Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs

ROMERO AGUSTIN; HEIDENREICH, ANA C.; ROMÁN CAROLINA LISI,; ALGAÑARAS MACARENA; GAGLIARDINO JUAN JOSE; MAIZTEGUI BARBARA; FLORES LUIS E.; RODRIGUEZ-SEGUÍ SANTIAGO

Mar del Plata

Congreso; LXVII ANNUAL MEETING OF SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2022

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Diabetes mellitus is characterized by chronic hyperglycemia and can lead to pancreatic β-cell loss. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas itself. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to improve β-cell mass and function. The aim of this work is to yield light into the mechanism of action underlying such effects. We performed RNA-seq analysis on rat pancreatic islets treated in vitro with INGAP-PP and integrated epigenetics data to further characterize transcriptomic effects of this treatment. We identify 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Among these we found genes that are selectively expressed in different cell types within pancreatic islets, proposing that INGAP-PP effects may potentially be reached by interaction of different cell populations. In-depth analysis reveals previously reported and novel signaling pathways potentially modulated by the peptide treatment, like Vegf, Pi3k, and Tgf-β pathway, as well as biological processes including angiogenesis and extracellular matrix organization. We report and validated by qRT-PCR (p