IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of Oligonucleotide IMT504 in Male and Female Non-Obese Diabetic (NOD) Mice, a Model of Spontaneous Development of Autoimmune Insulin Dependent Diabetes Mellitus
Autor/es:
BIANCHI S,; MONTANER AD; CHASSEING NA; MASSIMO M; PEREZ D; LIBERTUN C; LUX-LANTOS VA; BIANCHI MS
Lugar:
Boston
Reunión:
Congreso; 98th Annual Meeting & Expo of Endocrine Society; 2016
Institución organizadora:
Endocrine Society
Resumen:
Abstract aceptado diciembre 2015.We have shown that the immunomodulatory oligonucleotide 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) but without altering immune parameters (2).IMT504 also improves the diabetic condition in an immunodependent diabetes model induced by multiple low doses of STZ in mice (MLD-STZ), diminishing glycemia and reducing leukocyte islet infiltration. Here, we evaluated the effect of IMT504 on a spontaneous autoimmune diabetes model using NOD mice.Male and female NOD/LtJ mice were screened weekly starting on week 10 for diabetes onset by measuring glycemia (Gly) in tail blood with a glucometer in fed conditions at noon. Glycemia before diabetes onset was 114±3 in females and 121±3 in males. Animals were considered diabetics after two consecutive Gly levels ≥ 230 mg/dl. The mice were then treated with 4 series of 5 daily IMT504 doses (20mg/kg/day, sc) (IMT) or saline as diabetic control (DC) with 2 resting days between series. A total of 20 doses of IMT504 were administrated. Gly was measured in tail blood for a total of 38 days. At the end of the experiment, glucose tolerance tests (GTT) were performed (2g/kg BW glucose was injected ip, and glucose determined in tail blood samples). Five days later animals were sacrificed, blood samples and pancreases collected for hormonal determinations and histological studies respectively.We observed that 33% of male (3/9) and female (2/6) mice showed spontaneous reversion of the diabetic condition whereas IMT treatment induced a marked improvement in blood glucose in 70% of male (7/10) and 78% of female (7/9) mice respectively. In males, although Gly increased with time in both experimental groups, the enhancement was significantly lower in IMT-treated mice [repeated measures ANOVA; interaction ns, treatment and time effects, p