EFFECTS OF A CONTINUOUS AND PROLONGED IMT504 TREATMENT IN DIABETIC FEMALE NOD MICE

BIANCHI S; LAVIGNOLLE HEGUY MR; MONTANER A; C LIBERTUN C; LUX-LANTOS V; BIANCHI MS

Ciudad de Buenos Aires

Congreso; XX Jornadas anuales de la Sociedad Argentina de Biologia y la XVII Jornada de la Sociedad Uruguaya de Biociencias; 2018

We have shown that the immunomodulatory oligonucleotide IMT504 (IMT) promotes a marked recovery of a toxic diabetes in rats that correlates with early expression of progenitor cell markers but without altering immune parameters. IMT also improves an immunodependent diabetes in mice, diminishing glycemia and reducing leukocyte islet infiltration. Besides, a short-term IMT treatment induces an early recovery on glucose homeostasis and insulitis on a model of type I diabetes, NOD mice. Here, we evaluated the effects of a continuous chronic IMT treatment in NOD diabetic mice, more similar to what could eventually be used in humans.Diabetic female NOD mice (non-fasted glycemia (Gly) levels between 250-350 mg/dl) were s.c. implanted with constant drug release pumps (Alzet osmotic pumps) with a capacity for 28 days, loaded with IMT (total dose released per day: 20 mg/kg BW) or saline (diabetic control: DC) (day1). Gly and body weight (BW) were determined once a week during the treatment. The weekly food intake was also determined. On day 21, glucose tolerance (ipGTT) and insulin secretion (IST) tests were performed. On day 28, fasted mice were sacrificed, blood samples and pancreases collected for hormonal determinations and histological studies respectively.We observed that 22% of NOD mice showed spontaneous reversion of the diabetic condition whereas IMT treatment ameliorated Gly in 78% of mice (X2: p