Oligonucleotide IMT504 Impacts mRNA Expression of Hormones and Progenitor Cell Markers in Langerhans Islets

BIANCHI MS; BIANCHI S; MONTANER AD; CHASSEING NA; MASSIMINO M; PEREZ D; LIBERTUN C; LUX-LANTOS VA

Boston

Congreso; 98th Annual Meeting & Expo of Endocrine Society; 2016

Endocrine Society

Abstract aceptado diciembre 2015.We have previously demonstrated that the immunomodulatory oligonucleotide IMT504 induces a marked recovery of toxic streptozotocin (STZ) induced diabetes in rats (1), without altering immune parameters (2). IMT504 also improves the diabetic condition in multiple low dose STZ-induced diabetes in mice, decreasing blood glucose and limiting leukocyte islet infiltration. The aim of the present work was to evaluate the in vivo effect of IMT504 on gene expression in fresh islets isolated from diabetic and control mice.Adult male BALB/C mice were injected for 5 consecutive days with STZ (40mg/kg, ip) or with its diluent (0.05M, pH=4.5 citrate buffer). Diabetic mice (non-fasted blood glucose levels ≥220 mg/dl) and controls were injected daily with IMT504 (20mg/kg, sc: STZ-IMT504, Control-IMT504) o saline (STZ-Saline, Control-Saline). Blood glucose was measured daily from tail blood with a glucometer. Mice were sacrificed after two consecutive blood glucose decreases in STZ-IMT504 mice. Mice from the other treatment groups were sacrificed at the same time. Islets were obtained by the collagenase method and RNA was obtained from islets by the Trizol method, as previously described (3). Gene expression was evaluated by qPCR.IMT504 rapidly normalized blood glucose in diabetic mice after 2 to 6 IMT504 injections: Glycemia (mg/dl): Control-Saline=125±4, Control-IMT504: 104±4, STZ-Saline: 355±21*, STZ-IMT504: 155±10, One ?way ANOVA, * different from all: p