INGAP and the control of pancreatic B cell mass and function: transcriptional effects

ROMERO AGUSTÍN; RODRÍGUEZ SEGUÍ, SANTIAGO A; ROMÁN, CAROLINA LISI; MAIZTEGUI, BÁRBARA; FLORES, LUIS EMILIO; GAGLIARDINO, JUAN JOSÉ

Buenos Aires

Congreso; Latin Amarica Society for Developmental Biology LASDB Meeting 2019; 2019

Latin Amarica Society for Developmental Biology LASDB

Diabetes Mellitus is a disease characterized by the loss or reduction of thepancreatic B cell mass, the consequent diminution of insulin production and theincapability of maintain glycaemia in a normal range. Nowadays, one of the mostpromising therapeutic treatments is trying to leverage the innate regenerativepotential of the endocrine pancreas. A pancreatic protein, INGAP (homologous toREG3􀈖 in mouse) increases the B cells mass, vascular neogenesis and insulinsecretion. The same effect is achieved with a pentadecapeptide, INGAP-PP,containing an inner sequence of INGAP. Here we will present our ongoing work tocharacterize the transcriptomic and epigenomic effects of INGAP-PP, as well asthe potential effects of INGAP (and more widely REG3 proteins) in otherregenerative settings of the pancreas. To profile the transcriptomic response of ratpancreatic islets to the INGAP-PP treatment, we performed RNA-seq assays onINGAP-PP-treated-islets. Our preliminary results suggest that INGAP-PP activatespathways associated with GABA signaling and interacts with cells of the immunesystem, among others. In this context, INGAP-PP could reduce theimmunoregulatory interactions between islet and lymphoid-cells, reducing theactivation of cytokine-mediated pathways and leading the tissue regenerationthrough an anti-inflammatory environment.