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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Review Article

Antidiabetic Effects of Genistein: Mechanism of Action

Author(s): Ebrahim Abbasi and Iraj Khodadadi*

Volume 23, Issue 13, 2023

Published on: 12 July, 2023

Page: [1599 - 1610] Pages: 12

DOI: 10.2174/1871530323666230516103420

Price: $65

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Abstract

Diabetes mellitus is a metabolic disease recognized by abnormal glucose level due to defects in insulin action, insulin secretion, or both. Administration of soybean and isoflavones are accompanied by a lower risk of diabetes. The present review analyzed the previous published papers related to genistein. This isoflavone, which has been used for the prevention of some chronic diseases can inhibit hepatic glucose production, increase β-cell proliferation, reduce β-cell apoptosis, and show potential antioxidant and anti-diabetic effects. Therefore, genistein may be useful in the management of diabetes. The beneficial effects of this isoflavone on metabolic syndrome, diabetes, cardiovascular disease, osteoporosis, and cancer have been reported in animal and human studies. Moreover, genistein reduces hepatic glucose production, normalizes hyperglycemia, and gut microbiota and exhibits potential anti-oxidative, anti-apoptotic, and hypolipidemic effects. However, studies on the underlying mechanisms of the action of genistein are very limited. Therefore, the present study reviews multifaceted aspects of genistein to reveal a possible anti-diabetic mechanism of this agent. Genistein by regulating several signaling pathways can be used for the prevention and management of diabetes.

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[1]
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011; 94(3): 311-21.
[http://dx.doi.org/10.1016/j.diabres.2011.10.029] [PMID: 22079683]
[2]
Ye YB, Chen AL, Lu W, et al. Daidzein and genistein fail to improve glycemic control and insulin sensitivity in Chinese women with impaired glucose regulation: A double‐blind, randomized, placebo‐controlled trial. Mol Nutr Food Res 2015; 59(2): 240-9.
[http://dx.doi.org/10.1002/mnfr.201400390] [PMID: 25351561]
[3]
El-Kordy EA, Alshahrani AM. Effect of genistein, a natural soy isoflavone, on pancreatic β-cells of streptozotocin-induced diabetic rats: Histological and immunohistochemical study. J Microsc Ultrastruct 2015; 3(3): 108-19.
[http://dx.doi.org/10.1016/j.jmau.2015.03.005] [PMID: 30023190]
[4]
Fuloria S, Yusri MAA, Sekar M, et al. Genistein: A potential natural lead molecule for new drug design and development for treating memory impairment. Molecules 2022; 27(1): 265.
[http://dx.doi.org/10.3390/molecules27010265] [PMID: 35011497]
[5]
Kassaee SM, Goodarzi MT, Oshaghi EA. Antioxidant, antiglycation and anti-hyperlipidemic effects of Trigonella foenum and Cinnamon in type 2 diabetic rats. Jundishapur J Nat Pharm Prod 2018; 13(1)
[6]
Abbasi-Oshaghi E, Khodadadi I, Tavilani H, Mirzaei F, Goodarzi MT. Dill-normalized liver lipid accumulation, oxidative stress, and low-density lipoprotein receptor levels in high cholesterol fed hamsters. ARYA Atheroscler 2018; 14(5): 218-24.
[PMID: 30783412]
[7]
Abbasi-Oshaghi E, Khodadadi I, Mirzaei F, Ahmadi M, Tayebinia H, Goodarzi MT. Anethum graveolens L‎. Alleviates sperm ‎damage by limiting oxidative stress ‎and insulin ‎resistance ‎in ‎diabetic rats ‎. Open Med Chem J 2020; 14(1): 35-44.
[http://dx.doi.org/10.2174/1874104502014010035]
[8]
Incir S, Bolayirli IM, Inan O. Aydın, M.S.; Bilgin, I.A.; Sayan, I.; Esrefoglu, M.; Seven, A. The effects of genistein supplementation on fructose induced insulin resistance, oxidative stress and inflammation. Life Sci 2016; 158: 57-62.
[http://dx.doi.org/10.1016/j.lfs.2016.06.014] [PMID: 27350161]
[9]
Zang Y, Igarashi K, Yu C. Anti-obese and anti-diabetic effects of a mixture of daidzin and glycitin on C57BL/6J mice fed with a high-fat diet. Biosci Biotechnol Biochem 2015; 79(1): 117-23.
