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Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Research Article

Evaluation Effects of Quercetin on Streptozotocin-treated RINm5F Pancreatic β-cells in vitro

Author(s): Maryam Mazraesefidi , Maryam Mohammad Sadeghipour , Hossein Khorramdelazad , Mahdi Mahmoodi , Alireza Khoshdel , Mohammadali Fahmidehkar , Reza Hosseiniara * and Mohammad Reza Hajizadeh*

Volume 15, Issue 4, 2021

Page: [310 - 318] Pages: 9

DOI: 10.2174/2212796816666211223101206

Price: $65

Abstract

Background and objectives: Quercetin is a naturally occurring phenolic compound abundantly present in plants as a secondary metabolite. The purpose of this study was to investigate the effect of quercetin on improving RINm5F β-insulinemia cell viability, glucose-stimulated insulin secretion (GSIS), and cell insulin content in the presence or absence of streptozotocin (STZ).

Methods: This experimental study was conducted on RINm5F β-insulinemia cell line. The cell viability was evaluated by MTT assay. The necrosis was confirmed by flowcytometry and insulin ELISA kit was used to measure the GSIS level and cell insulin content. It should be noted that for testing of cells by 50μM of quercetin, simultaneous treatment and pre-treatment of quercetin were performed in the presence of STZ (20mM).

Results: The quercetin was able to improve the viability of RINm5F cells in the presence of STZ and to increase the GSIS level and cell insulin content under STZ and glucotoxic conditions.

Conclusion: The quercetin seems to have beneficial effects on β-cells, especially the synthesis and secretion of insulin. In addition to the therapeutic effect, given the low toxicity of this flavonoid and the results of this study, the quercetin as a preventive agent may play an important role in maintaining the health of β-cells in people at risk of diabetes.

