Annie Feray

Progressive Induction of Type 2 Diabetes: Effects of a Reality–Like Fructose Enriched Diet in Young Wistar Rats

Purpose The aim of this study was to characterize short and medium-lasting effects of fructose supplementation on young Wistar rats. The diet was similar to actual human consumption. Methods Three week old male rats were randomly divided into 2 groups: control (C; n = 16), fructose fed (FF; n = 16) with a fructose enriched drink for 6 or 12 weeks. Bodyweight, fasting glycemia and systolic blood pressure were monitored. Glucose tolerance was evaluated using an oral glucose tolerance test. Insulinemia was measured concomitantly and enable us to calculate insulin resistance markers (HOMA-IR, Insulin Sensitivity Index for glycemia: ISI-gly). Blood chemistry analyses were performed. Results After six weeks of fructose supplementation, rats were not overweight but presented increased fasting glycemia, reduced glucose tolerance, and lower insulin sensitivity compared to control group. Systolic blood pressure and heart weight were also increased without any change in renal function (theoretical creatinine clearance). After twelve weeks of fructose supplementation, FF rats had increased bodyweight and presented insulin resistance (higher HOMA-IR, lower ISI-gly). Rats also presented higher heart volume and lower ASAT/ALAT ratio (presumed liver lesion). Surprisingly, the Total Cholesterol/Triglycerides ratio was increased only after six weeks of fructose supplementation, predicting a higher LDL presence and thus a higher risk of developing cardiovascular disease. This risk was no longer present after twelve weeks of a fructose enriched diet. Conclusion On young Wistar rats, six weeks of fructose supplementation is sufficient to induce signs of metabolic syndrome. After twelve weeks of fructose enriched diet, rats are insulin resistant. This model enabled us to study longitudinally the early development of type 2 diabetes.

Effect of exercise training on oxidative stress and mitochondrial function in rat heart and gastrocnemius muscle

Abstract Objective This study aimed to explore the effect of endurance training on oxidative parameters and mitochondrial function in gastrocnemius and heart muscle. Methods Male Wistar rats were trained by running for 6 weeks. In vitro measurements of the rates of hydroxyl radical (•OH) production, oxygen consumption (in either the absence, basal rate (V0), or the presence, maximal rate (Vmax), of adenosine diphosphate), and adenosine triphosphate (ATP) production were made simultaneously in permeabilized fibers. The mitochondrial function was explored after exposure or non-exposure to an in vitro generator system of reactive oxygen species (ROS). Results Vmax was not affected by training, but V0 decreased. In conditions of maximal mitochondrial functioning, an increase in ATP rate and a decrease in •OH production occurred simultaneously. In vitro ROS exposure disturbed mitochondrial function, but training modified the vulnerability of Vmax and ATP rate to ROS in different ways. Discussion We hypothesize that the part of Vmax devoted to proton leakage was decreased in trained rats, consequently improving ATP synthesis. The data suggest that, after training, there is more efficient use of electrons in respiratory chain energy production, rather than a greater ROS scavenging capacity.

Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in Wistar Rats

Increased sugar consumption, especially fructose, is strongly related to the development of type 2 diabetes (T2D) and metabolic syndrome. The aim of this study was to evaluate long term effects of fructose supplementation on Wistar rats. Three-week-old male rats were randomly divided into 2 groups: control (C; n = 14) and fructose fed (FF; n = 18), with a fructose enriched drink (20–25% w/v fructose in water) for 21 weeks. Systolic blood pressure, fasting glycemia, and bodyweight were regularly measured. Glucose tolerance was evaluated three times using an oral glucose tolerance test. Insulin levels were measured concomitantly and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity Index for glycemia (ISI-gly)). Lipids profile was evaluated on plasma. This fructose supplementation resulted in the early induction of hypertension without renal failure (stable theoretical creatinine clearance) and in the progressive development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR, lower ISI-gly) without modification of glucose tolerance. FF rats presented dyslipidemia (higher plasma triglycerides) and early sign of liver malfunction (higher liver weight). Although abdominal fat weight was increased in FF rats, no significant overweight was found. In Wistar rats, 21 weeks of fructose supplementation induced a metabolic syndrome (hypertension, insulin resistance, and dyslipidemia) but not T2D.

0021 : Type II diabetes induced by a fructose enriched diet: benefits of exercise training

As hypertension or dyslipidemia, Type 2 diabetes (T2D) can occur in patients with metabolic syndrome and may result in endothelial dysfunction. Physical activity is part of the preventive treatment of endothelial dysfunction. The aims of this study were to develop a new animal model of induced T2D and to investigate the impact of exercise on T2D development (insulin resistance, antioxidant system, endothelial and vascular systems). Male Wistar rats were randomly divided into 4 groups: sedentary (Sed), sedentary fructose (SedFF), exercise (Ex) and exercise fructose (ExFF). SedFF and ExFF were supplemented with a fructose enriched drink (20% w/v) for 12 weeks. Exercise rats were trained on a treadmill at moderate intensity (60- 70% maximal aerobic speed) for 6 weeks (0 ° incline, 1h/day, 5 days/week). Glucose tolerance was evaluated using an oral glucose tolerance test; insulinemia was measured concomitantly. Activities of Glutathion Peroxidase (GPx), Catalase (CAT), Super Oxide dismutase (SOD) were measured in the heart and gastrocnemius. Endothelial function was studied on isolated aorta ring. Quantification of endothelial NO synthase (eNOS) and phosphorylated eNOS (eNOSP) were performed on myocarde. SedFF presented an insulin resistance (p In this model of Wistar rats with induced T2D, moderate exercise improved some markers of T2D but was not able to compensate all of its deleterious effects. The author hereby declares no conflict of interest

0108 : A new animal model of induced DT2 and its application in evaluating exercise benefits

Type 2 diabetes (DT2) is a major risk factor of atherosclerosis. As Hypertension or dyslipidemia, DT2 can occur in patients with metabolic syndrome and may result in endothelial dysfunction. Physical activity is a part of the preventive treatment of endothelial dysfunction. The aims of this study were to develop a new animal model of induced DT2 and to investigate the impact of exercise on the DT2 development. Male Wistar rats were supplemented with a fructose enriched drink (20% w/v) for 12 weeks. Randomly selected rats were either trained on a treadmill at moderate intensity (60-70% maximal aerobic speed) for 6 weeks (0° incline, 1h/day, 5 days/week) or kept sedentary. Rats were weighed and their drink and food consumption were measured weekly. Fasting glycaemia and systolic pressure were monitored. Glucose tolerance was evaluated using an oral glucose tolerance test; insulinemia was measured concomitantly. Endothelial function was studied on isolated aorta rings. After only 6 weeks of fructose supplementation rats had a higher energy intake (p