144. Early Improvement in Type I Diabetes in Mice By Oligodeoxynucleotide IMT504

BIANCHI MS; MONTANER A; MARTINEZ L; BIANCHI, STEFANÍA; CHASSEING NA; LIBERTUN C; LUX LANTOS V

Chicagp

Congreso; ICE/ENDO 2014; 2014

EARLY IMPROVEMENT IN TYPE I DIABETES IN MICE BY OLIGODEOXYNUCLEOTIDE IMT504 MS Bianchi1 , S Bianchi1, A Montaner2, L Martinez1, S Bianchi1, NA Chasseing1, C Libertun1, 3 and VA Lux-Lantos1 (1) Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (2) Fundación Pablo Cassará (ICT Milstein-CONICET), Buenos Aires, Argentina. (3) Facultad de Medicina, Universidad de Buenos Aires. Buenos Aires, Argentina. IMT504, the prototype of the PyNTTTTGT class of immunomodulatory oligonucleotides, accelerates tissue repair in models of bone injury and sciatic nerve crush. In addition, we have previously shown that IMT504 induces a marked recovery of single-dose streptozotocin (STZ)-induced toxic diabetes in male rats that correlates with early expression of progenitor cell markers (1), without altering immune parameters (2). IMT504 also improves the diabetic condition in an autoimmune diabetes model induced by multiple low doses of STZ in mice (MLDZ), evaluated 25 days after the end of IMT504 treatment. Here, we evaluated the early effects of IMT504 in MLDZ diabetic mice and its mechanism of action. Male Balb/C mice were ip-injected with STZ (40mg/kg) for 5 consecutive days or diluent as control (C). STZ mice with blood glucose ≥250 mg/dl and controls were daily sc-injected with IMT504 (IMT: 20mg/kg/dose) (STZ-IMT, C-IMT, respectively) or saline (STZ, C) and killed after two consecutive decreases in glycemia in STZ-IMT mice (2-5 doses of IMT). Blood samples and pancreases were collected for hormonal/cytokine determinations and histological studies. The prompt normalization observed in STZ-IMT blood glucose [glycaemia at sacrifice (mg/dl): C=137±14, C-IMT: 103±8, STZ: 352±41*, STZ-IMT: 145±9, * different from all: p