[http://dx.doi.org/10.1080/09168451.2014.955453] [PMID: 25209298]
[10]
González S, Jayagopal V, Kilpatrick ES, Chapman T, Atkin SL. Effects of isoflavone dietary supplementation on cardiovascular risk factors in type 2 diabetes. Diabetes Care 2007; 30(7): 1871-3.
[http://dx.doi.org/10.2337/dc06-1814] [PMID: 17468359]
[11]
Behloul N, Wu G. Genistein: A promising therapeutic agent for obesity and diabetes treatment. Eur J Pharmacol 2013; 698(1-3): 31-8.
[http://dx.doi.org/10.1016/j.ejphar.2012.11.013] [PMID: 23178528]
[12]
Yang Z, Kulkarni K, Zhu W, Hu M. Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME. Anticancer Agents Med Chem 2012; 12(10): 1264-80.
[http://dx.doi.org/10.2174/187152012803833107] [PMID: 22583407]
[13]
Chen J, Lin H, Hu M. Metabolism of flavonoids via enteric recycling: Role of intestinal disposition. J Pharmacol Exp Ther 2003; 304(3): 1228-35.
[http://dx.doi.org/10.1124/jpet.102.046409] [PMID: 12604700]
[14]
Rahman MMA, Hongsprabhas P. Genistein as antioxidant and antibrowning agents in in vivo and in vitro: A review. Biomed Pharmacother 2016; 82: 379-92.
[http://dx.doi.org/10.1016/j.biopha.2016.05.023] [PMID: 27470376]
[15]
Yang Z, Zhu W, Gao S, et al. Simultaneous determination of genistein and its four phase II metabolites in blood by a sensitive and robust UPLC–MS/MS method: Application to an oral bioavailability study of genistein in mice. J Pharm Biomed Anal 2010; 53(1): 81-9.
[http://dx.doi.org/10.1016/j.jpba.2010.03.011] [PMID: 20378296]
[16]
Ariyani W, Miyazaki W, Amano I, Hanamura K, Shirao T, Koibuchi N. Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway. Front Endocrinol 2020; 11: 554941.
[http://dx.doi.org/10.3389/fendo.2020.554941] [PMID: 33250856]
[17]
Murota K, Shimizu S, Miyamoto S, et al. Unique uptake and transport of isoflavone aglycones by human intestinal caco-2 cells: comparison of isoflavonoids and flavonoids. J Nutr 2002; 132(7): 1956-61.
[http://dx.doi.org/10.1093/jn/132.7.1956] [PMID: 12097676]
[18]
Sohel M, Biswas P, Al Amin M, et al. Genistein, a potential phytochemical against breast cancer treatment-insight into the molecular mechanisms. Processes 2022; 10(2): 415.
[http://dx.doi.org/10.3390/pr10020415]
[19]
Kim IS. Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans. Antioxidants 2021; 10(7): 1064.
[http://dx.doi.org/10.3390/antiox10071064] [PMID: 34209224]
[20]
Zhou L, Xiao X, Zhang Q, et al. Improved glucose and lipid metabolism in the early life of female offspring by maternal dietary genistein is associated with alterations in the gut microbiota. Front Endocrinol 2018; 9: 516.
[http://dx.doi.org/10.3389/fendo.2018.00516] [PMID: 30233500]
[21]
Zamani-Garmsiri F, Emamgholipour S, Rahmani FS, Ghasempour G, Jahangard AR, Meshkani R. Polyphenols: Potential anti-inflammatory agents for treatment of metabolic disorders. Phytother Res 2022; 36(1): 415-32.
[22]
Shafiee G, Saidijam M, Tavilani H, Ghasemkhani N, Khodadadi I. Genistein induces apoptosis and inhibits proliferation of HT29 colon cancer cells. Int J Mol Cell Med 2016; 5(3): 178-91.
[PMID: 27942504]
[23]
Shafiee G, Saidijam M, Tayebinia H, Khodadadi I. Beneficial effects of genistein in suppression of proliferation, inhibition of metastasis, and induction of apoptosis in PC3 prostate cancer cells. Arch Physiol Biochem 2020; 128(3): 694-702.
