Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The microRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

Version 1 : Received: 4 May 2021 / Approved: 6 May 2021 / Online: 6 May 2021 (15:01:45 CEST)

How to cite: Martens, G.A.; Stange, G.; Piemonti, L.; Anckaert, J.; Ling, Z.; Pipeleers, D.; Gorus, F.; Mestdagh, P.; De Smet, D.; Vandesompele, J.; Keymeulen, B.; Roels, S. The microRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts. Preprints 2021, 2021050095 (doi: 10.20944/preprints202105.0095.v1). Martens, G.A.; Stange, G.; Piemonti, L.; Anckaert, J.; Ling, Z.; Pipeleers, D.; Gorus, F.; Mestdagh, P.; De Smet, D.; Vandesompele, J.; Keymeulen, B.; Roels, S. The microRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts. Preprints 2021, 2021050095 (doi: 10.20944/preprints202105.0095.v1).

Abstract

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

Subject Areas

beta cell, type 1 diabetes, islet transplantation, biomarkers, microRNA

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