Keywords: Quercetin, RINm5F, Diabetes Mellitus, Insulin, Streptozocin

Graphical Abstract

[1]
Bensellam M, Laybutt DR, Jonas J-C. The molecular mechanisms of pancreatic β-cell glucotoxicity: recent findings and future research directions. Mol Cell Endocrinol 2012; 364(1-2): 1-27.
[http://dx.doi.org/10.1016/j.mce.2012.08.003] [PMID: 22885162]
[2]
Belhadj S, Hentati O, Hamdaoui G, et al. Beneficial effect of jojoba seed extracts on hyperglycemia-induced oxidative stress in rinm5f beta cells. Nutrients 2018; 10(3): 384.
[http://dx.doi.org/10.3390/nu10030384] [PMID: 29558444]
[3]
Singh S, Usman K, Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World J Diabetes 2016; 7(15): 302-15.
[http://dx.doi.org/10.4239/wjd.v7.i15.302] [PMID: 27555891]
[4]
Babu PV, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem 2013; 24(11): 1777-89.
[http://dx.doi.org/10.1016/j.jnutbio.2013.06.003] [PMID: 24029069]
[5]
Soares JMD, Pereira Leal AEB, Silva JC, Almeida JRGS, de Oliveira HP. Influence of flavonoids on mechanism of modulation of insulin secretion. Pharmacogn Mag 2017; 13(52): 639-46.
[http://dx.doi.org/10.4103/pm.pm_87_17] [PMID: 29200726]
[6]
Inal ME, Akgün A, Kahraman A. Radioprotective effects of exogenous glutathione against whole-body γ-ray irradiation: age- and gender-related changes in malondialdehyde levels, superoxide dismutase and catalase activities in rat liver. Methods Find Exp Clin Pharmacol 2002; 24(4): 209-12.
[http://dx.doi.org/10.1358/mf.2002.24.4.678452] [PMID: 12092007]
[7]
Carrasco-Pozo C, Gotteland M, Castillo RL, Chen C. 3,4-Dihydroxyphenylacetic acid, a microbiota-derived metabolite of quercetin, protects against pancreatic β-cells dysfunction induced by high cholesterol. Exp Cell Res 2015; 334(2): 270-82.
[http://dx.doi.org/10.1016/j.yexcr.2015.03.021] [PMID: 25845496]
[8]
Sandeep MS, Nandini CD. Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats. Biomed Pharmacother 2017; 94: 605-11.
[http://dx.doi.org/10.1016/j.biopha.2017.07.142] [PMID: 28783583]
[9]
Chiş IC, Mureşan A, Oros A, Nagy AL, Clichici S. Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats. Physiol Int 2016; 103(1): 49-64.
[PMID: 27030627]
[10]
López LC, Varea O, Navarro S, et al. Benzbromarone, quercetin, and folic acid inhibit amylin aggregation. Int J Mol Sci 2016; 17(6): 964.
[http://dx.doi.org/10.3390/ijms17060964] [PMID: 27322259]
[11]
Suganya N, Dornadula S, Chatterjee S, Mohanram RK. Quercetin improves endothelial function in diabetic rats through inhibition of endoplasmic reticulum stress-mediated oxidative stress. Eur J Pharmacol 2018; 819: 80-8.
[http://dx.doi.org/10.1016/j.ejphar.2017.11.034] [PMID: 29169872]
[12]
Guo JH, Chen H, Ruan YC, et al. Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR. Nat Commun 2014; 5: 4420.
[http://dx.doi.org/10.1038/ncomms5420] [PMID: 25025956]
[13]
Yassin LS, Alberti A, Ferreira Zielinski AA, da Rosa Oliveira-Emilio H, Nogueira A Cytoprotective effect of phenolic extract from brazilian apple peel in insulin-producing cells. Curr Nutr Food Sci 2018; 14(2): 136-42.
[http://dx.doi.org/10.2174/1573401313666170427125753]
[14]
Chen J, Jeppesen PB, Nordentoft I, Hermansen K. Stevioside improves pancreatic β-cell function during glucotoxicity via regulation of acetyl-CoA carboxylase. Am J Physiol Endocrinol Metab 2007; 292(6): E1906-16.
[http://dx.doi.org/10.1152/ajpendo.00356.2006] [PMID: 17341549]
[15]
Lin P, Chen L, Li D, et al. Adiponectin reduces glucotoxicity-induced apoptosis of INS-1 rat insulin-secreting cells on a microfluidic chip. Tohoku J Exp Med 2009; 217(1): 59-65.
[http://dx.doi.org/10.1620/tjem.217.59] [PMID: 19155609]
[16]
Dall’Asta M, Bayle M, Neasta J, et al. Protection of pancreatic β- cell function by dietary polyphenols. Phytochem Rev 2015; 14(6): 933-59.
[http://dx.doi.org/10.1007/s11101-015-9429-x]
[17]
Youl E, Magous R, Cros G, Oiry C. MAP Kinase cross talks in oxidative stress-induced impairment of insulin secretion. Involvement in the protective activity of quercetin. Fundam Clin Pharmacol 2014; 28(6): 608-15.