[PMID: 31985311]
[24]
Khodadadi I, Ghasemkhani N, Shafiee GR. Inhibition of gastric cancer cell growth and proliferation by genistein. J Adv Med Biomed Res 2018; 26(116): 88-99.
[25]
Fang K, Dong H, Wang D, Gong J, Huang W, Lu F. Soy isoflavones and glucose metabolism in menopausal women: A systematic review and meta-analysis of randomized controlled trials. Mol Nutr Food Res 2016; 60(7): 1602-14.
[http://dx.doi.org/10.1002/mnfr.201501024] [PMID: 27004555]
[26]
Zhang YB, Chen WH, Guo JJ, et al. Soy isoflavone supplementation could reduce body weight and improve glucose metabolism in non-Asian postmenopausal women—A meta-analysis. Nutrition 2013; 29(1): 8-14.
[http://dx.doi.org/10.1016/j.nut.2012.03.019] [PMID: 22858192]
[27]
Guevara-Cruz M, Godinez-Salas ET, Sanchez-Tapia M, Torres-Villalobos G, Pichardo-Ontiveros E, Guizar-Heredia R. Genistein stimulates insulin sensitivity through gut microbiota reshaping and skeletal muscle AMPK activation in obese subjects. BMJ Open Diabetes Res Care 2020; 8(1): e000948.
[http://dx.doi.org/10.1136/bmjdrc-2019-000948]
[28]
Hogh KLN, Craig MN, Uy CE, et al. Orešič M.; Gray, S.L. Overexpression of PPARγ specifically in pancreatic β-cells exacerbates obesity-induced glucose intolerance, reduces β-cell mass, and alters islet lipid metabolism in male mice. Endocrinology 2014; 155(10): 3843-52.
[http://dx.doi.org/10.1210/en.2014-1076] [PMID: 25051434]
[29]
Liu D, Zhen W, Yang Z, Carter JD, Si H, Reynolds KA. Genistein acutely stimulates insulin secretion in pancreatic beta-cells through a cAMP-dependent protein kinase pathway. Diabetes 2006; 55(4): 1043-50.
[http://dx.doi.org/10.2337/diabetes.55.04.06.db05-1089] [PMID: 16567527]
[30]
Fu Z, Zhang W, Zhen W, et al. Genistein induces pancreatic beta-cell proliferation through activation of multiple signaling pathways and prevents insulin-deficient diabetes in mice. Endocrinology 2010; 151(7): 3026-37.
[http://dx.doi.org/10.1210/en.2009-1294] [PMID: 20484465]
[31]
Sharma G, Prossnitz ER. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells. Endocrinology 2011; 152(8): 3030-9.
[http://dx.doi.org/10.1210/en.2011-0091] [PMID: 21673097]
[32]
Yousefi H, Karimi P, Alihemmati A, Alipour MR, Habibi P, Ahmadiasl N. Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis. Iran J Basic Med Sci 2017; 20(9): 1009-15.
[PMID: 29085595]
[33]
Gilbert ER, Liu D. Anti-diabetic functions of soy isoflavone genistein: mechanisms underlying its effects on pancreatic β-cell function. Food Funct 2013; 4(2): 200-12.
[http://dx.doi.org/10.1039/C2FO30199G] [PMID: 23160185]
[34]
Ohno T, Kato N, Ishii C, et al. Genistein augments cyclic adenosine 3‘5’-monophosphate(cAMP) accumulation and insulin release in MIN6 cells. Endocr Res 1993; 19(4): 273-85.
[http://dx.doi.org/10.1080/07435809309026682] [PMID: 7508378]
[35]
Lee SJ, Kim HE, Choi SE, et al. Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced potentiation of leucine/glutamine-stimulated insulin secretion. Mol Cells 2009; 28(3): 167-74.
[http://dx.doi.org/10.1007/s10059-009-0119-7] [PMID: 19756396]
[36]
Thomas P, Dong J. Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: A potential novel mechanism of endocrine disruption. J Steroid Biochem Mol Biol 2006; 102(1-5): 175-9.
[http://dx.doi.org/10.1016/j.jsbmb.2006.09.017] [PMID: 17088055]
[37]
Luo J, Wang A, Zhen W, et al. Phytonutrient genistein is a survival factor for pancreatic β-cells via GPR30-mediated mechanism. J Nutr Biochem 2018; 58: 59-70.
