CONICET | Buscador de Institutos y Recursos Humanos

of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats.Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation andoxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fedwith a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymaticactivity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks ofsuch a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers weresignificantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA alsoincreased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreaticinflammation markers also enhanced their gene expression in the last week of treatment. Whereasboth control and FRD rats remained normoglycemic throughout the entire period of treatment, bloodinsulin levels were significantly higher in FRD animals at the third week, thereby evidencing aninsulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated fromrats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM).Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together withintrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liveroxidative stress, liver and pancreas inflammation, pancreatic β-cell dysfunction, and peripheralinsulin-resistance registered at the third week. Knowledge of time-course adaptation mechanismsinvolved in our rat model could be helpful in developing appropriate strategies to prevent theprogression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diet