EFFECT OF OLIGONUCLEOTIDE IMT504 IN MALE AND FEMALE NON-OBESE DIABETIC (NOD) MICE, A MODEL OF SPONTANEOUS DEVELOPMENT OF AUTOIMMUNE INSULIN DEPENDENT DIABETES MELLITUS.

BIANCHI S; A MONTANER; CHASSEING A; MASSIMINO M; PEREZ DA; LIBERTUN C; LUX LANTOS V; BIANCHI MS

Mar del Plata

Congreso; Reunión Conjunta Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina Inmunología (SAI) y Sociedad Argentina de Farmacología Experimental (SAFE).; 2016

Sociedad Argentina de Investigación Clínica (SAIC), Sociedad Argentina Inmunología (SAI) y Sociedad Argentina de Farmacología Experimental (SAFE).

We have shown that the immunomodulatory oligonucleotide IMT504 induces marked recovery of single-dose streptozotocin (STZ)-induced toxic diabetes in rats, correlating with early expression of progenitor cell markers (1), without altering immune parameters (2). IMT504 also improves diabetes in an immunodependent model induced by multiple low doses of STZ in mice, diminishing glycemia (Gly) and reducing leukocyte islet infiltration (3). Here, we evaluated the effect of IMT504 on spontaneous autoimmune diabetes using NOD mice.Mice were considered diabetic after two consecutive non-fasted Gly levels ≥ 230 mg/dl. Diabetics were treated with 4 series of 5 IMT504 doses (20mg/kg/day, sc) (IMT) or saline as control (DC) with 2 resting days between series. After one week, glucose tolerance tests (GTT) were performed (2g/kg BW glucose ip). Five days later mice were sacrificed, blood samples and pancreases collected for hormonal determinations and histological studies.Spontaneous reversion of the diabetic condition was observed in 33% of male (M) and female (F) mice whereas 70% of M and 78% of F improved their Gly after IMT treatment. In M, Gly increase was lower in IMT-treated mice vs. DC [repeated measures ANOVA; interaction ns, treatment and time effects, p