Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.
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.
Kobori
Msauko
M
National Food Research Institute, National Agriculture and Food Research Organisation, Tsukuba, Ibaraki, Japan.
Masumoto
Saeko
S
Akimoto
Yukari
Y
Takahashi
Yumiko
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D020869:Gene Expression Profiling; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage*; D013311:Streptozocin; D025822:Ubiquitin C / Q000235:genetics
D001786:Blood Glucose; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007328:Insulin; D025822:Ubiquitin C; D013311:Streptozocin; D011794:Quercetin