Background.Circulating level of the pancreatic islet enriched miR-375  was recently described as a biomarker of  beta cell death¹. We tested if circulating levels of miR-375 reflect beta cell destruction in patients with type 1 diabetes  who received human pancreatic islets.

Methods/Materials.A total of 22 human islet infusion were studied under different immunosuppression regimen: alphaCD25/Rapa/FK506 (n=6), ATG/MMF/FK506 (n=13) and none (auto trasplantation; n=3). MiR-375 circulating levels were evaluated by quantitative PCR (TaqMan Assay and/or droplet digital PCR).

Results.Human pancreatic islet expressed high level of miR-375. After transplantation serum miR-375 increased up to 200-fold during the first 12 hours, and then dropped to moderately elevated levels after 24 hours. This change was present both in allogenic and autologous islet transplantation. Circulating miR-375 levels were again increased at 96 hours post islet-infusion. This second peak  was  preceded by the rise of C-reactive protein  and cross-linked fibrin degradation products, and it was followed by the rise of cell damage markers (AST, ALT and LDH). We compared miR-375 levels in patients with and without CXCR1/2 inhibitor therapy, a treatment that preserves <beta> cell mass by dampening inflammatory damage (Citro, A. et al J. Clin. Invest. 2012;122:3647). All patients showed similarly increased circulating miR-375 levels during the 24 hr period that followed the infusion. However, the elevations of miR-375 levels that were observed at 48 and 96 hours post-islet infusion in control patients were not observed  in patients treated with CXCR1/2inihibitors (p=0.048 and 0.024, respectively). Concordantly, CXCR1/2 inhibitor therapy preserved increased beta cell function during the time.