A SHORT-TERM TREATMENT WITH OLIGONUCLEOTIDE IMT504 INHIBITS INSULITIS AND LOWERS BLOOD GLUCOSE IN FEMALE NON-OBESE DIABETIC (NOD/Ltj) MICE

S BIANCHI; M MASSIMINO; C LIBERTUN; VA LUX-LANTOS; MS BIANCHI,

Orlando

Congreso; The Endocrine Society (USA). 99th Annual Meeting & Expo. 2017; 2017

We have shown that a long term-treatment with the immunomodulatory oligonucleotide IMT504 (20mg/kg/day) induced a marked recovery of glycemia (screened weekly), glucose clearence (by glucose tolerance test), insulin secretion (by area under the curve in insulin secretion test), and beta cell function (by HOMA beta cell index) on a spontaneous autoimmune diabetes model (in male and female NOD/Ltj mice).Considering previous results, we decided to analyze the minimun dose at which the IMT504 has an effect on glycemic control and insulitis with a short-term treatment. Female NOD/LtJ mice were screened weekly starting on week 10 by measuring glycemia (Gly) in fed conditions at noon. Animals were considered diabetic after two consecutive Gly levels ≥ 250 mg/dl. Thereafter, mice were treated with one daily dose of IMT504 for five days (IMT: 20mg/kg/day, 6mg/kg/day or 2mg/kg/day) or saline as diabetic control (DC). All mice were sacrificed the day following the last injection (day 6 after diabetes onset); after 3 hours fast, blood glucose was measured, animals were sacrificed by decapitation, blood samples were collected and pancreases were dissected for histological studies: hematoxylin-eosin staining for insulitis analysis, and insulin-glucagon staining for morphometric analysis.We observed that 12.5% (1/8) DC mice showed spontaneous reversion of the diabetic condition (normal blood glucose) whereas IMT treatment induced a marked improvement in blood glucose in 62.5% (5/8), 50% (4/8) and 75% (6/8) of mice with 2mg/kg/day, 6mg/kg/day, and 20mg/kg/day, respectively (X2: DC vs IMT20: p