Oligonucleotide IMT504 Markedly Improves Metabolic Syndrome and Type 2 Diabetes in High-Fat Diet Fed Mice

DOMÉ L; RIAÑO JM; BONAVENTURA MM; FERNANDEZ M; MONTANER AD; LUX-LANTOS AR; BIANCHI MS

Chicago, IL

Congreso; ENDO 2023 Anual Meeting; 2023

The Endocrine Society

We have shown that the immunomodulatory oligonucleotide IMT504 (IMT) improves glucose homeostasis in several animal models of type 1 diabetes by regulating immunomodulatory factors and by improving beta-cell function. Here we evaluated the effects of IMT in a murine model of metabolic syndrome and type 2 diabetes induced by high-fat diet (HFD).Five weeks-old C57BL/6LP male mice were fed either standard diet (SD) or HFD (ResearchDiet, D12492) for 12 weeks. HFD mice showed higher non-fasting glycemia (NF-Gly: p˂0.01), and body weight (BW: p˂0.01). Thereafter, mice received one daily dose of IMT504 for 12 consecutive days [IMT(mg/kg/day), subcutaneous: 20, 6 or 2, only HFD mice) or saline (SD and HFD). Intraperitoneal glucose tolerance test (ipGTT, day 10), insulin secretion test (IST, day 10) and insulin tolerance test (ITT, day 11) were performed. On day 12, food intake (days 1-12), BW, and non-fasting Gly, were recorded; after 3 hours fasting, Gly were recorded, mice were sacrificed, and blood samples collected. Serum insulin levels were analyzed by ELISA.Food (F) and calories (C) consumed decreased with IMT treatment [F(g): ANOVA, p