info:eu-repo/semantics/article
Oligonucleotide IMT504 improves glucose metabolism and controls immune cell mediators in female diabetic NOD mice
Fecha
2021-04Registro en:
Bianchi, Stefania; Martínez Allo, Verónica Candela; Massimino Stepñicka, Milena; Lavignolle Heguy, María del Rosario; Borzone, Francisco Raúl; et al.; Oligonucleotide IMT504 improves glucose metabolism and controls immune cell mediators in female diabetic NOD mice; Mary Ann Liebert; Nucleic Acid Therapeutics; 31; 2; 4-2021; 155-171
2159-3337
CONICET Digital
CONICET
Autor
Bianchi, Stefania
Martínez Allo, Verónica Candela
Massimino Stepñicka, Milena
Lavignolle Heguy, María del Rosario
Borzone, Francisco Raúl
Gomez Bustillo, Sofia
Chasseing, Norma Alejandra
Libertun, Carlos
Montaner, Alejandro Daniel
Rabinovich, Gabriel Adrián
Toscano, Marta Alicia
Lux, Victoria Adela R.
Bianchi, Silvia María
Resumen
Type 1 diabetes occurs as a consequence of progressive autoimmune destruction of beta cells. A potential treatment for this disease should address the immune attack on beta cells and their preservation/regeneration. The objective of this study was to elucidate whether the immunomodulatory synthetic oligonucleotide IMT504 was able to ameliorate diabetes in NOD mice and to provide further understanding of its mechanism of action. We found that IMT504 restores glucose homeostasis in a diabetes mouse model similar to human type 1 diabetes, by regulating expression of immune modulatory factors and improving beta cell function. IMT504 treatment markedly improved fasting glycemia, insulinemia, and homeostatic model assessment of beta cell function (HOMA-Beta cell) index. Moreover, this treatment increased islet number and decreased apoptosis, insulitis, and CD45+ pancreas-infiltrating leukocytes. In a long-term treatment, we observed improvement of glucose metabolism up to 9 days after IMT504 cessation and increased survival after 15 days of the last IMT504 injection. We postulate that interleukin (IL)-12B (p40), possibly acting as a homodimer, and Galectin-3 (Gal-3) may function as mediators of this immunomodulatory action. Overall, these results validate the therapeutic activity of IMT504 as a promising drug for type 1 diabetes and suggest possible downstream mediators of its immunomodulatory effect.