Continuous, prolonged treatment with the oligonucleotide IMT504 in diabetic NOD mice greatly improves all parameters of the diabetic condition.

BIANCHI, STEFANÍA; LIBERTUN CARLOS; LAVIGNOLLE HEGUY MR; LUX LANTOS V; MONTANER A; BIANCHI, M S

New Orleans

Congreso; ENDO 2019, 101st Annual Meeting of the Endocrine Society,; 2019

The Endocrine Society

Continuous, prolonged treatment with the oligonucleotide IMT504 in diabetic NOD mice greatly improves all parameters of the diabetic conditionStefania Bianchi1, María del Rosario Lavignolle Heguy1, Alejandro Montaner2, Carlos Libertun1,3, Victoria Adela Lux-Lantos1 and María Silvia Bianchi1.1IBYME-CONICET, Buenos Aires, Argentina.2ICT Milstein-CONICET, Buenos Aires, Argentina.3Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. We have shown that the immunomodulatory oligonucleotide IMT504 (IMT) induces a marked recovery of single-dose streptozotocin (STZ)-induced toxic diabetes in rats that correlates with early expression of progenitor cell markers but without altering immune parameters. IMT also improves the diabetic condition in an immunodependent diabetes model induced by multiple low doses of STZ 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 spontaneous 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 (two consecutive 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 in weeks 1 and 4. On day 21, the intraperitoneal glucose tolerance test (ipGTT) and insulin secretion test (IST) 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