2008 Sep;138(9):1671-6
references.pmid: 18716168
references.citation: Heart Fail Clin. 2012 Oct;8(4):589-607
references.pmid: 22999242
references.citation: J Nutr Sci Vitaminol (Tokyo). 2005 Dec;51(6):460-70
references.pmid: 16521708
references.citation: J Chromatogr A. 2001 Aug 10;926(1):211-20
references.pmid: 11554414