Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin‐induced disturbance of hepatic gene expression in mice

Abstract

Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury. We fed normal and STZ-induced diabetic mice with diets containing quercetin for 2 wk and compared the patterns of hepatic gene expression in these groups of mice using a DNA microarray. Diets containing 0.1 or 0.5% quercetin lowered the STZ-induced increase in blood glucose levels and improved plasma insulin levels. A cluster analysis of the hepatic gene expressions showed that 0.5% quercetin diet suppressed STZ-induced alteration of gene expression. Gene set enrichment analysis (GSEA) and quantitative RT-PCR analysis showed that the quercetin diets had greatest suppressive effect on the STZ-induced elevation of expression of cyclin-dependent kinase inhibitor p21(WAF1/Cip1) (Cdkn1a). Quercetin also suppressed STZ-induced expression of Cdkn1a in the pancreas. Dietary quercetin might improve liver and pancreas functions by enabling the recovery of cell proliferation through the inhibition of Cdkn1a expression. Unexpectedly, in healthy control mice the 0.5 and 1% quercetin diets reduced the expression of ubiquitin C (Ubc), which has heat-shock element (HSE) in the promoter region, in the liver.

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“…Briefl y, 100 l of serum was diluted with resistance ( 16 ), most recent studies have affi rmed that quercetin ameliorated insulin sensitivity in diet-induced ( 17,20,21 ), genetic (22)(23)(24), and chemical-promoted ( 7,22 ) diabetic model animals. Moreover, in HFD-fed mice, dietary quercetin could normalize the levels of proinfl ammatory TNF-␣ and interleukin-6 (IL-6) ( 20,23,25 ) and anti-infl ammatory adiponectin ( 17,20 ) in blood and/or WAT, suppress infl ammatory cells' infi ltration into liver and heart ( 6 ), and alter hepatic infl ammatory response gene expression ( 6, 19-21, 25, 26 ) and activity ( 26 ).…”

“…Supplemental Material can be found at: ( 16 ). Moreover, 0.5% or 1% quercetin diets, but not 0.1% quercetin diets, remarkably decreased the expression of ubiquitin C in healthy control mice ( 7 ). Therefore, to avoid the negative effects of excessive quercetin intake, we used 0.1% as the dose of dietary quercetin intervention in this study.…”

“…After 12 weeks of feeding, the serum concentration of quercetin was 9.19 ± 0.46 mol/l in mice fed quercetin-containing HFD. The concentration was at a comparative level with those in other related topic studies ( 7,17,20 ).…”

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“…Quercitrin (quercetin 3-O-a-L-rhamnoside) is converted to quercetin in the digestive tract. Among other effects, quercetin has also been shown to prevent oxidative injury and in parallel, it has a fat-lowering effect, improve diabetes-related impairments, and damp postprandial hyperglycemia in type 2 diabetes patients (Fiorani et al, 2010;Hussain et al, 2012;Kobori et al, 2009). The protective effect of dietary quercetin has been related with the inhibition of liver and pancreas CDKN1A gene expression (Kobori et al, 2009).…”

“…Among other effects, quercetin has also been shown to prevent oxidative injury and in parallel, it has a fat-lowering effect, improve diabetes-related impairments, and damp postprandial hyperglycemia in type 2 diabetes patients (Fiorani et al, 2010;Hussain et al, 2012;Kobori et al, 2009). The protective effect of dietary quercetin has been related with the inhibition of liver and pancreas CDKN1A gene expression (Kobori et al, 2009). Naringenin has been reported to correct triacylglycerides and cholesterol high levels, prevent the development of insulin resistance, and normalize glucose metabolism in mice fed with high-fat diet (Mulvihill et al, 2009).…”