{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:30:44Z","timestamp":1759336244752,"version":"3.41.2"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T00:00:00Z","timestamp":1695945600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetes mellitus is characterized by chronic hyperglycemia with loss of \u03b2-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce \u03b2-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP <jats:italic>in vitro<\/jats:italic> treatment of adult rat pancreatic islets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and findings<\/jats:title><jats:p>Rat pancreatic islets were cultured <jats:italic>in vitro<\/jats:italic> in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a <jats:italic>de novo<\/jats:italic> rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1\u03b2, IL1\u03b2+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1\u03b2 and vitamin D in \u03b2-cells. These include <jats:italic>Ri-lnc1<\/jats:italic>, which is enriched in mature \u03b2-cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on \u03b2-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic \u03b2-cells and downregulated by IL1\u03b2 treatment of INS-1 cells. Our results suggest a relevant function for <jats:italic>Ri-lnc1<\/jats:italic> in \u03b2-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1226615","type":"journal-article","created":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T21:43:27Z","timestamp":1696110207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs"],"prefix":"10.3389","volume":"14","author":[{"given":"Agust\u00edn","family":"Romero","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana C.","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina 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