The current scarcity of high quality deceased pancreas donors prevents widespread application of islet transplantation for treatment of labile type 1 diabetes mellitus. Opportunities for the improvement of current techniques include optimization of islet isolation and purification, use of culture with pharmacologic insulinotropic agents, strategies to reduce graft rejection and inflammation, and the search for alternative insulin producing tissue. Here we report our findings on the efficacy of the long-acting human glucagon-like peptide 1 analogue, liraglutide, in a mouse model of marginal mass islet transplantation.

Liraglutide was administered (200 ug/kg sc twice daily) following a marginal mass syngeneic islet transplant in streptozotocin-induced diabetic BALB/c mice. Time-to-normoglycemia was significantly shorter in liraglutide treated animals (median 1 day vs. 7 days, p=0.0003), even in recipients receiving sirolimus (median 1 day vs. 72.5 days, p<0.0001). Liraglutide treated animals also demonstrated improved glucose tolerance as assessed by an intraperitoneal glucose tolerance test (IPGTT).

Liraglutide discontinuation at post-operative day 90 resulted in diminished glucose tolerance during IPGTT, while a late start liraglutide therapy 90-days post-transplant resulted in no improvement. These findings suggest that liraglutide therapy mediates early and late insulinotropic effects. In accord with this hypothesis, Insulin/TUNEL fluorescence microscopy showed reduced transplanted beta-cell apoptosis in liraglutide treated recipients 48 hours post-transplant. Additionally, liraglutide resulted in improved glucose dependent insulin secretion.

Overall, our data shows that liraglutide has a beneficial impact on the engraftment and function of syngeneic islet transplants in mice, when administered continuously starting on the day of transplant.