biostudies-literaturevan Tienhoven RThe Wanek Family Project for Type 1 DiabetesLeona M. and Harry B. Helmsley Charitable TrustStichting Diabetes Onderzoek NederlandIMI2-JUNIDDK NIH HHSJuvenile Diabetes Research FoundationZonMwDiabetes Fonds884-896https://www.ebi.ac.uk/biostudies/studies/S-EPMC10036285biostudies-literatureUnknown66(5)<h4>Aims/hypothesis</h4>Transcriptome analyses revealed insulin-gene-derived transcripts in non-beta endocrine islet cells. We studied alternative splicing of human INS mRNA in pancreatic islets.<h4>Methods</h4>Alternative splicing of insulin pre-mRNA was determined by PCR analysis performed on human islet RNA and single-cell RNA-seq analysis. Antisera were generated to detect insulin variants in human pancreatic tissue using immunohistochemistry, electron microscopy and single-cell western blot to confirm the expression of insulin variants. Cytotoxic T lymphocyte (CTL) activation was determined by MIP-1β release.<h4>Results</h4>We identified an alternatively spliced INS product. This variant encodes the complete insulin signal peptide and B chain and an alternative C-terminus that largelyDiabetologiaPresence of immunogenic alternatively spliced insulin gene product in human pancreatic delta cells.PMC10036285U24 DK098085G-2108-047935-SRA-2018-557-Q-R91111.006Kracht MJLThomaidou SCarlotti FRiojas JPRde Koning EJPRoep BOvan der Slik ARGiepmans BNGNelson MSZaldumbide Avan Tienhoven RHoeben RCWolters AHGfalsePresence of immunogenic alternatively spliced insulin gene product in human pancreatic delta cells.<h4>Aims/hypothesis</h4>Transcriptome analyses revealed insulin-gene-derived transcripts in non-beta endocrine islet cells. We studied alternative splicing of human INS mRNA in pancreatic islets.<h4>Methods</h4>Alternative splicing of insulin pre-mRNA was determined by PCR analysis performed on human islet RNA and single-cell RNA-seq analysis. Antisera were generated to detect insulin variants in human pancreatic tissue using immunohistochemistry, electron microscopy and single-cell western blot to confirm the expression of insulin variants. Cytotoxic T lymphocyte (CTL) activation was determined by MIP-1β release.<h4>Results</h4>We identified an alternatively spliced INS product. This variant encodes the complete insulin signal peptide and B chain and an alternative C-terminus that largely2023-01-01T00:00:00Z2023 May2026-07-14T19:09:03.973Z2025-02-19T00:49:41.469ZS-EPMC100362853688405710.1007/s00125-023-05882-y