Expression of the protein tyrosine phosphatase-like protein IA-2 during pancreatic islet development

A tyrosine phosphatase-like protein, IA-2, is a major autoantigen in Type 1 diabetes but its role in islet function is unclear. Tyrosine phosphorylati on mediates regulation of cellular processes such as exocytosis, cell growt h, and cell differentiation. To investigate the potential involvement of IA -2 in islet differentiation and insulin secretion, we analyzed by immunohis tochemistry expression of IA-2 during islet development in fetal rats and d uring the maturation of insulin secretory responses after birth. In the fet us, IA-2 immunoreactivity was detected in primitive islets positive for ins ulin and glucagon at 12 days' gestation. Subsequently, IA-2 was only weakly detectable in the fetal pancreas. In neonatal rat, a progressive increase in IA-2 immunoreactivity was observed in islets from very low levels at 1 d ay of age to moderate labeling at 10 days. In the adult, relatively high le vels of IA-2 were detected in islets, with heterogeneous expression in indi vidual cells within each islet. IA-2 marks a population of endocrine cells that transiently appear early in pancreatic ontogeny. Islet IA-2 expression reappears after birth concomitant with the development of mature insulin s ecretory responses, consistent with a role for this protein in regulated ho rmone secretion.