EFFECTS OF OLIGONUCLEOTIDE IMT504 IN A METABOLIC SINDROME AND TYPE 2 DIABETES MODEL INDUCED BY HIGH-FAT DIET IN MICE

BONAVENTURA MM; DOMÉ L; MONTANER AD; LUX-LANTOS VAR; BIANCHI MS

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina de Inmunología (SAI), Sociedad Argentina de Fisiología (SAFIS) , French-Argentine Immunology Congress (FAIC)

We have shown that the immunomodulatory oligonucleotide IMT504 improves glucose homeostasis in animal models of type I diabetes by regulating expression of immune modulatory factors and by improving beta cell function. Here we evaluated the effects of IMT504 in a murine model of metabolic syndrome and type 2 diabetes induced by a high-fat diet.Male C57BL/6LP mice were fed either a standard diet (SD) or a high-fat diet (HFD: ResearchDiet, D12492) for 12 weeks. HFD animals showed higher non-fasting glycemia (Gly: p˂0.01), and body weight (BW: p˂0.01). Mice received one daily dose of IMT504 for 12 consecutive days (IMT: 20mg/kg/day, 6mg/kg/day or 2mg/kg/day) or saline. Glucose tolerance tests (GTT, day 10) and insulin tolerance tests (ITT, day 11) were performed. On day 12, food intake, BW, and non-fasted Gly were recorded; after 3 hours fasting, mice were sacrificed and blood samples collected. Gly did not vary with time in SD and HFD mice, while it significantly diminished with IMT treatment [Gly (mg/dl): repeated measures ANOVA: interaction, p