薬物疫学と医薬品の安全性の進歩

概要

Quercetin Curtails Obesity and Dyslipidemia, but Not Insulin Resistance in Long-Term Type 2 Diabetic Male Wistar Rats Fed the High-Fat, High-Sucrose Diet

Almass A Abuzaid, Mohamed A Osman and Abdalla O Elkhawad

It is unclear whether the persistence of Type 2 Diabetes (T2D)-associated insulin resistance in Wistar rats is entirely dependent on obesity and dyslipidemia or other factors are involved. We wanted to reveal whether alleviation of obesity and dyslipidemia by quercetin would sufficiently cure the insulin resistance in diabetic Wistar rats. For this purpose, ninety, male Wistar rats were randomized into three experimental groups (n=30): Normal Control (NC) fed chow diet, Diabetic Control (DC) fed High-Fat, High- Sucrose Diet (HFHSD) and diabetic, Quercetin-Treated (QT) fed the HFHSD and gavaged with quercetin at 50 mg.kg-1 bw.day-1. On Days 0, 60 and 120, Body Mass Index (BMI) and Abdominal Circumference:Thoracic Circumference (AC:TC) ratio were measured on ten rats from each group. Rats were then euthanized and fasting blood samples were withdrawn and used to quantify plasma glucose, Triacyclglycerols (TAG), LDL-cholesterol, total cholesterol, C-Reactive Protein (CRP) and insulin concentrations. Insulin resistance score, Relative Pancreatic Weight (RPW, %) and number of islet of Langerhans were also determined. We show that quercetin normalized BMI, AC:TC ratio, RPW (%) and dyslipidemia, and enhanced the islets number of Langerhans in the QT rats on Day 120 relative to the NC rats. In the diabetic DC rats, AC:TC ratio correlated positively with hyperglycemia and negatively with RPW (%). Quercetin lowered, but failed to normalize hyperinsulinemia, insulin resistance score, hyperglycemia and CRP in the QT rats relative to the NC rats suggesting that other factors are involved in the insulin resistance pathogenesis in T2D Wistar rats. Our data also suggest that AC:TC ratio is a predictor of the obesity-induced T2D in Wistar rats.