Abstract
Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water). Body weight, food, and beverage consumption were monitored and glucose, insulin, and lipid profiles were measured. Serum and liver triglyceride concentrations, as well as the expression of genes and proteins involved in lipid biosynthesis were assessed. The insulin-stimulated glucose uptake and isoproterenol-stimulated lipolysis were also measured in freshly isolated adipocytes. Even in the absence of obesity, this rat model already presented the main features of prediabetes, with fasting normoglycemia but reduced glucose tolerance, postprandial hyperglycemia, compensatory hyperinsulinemia, as well as decreased insulin sensitivity (resistance) and hypertriglyceridemia. In addition, impaired hepatic function, including altered gluconeogenic and lipogenic pathways, as well as increased expression of acetyl-coenzyme A carboxylase 1 and fatty acid synthase in the liver, were observed, suggesting that liver glucose and lipid dysmetabolism may play a major role at this stage of the disease.