[http://dx.doi.org/10.1016/j.jnutbio.2018.04.018] [PMID: 29885598]
[38]
Mårtensson UEA, Salehi SA, Windahl S, et al. Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice. Endocrinology 2009; 150(2): 687-98.
[http://dx.doi.org/10.1210/en.2008-0623] [PMID: 18845638]
[39]
Liu S, Le May C, Wong WPS, et al. Importance of extranuclear estrogen receptor-alpha and membrane G protein-coupled estrogen receptor in pancreatic islet survival. Diabetes 2009; 58(10): 2292-302.
[http://dx.doi.org/10.2337/db09-0257] [PMID: 19587358]
[40]
Thangavel P, Puga-Olguín A. Genistein as potential therapeutic candidate for menopausal symptoms and other related diseases. Molecules 2019; 24(21): 3892.
[http://dx.doi.org/10.3390/molecules24213892]
[41]
Dkhar B, Khongsti K, Thabah D, Syiem D, Satyamoorthy K. Das, B Genistein represses PEPCK-C expression in an insulin-independent manner in HepG2 cells and in alloxan-induced diabetic mice. J Cell Biochem 2018; 119(2): 1953-70.
[http://dx.doi.org/10.1002/jcb.26356]
[42]
Pabich M, Materska M. Biological effect of soy isoflavones in the prevention of civilization diseases. Nutrients 2019; 11(7): 1660.
[http://dx.doi.org/10.3390/nu11071660]
[43]
Piro S, Anello M, Di Pietro C, et al. Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: Possible role of oxidative stress. Metabolism 2002; 51(10): 1340-7.
[http://dx.doi.org/10.1053/meta.2002.35200] [PMID: 12370856]
[44]
Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: Importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol 2019; 317(3): C420-33.
[http://dx.doi.org/10.1152/ajpcell.00141.2019] [PMID: 31216193]
[45]
Burgos-Morón E, Abad-Jiménez Z, Marañón AM, et al. Relationship between oxidative stress, ER stress, and inflammation in type 2 diabetes: The battle continues. J Clin Med 2019; 8(9): 1385.
[http://dx.doi.org/10.3390/jcm8091385] [PMID: 31487953]
[46]
Ma X, Chen Z, Wang L, et al. The pathogenesis of diabetes mellitus by oxidative stress and inflammation: Its inhibition by berberine. Front Pharmacol 2018; 9: 782.
[http://dx.doi.org/10.3389/fphar.2018.00782] [PMID: 30100874]
[47]
Wang J, Wang H. Oxidative stress in pancreatic beta cell regeneration. Antioxidants and Prooxidants. Effects on Health and Aging 2017; 2017: 1930261.
[48]
Djuric Z, Chen G, Doerge DR, Heilbrun LK, Kucuk O. Effect of soy isoflavone supplementation on markers of oxidative stress in men and women. Cancer Lett 2001; 172(1): 1-6.
[http://dx.doi.org/10.1016/S0304-3835(01)00627-9] [PMID: 11595123]
[49]
Gopaul NK, Änggård EE, Mallet AI, Betteridge DJ, Wolff SP, Nourooz-Zadeh J. Plasma 8-epi-PGF 2α levels are elevated in individuals with non-insulin dependent diabetes mellitus. FEBS Lett 1995; 368(2): 225-9.
[http://dx.doi.org/10.1016/0014-5793(95)00649-T] [PMID: 7628610]
[50]
Ibrahim WH, Habib HM, Chow CK, Bruckner GG. Isoflavone-rich soy isolate reduces lipid peroxidation in mouse liver. Int J Vitam Nutr Res 2008; 78(45): 217-22.
[http://dx.doi.org/10.1024/0300-9831.78.45.217] [PMID: 19326345]
[51]
Yoon GA, Park S. Antioxidant action of soy isoflavones on oxidative stress and antioxidant enzyme activities in exercised rats. Nutr Res Pract 2014; 8(6): 618-24.
[http://dx.doi.org/10.4162/nrp.2014.8.6.618] [PMID: 25489400]
[52]
Ganai AA, Khan AA, Malik ZA, Farooqi H. Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating d-Galactosamine induced fulminant hepatic failure in Wistar rats. Toxicol Appl Pharmacol 2015; 283(2): 139-46.
