Quercetin Ameliorates Chronic Type 2 Diabetes Induced by Long-Term High-Fat, High-Sucrose Diet via Modifying Expression of Genes Involved in Energy Homeostasis and Inflammation
Type 2 diabetes (T2D) is a metabolic health disorder that induces aberrant gene expression thought to maintain the disease persistent in absence of the initial triggers. The current T2D therapeutics pose adverse side effects, some of which are hypoglycemia and weight gain-exacerbated insulin resistance. We studied whether regulation of adiponectin (ADIPOQ), glucose transporter -2 (GLUT-2) and C-reactive protein (CRP) genes by quercetin would completely cure T2D induced by longterm consumption of high-fat, high-sucrose diet (HFHSD) in male Wistar rats. Thus, sixty male Wistar rats were randomized into three experimental groups (n=20): normal control (C) fed chow diet,diabetic control (D) fed the HFHSD and diabetic quercetin-treated(Q) fed the HFHSD and gavaged with quercetin at 80 mg.kg-1bw.day-1 starting on Day 0 through Day 120. On Days 0 and 120, rats were euthanized and blood samples were used to study the ensuinghyperglycemia, hyperinsulinemia, insulin resistance and plasma CRP concentration. The effect of quercetin on T2D-associated injury of islet of Langerhans and the relative splenic weight (RSPW%) was determined.Gene expression of ADIPOQ in epididymal fat and GLUT-2 and CRP in liver was assessed using RT-PCR. Quercetin attenuated the hyperglycemia, hyperinsulinemia, insulin resistance score and plasma CRP concentration on Day 120 in the Q rats. The number of islets of Langerhans was enhanced on Day 120 and the RSPW (%). decreased by quercetin on Day 120 in the Q rats. Quercetin also upregulated ADIPOQ and GLUT-2 genes and downregulated CRP gene in the Q rats on Day 120. In conclusion, quercetin ameliorated T2D induced by long-term HFHSD via regulating genes involved in energy homeostasis and inflammation leading to attenuation of the hyperglycemia and insulin resistance, the hallmark of T2D pathogenesis. Unlike currently in use anti-T2D therapy, adverse side effects were not triggered by quercetin.
