Islet Neogenesis-Associated Protein (INGAP)-Positive Cell Mass, B-Cell Mass and Insulin Secretion: Their Relationship During the Fetal and Neonatal Periods.

MADRID VG; BORELLI MI; MAIZTEGUI B; FLORES LE; GAGLIARDINO JJ; DEL ZOTTO H

PANCREAS.

LIPPINCOTT WILLIAMS & WILKINS

Lugar: Philadelphia; Año: 2013 vol. 42 p. 422 - 428

0885-3177

Objective: To study the chronological appearance of pancreatic Islet Neogenesis-Associated Protein (INGAP)-positive cells and its correlation with the increase in β-cell mass and function in fetal and neonatal rats. Methods: Normal Wistar rat embryos (E) at gestational days 15, 17 and 19 (E15, E17, E19) and 7-day-old postnatal rats (P7) were sacrificed to determine body and pancreas weight, blood glucose, glucose and arginine-induced insulin secretion in vitro, realtime PCR of Pdx1 and Ngn3, and quantitative immunomorphometric analysis of β-cell replication and apoptosis rate, cytokeratin and INGAP cell mass, and Pdx-1- and Ngn-3-positive cells. Results: Body and pancreas weight increased with age (P7>E19>E17>E15; P < 0.05). Neonates had higher blood glucose concentrations than embryos (P < 0.05). We recorded a simultaneous and significant age-dependent trend of increase in the number of β- and Pdx-1-positive cells, β- and cytokeratin-positive cell mass and β-cell capacity to release insulin in response to glucose and arginine, and decreased β-cell apoptotic rate. These changes closely paralleled the increase in INGAP-positive-cell mass. Conclusions: These findings suggest that INGAP exerts a positive modulatory effect upon β-cell mass and its secretory function in fetal and neonatal rats, thus becoming a new component in the multifactorial regulation of such processes.