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

ROMÁN, CAROLINA L.; FLORES, LUIS E.; GAGLIARDINO, JUAN J.; RODRÍGUEZ SEGUÍ, S.A.; ROMERO, AGUSTÍN; MAIZTEGUI, BÁRBARA

Buenos Aires

Encuentro; Xth Meeting of the Latin American Society for Developmental Biology; 2019

Latin American Society for Developmental Biology (LASDB)

Diabetes Mellitus (DM) is a disease characterizedby the lost or reduction of the pancreatic βcell mass and the consequent diminution of insulin production. Nowadays, one of the most attractive therapeutic treatments is tryingto leverage the innate regenerative potential of the pancreas. Apancreatic protein, INGAP (homologous to REG3γin mouse) increases the β cell mass andthe insulin secretion. The same effect is achieved with apentadecapeptide, INGAP-PP, containing an inner sequence of INGAP.Here we will present our ongoing work to characterize thetranscriptomic and epigenomic effects of INGAP-PP, as well as thepotential 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-seqassays on rat pancreatic islets treated invitro with INGAP-PP. Our preliminaryresults suggest that the INGAP-PP activates pathways associated withGABA signaling and interactions with cells of the immune system,among others. In this context, INGAP-PPcould reduce the immunoregulatory interactions between islet- andlymphoid-cells, reducing the activation of cytokine-mediated pathwaysand leading the tissue regeneration through an anti-inflammatoryenvironment. Interestingly, a re-analysis of public RNA-seqdatasets, profiled in purified pancreatic cell populations throughoutβ cell development, revealed that the expression of genes codingfor proteins of the REG3 family is strongly enhanced in12-day-postnatal β cells. This coincideswith the expansion and maturation period of these cells, and suggestsan important role of REG3 proteins during the neonatal period. Thus,the effects of the REG3/INGAP proteins might have more functions thaninitially expected, opening new avenues of research. Gainingfurther insights into the molecular mechanisms through which theINGAP-PP excerpts its effects is expected to help developing animproved treatment for diabetic patients.p { margin-bottom: 0.1in; direction: ltr; color: rgb(0, 0, 0); line-height: 115%; text-align: left; }p.western { font-family: "Calibri", serif; font-size: 11pt; }p.cjk { font-family: "Calibri"; font-size: 11pt; }p.ctl { font-size: 11pt; }a:link { color: rgb(0, 0, 255); }