Islet neogenesis-associated protein (INGAP)-positive cell mass, β-cell mass, and insulin secretion: their relationship during the fetal and neonatal periods

Abstract

Objectives: 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 humanely killed to determine body and pancreas weight; blood glucose; glucose and arginine-induced insulin secretion; real-time polymerase chain reaction of Pdx1 and Ngn3; quantitative immunomorphometric analysis of β-cell replication and apoptosis rate, cytokeratin and INGAP cell mass, and Pdx-1– and Ngn3-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 on β-cell mass and its secretory function in fetal and neonatal rats, thus becoming a new component in the multifactorial regulation of such processes.