Cellular differentiation in the embryonic rat pancreas, with special reference to the co-existence of substances immunoreactive to both insulin and glucagon antibodies in the same cells.

We used light and electron microscopy and immunohistochemistry to examine the pancreas primordium in 11- to-20-day-old rat embryos. Cells that were immunoreactive to glucagon-like antibodies (G-like cells) first appeared under light microscopy on day 11, and those immunoreactive to insulin-like antibodies (I-like cells) appeared on day 13. All the I-like cells also reacted to G-like substance antibody. From the 13th to the 17th day of gestation, the G-like cells proliferated rapidly while the I-like cells increased in number very slowly. All the I-like cells continued to react with G-like substance antibody as well. The I-like cells began increasing rapidly on the 18th day and soon occupied about half of the islet-constituting cells. They no longer reacted with G-like substance antibody. Using double-label immunostaining with protein A-colloidal gold, the pancreatic endocrine cells became visible in 15-day-old embryos as large polygonal cells containing numerous secretion granules 180-200 nm in diameter. Some of these cells reacted to both I-like and G-like substance antibodies. These findings show the co-existence of G-like and I-like substances in rat embryo pancreatic endocrine cells between the 13th and 17th days of gestation, after which the I-like cells proliferate rapidly, and undergo definitive differentiation from the G-like cells.