Polyhormonal aspect of the endocrine cells of the human fetal pancreas

Abstract

Histological studies were performed on 30 pancreases obtained from normal human fetuses aged between the 9th and 38th week. For immunocytochemistry, the avidin-biotin-peroxidase method was used to identify and colocalise insulin, glucagon, somatostatin, pancreatic polypeptide and proliferating cell nuclear antigen. In the 9th week, cells containing all investigated peptides were present. During the fetal period, two populations of endocrine cells have been distinguished, Langerhans islets and freely dispersed cells. The free cells were polyhormonal, containing insulin, glucagon, somatostatin and pancreatic polypeptide, and were localised in the walls of pancreatic ducts throughout the whole gland. During the development of the islets we have observed four stages: (1) the scattered polyhormonal cell stage (9th-10th week), (2) the immature polyhormonal islet stage (11th-15th week), (3) the insulin monohormonal core islet stage (16th-29th week), in which zonular and mantle islets are observed, and (4) the polymorphic islet stage (from the 30th week onwards), which is characterised by the presence of monohormonal cells expressing glucagon or somatostatin. Bigeminal and polar islets also appeared during this last stage. The islets consisted of an insulin core surrounded by a thick (in the part developing from the dorsal primordium) or thin rim (part of the pancreas concerned with the ventral primordium) of intermingled mono- or dihormonal glucagon-positive or somatostatin-positive cells. The most externally located polyhormonal cells exhibited a reaction for glucagon, somatostatin and pancreatic polypeptide. Apart from the above-mentioned types of islets, all arrangements observed in earlier stages were present. Proliferating cell nuclear antigen-positive cells (single in the large islets and more numerous in the smaller ones) were predominantly observed in the outermost layer. Taken together our data indicate that, during the human prenatal development of the islet, endocrine cells are able to synthesise several different hormones. Maturation of these cells involved or depended on a change from a polyhormonal to a monohormonal state and is concerned with decreasing proliferative capacity. This supports the concept of a common precursor stem cell for the hormone-producing cells of the fetal human pancreas.

Redifferentiation of Expanded Human Pancreatic β-Cell-derived Cells by Inhibition of the NOTCH Pathway

“…No co-expression of C-peptide and other hormones was detected, as seen in normal adult islets (35), in contrast to recent works aimed at generating insulin-expressing cells from ES cells, which show co-expression of islet hormones in the differentiated cells (36,37). Cells co-expressing several islet hormones are considered immature and found primarily among islet progenitor cells in the developing pancreas (38,39). Hence, the mutually exclusive expression pattern of islet hormones following the combined treatment indicates a relatively advanced differentiation of the stained cells.…”

Pancreatic β cell identity requires continual repression of non–β cell programs

“…Interestingly, during the early stages of human pancreas formation, the endocrine cells are initially polyhormonal and only gradually resolve into monohormonal cell identities (39). Intriguingly, unlike in mouse pancreatic development, where NKX2.2 is expressed early and there are only minor populations of polyhormonal cells, in humans NKX2.2 is not detected until late in pancreas formation, during the stage when monohormonal cells are acquired (40).…”

Ultrastructural and immunohistochemical analysis of the 8-20 week human fetal pancreas

“…Transmission electron microscopy analysis of human fetal pancreatic exocrine tissue has shown increases in rough endoplasmic reticulum and zymogen granules from 12 to 19 weeks fetal age. 11 Similar investigations of the human fetal endocrine compartment at 12-20 weeks fetal age have identified, by immunohistochemistry, numerous epithelial cells that not only contained multiple pancreatic endocrine hormones 12,13 but also individual granules containing multiple hormones, as analyzed by electron microscopy. 14,15 However, details of human pancreatic development at the ultrastructural level are limited.…”