title: Islet neogenesis-associated protein (INGAP)-positive cell mass, β-cell mass, and insulin secretion: their relationship during the fetal and neonatal periods.
abstract: 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 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.
authors.affiliation: CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP, CONICET LA PLATA; Centro Colaborador OPS/OMS), Facultad de Ciencias Médicas UNLP, La Plata, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Madrid
authors.forename: María I
authors.initials: MI
authors.lastname: Borelli
authors.forename: Bárbara
authors.initials: B
authors.lastname: Maiztegui
authors.forename: Luis E
authors.initials: LE
authors.lastname: Flores
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
authors.forename: Héctor Del
authors.initials: HD
authors.lastname: Zotto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001835:Body Weight; D002452:Cell Count; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009024:Morphogenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D000073718:Pancreatitis-Associated Proteins; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D007328:Insulin; D007633:Keratins; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D000073718:Pancreatitis-Associated Proteins; D015534:Trans-Activators; C498696:Neurog3 protein, rat; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; C084010:pancreatic and duodenal homeobox 1 protein