[http://dx.doi.org/10.1016/j.taap.2015.01.012] [PMID: 25620059]
[53]
Ji G, Yang Q, Hao J, et al. Anti-inflammatory effect of genistein on non-alcoholic steatohepatitis rats induced by high fat diet and its potential mechanisms. Int Immunopharmacol 2011; 11(6): 762-8.
[http://dx.doi.org/10.1016/j.intimp.2011.01.036] [PMID: 21320636]
[54]
Fujimoto M, Shimizu N, Kunii K, Martyn JAJ, Ueki K, Kaneki M. A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese diabetic mice. Diabetes 2005; 54(5): 1340-8.
[http://dx.doi.org/10.2337/diabetes.54.5.1340] [PMID: 15855318]
[55]
Wang A, Liu D, Luo J, Suh K-S, Moore W. Alkhalidy, H Phytochemical genistein promotes pancreatic beta-cell survival and exerts anti-diabetic effect via GPR30-mediated mechanism (1045.44). FASEB J 2014; 28(S1): 1045-4.
[56]
Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci 2018; 14(11): 1483-96.
[http://dx.doi.org/10.7150/ijbs.27173] [PMID: 30263000]
[57]
Kim EK, Kwon KB, Song MY, et al. Genistein protects pancreatic β cells against cytokine-mediated toxicity. Mol Cell Endocrinol 2007; 278(1-2): 18-28.
[http://dx.doi.org/10.1016/j.mce.2007.08.003] [PMID: 17881116]
[58]
Corbett JA, McDaniel ML. Does nitric oxide mediate autoimmune destruction of beta-cells? Possible therapeutic interventions in IDDM. Diabetes 1992; 41(8): 897-903.
[http://dx.doi.org/10.2337/diab.41.8.897] [PMID: 1378415]
[59]
Winer DA, Luck H, Tsai S, Winer S. The intestinal immune system in obesity and insulin resistance. Cell Metab 2016; 23(3): 413-26.
[http://dx.doi.org/10.1016/j.cmet.2016.01.003] [PMID: 26853748]
[60]
Diamant M, Blaak EE, de Vos WM. Do nutrient-gut-microbiota interactions play a role in human obesity, insulin resistance and type 2 diabetes? Obes Rev 2011; 12(4): 272-81.
[http://dx.doi.org/10.1111/j.1467-789X.2010.00797.x] [PMID: 20804522]
[61]
Hartstra AV, Bouter KEC, Bäckhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care 2015; 38(1): 159-65.
[http://dx.doi.org/10.2337/dc14-0769] [PMID: 25538312]
[62]
Payne AN, Chassard C, Lacroix C. Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: Implications for host-microbe interactions contributing to obesity. Obes Rev 2012; 13(9): 799-809.
[http://dx.doi.org/10.1111/j.1467-789X.2012.01009.x] [PMID: 22686435]
[63]
Adeli K, Lewis GF. Intestinal lipoprotein overproduction in insulin-resistant states. Curr Opin Lipidol 2008; 19(3): 221-8.
[http://dx.doi.org/10.1097/MOL.0b013e3282ffaf82] [PMID: 18460911]
[64]
Lewis GF, Uffelman K, Naples M, Szeto L, Haidari M, Adeli K. Intestinal lipoprotein overproduction, a newly recognized component of insulin resistance, is ameliorated by the insulin sensitizer rosiglitazone: Studies in the fructose-fed Syrian golden hamster. Endocrinology 2005; 146(1): 247-55.
[http://dx.doi.org/10.1210/en.2004-1143] [PMID: 15486228]
[65]
Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: A review on its anti-inflammatory properties. Front Pharmacol 2022; 13: 820969.
[http://dx.doi.org/10.3389/fphar.2022.820969] [PMID: 35140617]
[66]
Yousefi H, Komaki A, Shahidi S, et al. Diabetic neovascularization defects in the retina are improved by genistein supplementation in the ovariectomized rat. Inflammopharmacology 2021; 29(5): 1579-86.
[http://dx.doi.org/10.1007/s10787-021-00852-5] [PMID: 34581950]
[67]
Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: How are they interlinked? J Biomed Sci 2016; 23(1): 87.
[http://dx.doi.org/10.1186/s12929-016-0303-y] [PMID: 27912756]
[68]
Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World J Diabetes 2020; 11(7): 293-308.
