Successful Treatment of Diabetes in Nod Mice with Advanced Disease by Islet Isografts following Immunoregulation with Linomide (Quinoline-3-Carboxamide)

Abstract

We have recently documented that oral Linomide (quinoline-3-carboxamide) prevents autoimmune insulitis, islet destruction, and diabetes in NOD mice treated at an early stage (5 wk of age) of the disease. In this report, we show that treatment of female NOD mice with advanced disease (age 23-24 wk) by syngeneic islet transplantation and oral Linomide administration results in prevention of graft insulitis and diabetes in the Linomide group up to 40 wk (diabetes at 40 wk: isograft recipients with Linomide n = 0 of 6; isograft recipients alone n = 5 of 6; p < 0.0001). The extent of protection from glucose intolerance by the combination of transplantation with Linomide was superior to that of Linomide alone [blood glucose (mean +/- SD) 60 min post-i.p. injection of 1 g/kg body weight glucose: Linomide plus isograft 6.7 +/- 1 mmol/L; Linomide alone 18.7 +/- 6.3 mmol/L; p < 0.0001]. Thus, Linomide should be considered a potential immunoregulatory modality in patients undergoing pancreatic islet or whole organ transplantation.

Prevention of Diabetes in the NOD Mouse by Intra‐muscular Injection of Recombinant Adeno‐associated Virus Containing the Preproinsulin II Gene

“…I11 Furthermore, experiments in pregnant NOD mice also inhibited progression of DM, as it is well known that pregnancy is an immune-privileged state. I121 Other exogenously administered agents such as Linomide [13] and certain specific peptides [14] were also effective in preventing DM in NOD mice. Finally, introduction of gene mutations and MHC Class II genes also resulted in the prevention of DM in the NOD mice.…”