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

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146821-e0146821
• Main Authors: Dupas, Julie, Goanvec, Christelle, Feray, Annie, Guernec, Anthony, Alain, Charlène, Guerrero, François, Mansourati, Jacques
• Format: Article
• Language: English
• Subjects: Age; Animals; Biology and Life Sciences; Blood; Blood glucose; Blood Glucose - metabolism; Blood pressure; Blood Pressure - drug effects; Body weight; Body Weight - drug effects; Cardiovascular disease; Cardiovascular diseases; Care and treatment; Cholesterol; Complications and side effects; Creatinine; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - chemically induced; Diet; Dietary supplements; Dietary Supplements - adverse effects; Enrichment; Fasting; Fructose; Fructose - adverse effects; Fructose - metabolism; Fructose - pharmacology; Glucose; Glucose tolerance; Glucose Tolerance Test; Glycemic Index - drug effects; Health risks; Heart; Human health and pathology; Hypertension; Insulin; Insulin - blood; Insulin resistance; Insulin Resistance - physiology; Laboratory testing; Life Sciences; Liver; Low density lipoprotein; Low density lipoproteins; Male; Medicine and Health Sciences; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - chemically induced; Obesity; Overweight; Oxidative stress; Physical Sciences; Random Allocation; Rats; Rats, Wistar; Renal function; Research and Analysis Methods; Rodents; Sensitivity; Sensitivity analysis; Tissues and Organs; Triglycerides; Type 2 diabetes; Weight Gain - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146821

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. 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. 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. 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.