[http://dx.doi.org/10.4239/wjd.v11.i7.293] [PMID: 32843932]
[69]
Zaky A, Glastras SJ, Wong MYW, Pollock CA, Saad S. The role of the gut microbiome in diabetes and obesity-related kidney disease. Int J Mol Sci 2021; 22(17): 9641.
[http://dx.doi.org/10.3390/ijms22179641] [PMID: 34502562]
[70]
Saad MJA, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology 2016; 31(4): 283-93.
[http://dx.doi.org/10.1152/physiol.00041.2015] [PMID: 27252163]
[71]
Tremaroli V, Bäckhed F. Functional interactions between the gut microbiota and host metabolism. Nature 2012; 489(7415): 242-9.
[http://dx.doi.org/10.1038/nature11552] [PMID: 22972297]
[72]
Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med 2016; 8(1): 42.
[http://dx.doi.org/10.1186/s13073-016-0303-2] [PMID: 27098727]
[73]
Hwang I, Park YJ, Kim YR, et al. Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon‐like peptide 1 in diet‐induced obesity. FASEB J 2015; 29(6): 2397-411.
[http://dx.doi.org/10.1096/fj.14-265983] [PMID: 25713030]
[74]
Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: The hygiene hypothesis expanded? Diabetes Care 2010; 33(10): 2277-84.
[http://dx.doi.org/10.2337/dc10-0556] [PMID: 20876708]
[75]
Blaut M. Gut microbiota and energy balance: Role in obesity. Proc Nutr Soc 2015; 74(3): 227-34.
[http://dx.doi.org/10.1017/S0029665114001700] [PMID: 25518735]
[76]
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Human gut microbes associated with obesity. Nature 2006; 444(7122): 1022-3.
[http://dx.doi.org/10.1038/4441022a] [PMID: 17183309]
[77]
Everard A, Cani PD. Gut microbiota and GLP-1. Rev Endocr Metab Disord 2014; 15(3): 189-96.
[http://dx.doi.org/10.1007/s11154-014-9288-6] [PMID: 24789701]
[78]
Rehman K, Ali MB, Akash MSH. Genistein enhances the secretion of glucagon-like peptide-1 (GLP-1) via downregulation of inflammatory responses. Biomed Pharmacother 2019; 112: 108670.
[http://dx.doi.org/10.1016/j.biopha.2019.108670] [PMID: 30784939]
[79]
Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 2016; 535(7612): 376-81.
[http://dx.doi.org/10.1038/nature18646] [PMID: 27409811]
[80]
Medzhitov R, Horng T. Transcriptional control of the inflammatory response. Nat Rev Immunol 2009; 9(10): 692-703.
[http://dx.doi.org/10.1038/nri2634] [PMID: 19859064]
[81]
Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003; 21(1): 335-76.
[http://dx.doi.org/10.1146/annurev.immunol.21.120601.141126] [PMID: 12524386]
[82]
Caricilli A, Saad M. The role of gut microbiota on insulin resistance. Nutrients 2013; 5(3): 829-51.
[http://dx.doi.org/10.3390/nu5030829] [PMID: 23482058]
[83]
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid–induced insulin resistance. J Clin Invest 2006; 116(11): 3015-25.
[http://dx.doi.org/10.1172/JCI28898] [PMID: 17053832]
[84]
Ding S, Lund PK. Role of intestinal inflammation as an early event in obesity and insulin resistance. Curr Opin Clin Nutr Metab Care 2011; 14(4): 328-33.
[http://dx.doi.org/10.1097/MCO.0b013e3283478727] [PMID: 21587067]
[85]
Jain R, Bolch C, Al-Nakkash L, Sweazea KL. Systematic review of the impact of genistein on diabetes-related outcomes. Am J Physiol Regul Integr Comp Physiol 2022; 323(3): R279-88.
[http://dx.doi.org/10.1152/ajpregu.00236.2021] [PMID: 35816719]
[86]
Yang R, Jia Q, Mehmood S, Ma S, Liu X. Genistein ameliorates inflammation and insulin resistance through mediation of gut microbiota composition in type 2 diabetic mice. Eur J Nutr 2021; 60(4): 2155-68.
