OLIGONUCLEOTIDE IMT504 IMPROVES INSULIN RESISTANCE AND VISCERAL ADIPOSE TISSUE STATE IN A METABOLIC SINDROME AND TYPE 2 DIABETES MURINE MODEL INDUCED BY HIGH-FAT DIET

DOMÉ L; RIAÑO JM; WHALE C; MALETTA C; MONTANER AD; LUX-LANTOS VAR; BIANCHI MS

Ciudad Autónoma de Buenos Aires

Jornada; XXIV JORNADAS ANUALES DE LA SOCIEDAD ARGENTINA DE BIOLOGIA; 2022

We have observed that the immunomodulatory oligonucleotide IMT504 induced a dose-dependent improve in glucose homeostasis, food intake and body weight in a metabolic syndrome (MS) and type 2 diabetes (D2T) murine model induced by high-fat diet. Here we evaluated the effects of IMT504 on insulin secretion, tissue insulin resistance, and visceral adipose tissue (VAT) in this model.C57BL/6LP male mice were fed either with 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 (p˂0.01). HFD mice received one daily dose of IMT504 for 12 consecutive days (ip? IMT: 20mg/kg/day, 6mg/kg/day or 2mg/kg/day) or saline. Insulin secretion tests (IST, day 10) were performed. On day 12; after 3 hours fasting, Gly were recorded, mice sacrificed and blood and VAT samples collected. Serum insulin levels (by ELISA), insulin resistance (by HOMA-IR) and key genes expression in VAT (by qPCR) were analyzed.Fasted insulinemia was higher in HFD mice and it significantly decreased with IMT treatment [ANOVA: p