[http://dx.doi.org/10.1111/fcp.12078] [PMID: 24702479]
[18]
Badolato M, Carullo G, Perri M, et al. Quercetin/oleic acid-based G-protein-coupled receptor 40 ligands as new insulin secretion modulators. Future Med Chem 2017; 9(16): 1873-85.
[http://dx.doi.org/10.4155/fmc-2017-0113] [PMID: 29064290]
[19]
Bathina S, Srinivas N, Das UN. BDNF protects pancreatic β cells (RIN5F) against cytotoxic action of alloxan, streptozotocin, doxorubicin and benzo(a)pyrene in vitro. Metabolism 2016; 65(5): 667-84.
[http://dx.doi.org/10.1016/j.metabol.2016.01.016] [PMID: 27085775]
[20]
Naijil G, Anju TR, Jayanarayanan S, Paulose CS. Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats. Nutr Res 2015; 35(9): 823-33.
[http://dx.doi.org/10.1016/j.nutres.2015.06.011] [PMID: 26255758]
[21]
Fernandez-Gomez B, Ramos S, Goya L, et al. Coffee silverskin extract improves glucose-stimulated insulin secretion and protects against streptozotocin-induced damage in pancreatic INS-1E beta cells 2016; 89: 1015-22.
[http://dx.doi.org/10.1016/j.foodres.2016.03.006]
[22]
Carrasco-Pozo C, Tan KN, Reyes-Farias M, et al. The deleterious effect of cholesterol and protection by quercetin on mitochondrial bioenergetics of pancreatic β-cells, glycemic control and inflammation: In vitro and in vivo studies. Redox Biol 2016; 9: 229-43.
[http://dx.doi.org/10.1016/j.redox.2016.08.007] [PMID: 27591402]
[23]
Arya A, Al-Obaidi MM, Shahid N, et al. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study. Food Chem Toxicol 2014; 71: 183-96.
[http://dx.doi.org/10.1016/j.fct.2014.06.010] [PMID: 24953551]
[24]
Kittl M, Beyreis M, Tumurkhuu M, et al. Quercetin stimulates insulin secretion and reduces the viability of rat INS-1 beta-cells. Cell Physiol Biochem 2016; 39(1): 278-93.
[http://dx.doi.org/10.1159/000445623] [PMID: 27336168]
[25]
Bhattacharya S, Oksbjerg N, Young JF, Jeppesen PB. Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells. Diabetes Obes Metab 2014; 16(7): 602-12.
[http://dx.doi.org/10.1111/dom.12236] [PMID: 24205999]
[26]
Cai EP, Lin JK. Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic beta cells. J Agric Food Chem 2009; 57(20): 9817-27.
[http://dx.doi.org/10.1021/jf902618v] [PMID: 19803520]
[27]
Zheng S, Zhao M, Ren Y, Wu Y, Yang J. Sesamin suppresses STZ induced INS-1 cell apoptosis through inhibition of NF-κB activation and regulation of Bcl-2 family protein expression. Eur J Pharmacol 2015; 750: 52-8.
[http://dx.doi.org/10.1016/j.ejphar.2015.01.031] [PMID: 25637086]
[28]
Youl E, Bardy G, Magous R, et al. Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway. Br J Pharmacol 2010; 161(4): 799-814.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00910.x] [PMID: 20860660]
[29]
Gerber PA, Rutter GA. The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus. Antioxid Redox Signal 2017; 26(10): 501-18.
[http://dx.doi.org/10.1089/ars.2016.6755] [PMID: 27225690]
[30]
Qureshi FM, Dejene EA, Corbin KL, Nunemaker CS. Stress-induced dissociations between intracellular calcium signaling and insulin secretion in pancreatic islets. Cell Calcium 2015; 57(5-6): 366-75.
[http://dx.doi.org/10.1016/j.ceca.2015.03.002] [PMID: 25861744]
[31]
Umamaheswari J, Subramanian SP. Zinc-silibinin complex ameliorates oxidative stress in high fat fed low dose STZ induced type 2 diabetes in rats. J Pharm Res 2015; 9(4): 288-98.
[32]
Wu C-H, Hsieh H-T, Lin J-A, Yen GC. Alternanthera paronychioides protects pancreatic β-cells from glucotoxicity by its antioxidant, antiapoptotic and insulin secretagogue actions. Food Chem 2013; 139(1-4): 362-70.
[http://dx.doi.org/10.1016/j.foodchem.2013.01.026] [PMID: 23561118]
[33]
Miladpour B, Rasti M, Owji AA, et al. Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro. J Endocrinol Invest 2017; 40(5): 513-21.
[http://dx.doi.org/10.1007/s40618-016-0592-8] [PMID: 28000178]

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