[http://dx.doi.org/10.1007/s00394-020-02403-0] [PMID: 33068158]
[87]
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577-85.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[88]
Suksri K, Semprasert N, Limjindaporn T, Yenchitsomanus P, Kooptiwoot S, Kooptiwut S. Cytoprotective effect of genistein against dexamethasone-induced pancreatic β-cell apoptosis. Sci Rep 2022; 12(1): 12950.
[http://dx.doi.org/10.1038/s41598-022-17372-z] [PMID: 35902739]
[89]
Lee JS. Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sci 2006; 79(16): 1578-84.
[http://dx.doi.org/10.1016/j.lfs.2006.06.030] [PMID: 16831449]
[90]
Fu Z, Gilbert ER, Pfeiffer L, Zhang Y, Fu Y, Liu D. Genistein ameliorates hyperglycemia in a mouse model of nongenetic type 2 diabetes. Appl Physiol Nutr Metab 2012; 37(3): 480-8.
[http://dx.doi.org/10.1139/h2012-005] [PMID: 22509809]
[91]
Bitto A, Altavilla D, Bonaiuto A, et al. Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome. J Endocrinol 2009; 200(3): 367-76.
[http://dx.doi.org/10.1677/JOE-08-0206] [PMID: 19066292]
[92]
Elmarakby AA, Ibrahim AS, Faulkner J, Mozaffari MS, Liou GI, Abdelsayed R. Tyrosine kinase inhibitor, genistein, reduces renal inflammation and injury in streptozotocin-induced diabetic mice. Vascul Pharmacol 2011; 55(5-6): 149-56.
[http://dx.doi.org/10.1016/j.vph.2011.07.007] [PMID: 21807121]
[93]
Choi MS, Jung UJ, Yeo J, Kim MJ, Lee MK. Genistein and daidzein prevent diabetes onset by elevating insulin level and altering hepatic gluconeogenic and lipogenic enzyme activities in non-obese diabetic (NOD) mice. Diabetes Metab Res Rev 2008; 24(1): 74-81.
[http://dx.doi.org/10.1002/dmrr.780] [PMID: 17932873]
[94]
Choi JS, Koh IU, Song J. Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats. Nutr Res 2012; 32(11): 844-55.
[http://dx.doi.org/10.1016/j.nutres.2012.10.002] [PMID: 23176795]
[95]
Yang W, Wang S, Li L, Liang Z, Wang L. Genistein reduces hyperglycemia and islet cell loss in a high-dosage manner in rats with alloxan-induced pancreatic damage. Pancreas 2011; 40(3): 396-402.
[http://dx.doi.org/10.1097/MPA.0b013e318204e74d] [PMID: 21206328]
[96]
Paradkar PN, Blum PS, Berhow MA, Baumann H, Kuo SM. Dietary isoflavones suppress endotoxin-induced inflammatory reaction in liver and intestine. Cancer Lett 2004; 215(1): 21-8.
[http://dx.doi.org/10.1016/j.canlet.2004.05.019] [PMID: 15374628]
[97]
Susutlertpanya W, Werawatganon D, Siriviriyakul P, Klaikeaw N. Genistein attenuates nonalcoholic steatohepatitis and increases hepatic PPAR γ in a rat model. Evid Based Complement Alternat Med 2015; 2015: 1-7.
[http://dx.doi.org/10.1155/2015/509057] [PMID: 26246839]
[98]
Javani G, Alihemmati A, Habibi P, et al. The effects of genistein on renal oxidative stress and inflammation of ovariectomized rats. Jundishapur J Nat Pharm Prod 2019; 14(4): e57149.
[http://dx.doi.org/10.5812/jjnpp.57149]
[99]
Yin Y, Liu H, Zheng Z, Lu R, Jiang Z. Genistein can ameliorate hepatic inflammatory reaction in nonalcoholic steatohepatitis rats. Biomed Pharmacother 2019; 111: 1290-6.
[http://dx.doi.org/10.1016/j.biopha.2019.01.004] [PMID: 30841442]
[100]
Palanisamy N, Viswanathan P, Anuradha CV. Effect of genistein, a soy isoflavone, on whole body insulin sensitivity and renal damage induced by a high-fructose diet. Ren Fail 2008; 30(6): 645-54.
[http://dx.doi.org/10.1080/08860220802134532] [PMID: 18661416]

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