TRANSCRIPTIONAL EFFECTS OF INGAP-PP PEPTIDE IN THE CONTROL OF THE PANCREATIC β-CELL MASS AND FUNCTION: A COMBINED EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS

CAROLINA L. ROMÁN; LUIS E. FLORES; AGUSTÍN ROMERO; MACARENA ALGAÑARAS; RODRÍGUEZ-SEGUÍ, SANTIAGO A.; ANA CAROLINA HEIDENREICH1; BÁRBARA MAIZTEGUI

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica (SAIC); 2022

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