Dual origin, development, and fate of bovine pancreatic islets

Abstract

Endocrine cells are evident at an early stage in bovine pancreatic development when the pancreas still consists of primitive epithelial cords. At this stage, the endocrine cells are interspersed between the precursor cells destined to form the ductulo-acinar trees of later exocrine lobules. We here demonstrate that, in bovine fetuses of crown rump length ! 11 cm, the endocrine cells become increasingly segregated from the developing exocrine pancreas by assembly into two units that differ in histogenesis, architecture, and fate. Small numbers of 'perilobular giant islets' are distinguishable from larger numbers of 'intralobular small islets'. The two types of islets arise in parallel from the ends of the ductal tree. Aside from differences in number, location, and size, the giant and small islets differ in cellular composition (predominantly insulin-synthesising cells vs. mixtures of endocrine cells), morphology (epithelial trabeculae with gyriform and rosette-like appearance vs. compact circular arrangements of endocrine cells), and in their relationships to intrapancreatic ganglia and nerves. A further difference becomes apparent during the antenatal period; while the 'interlobular small islets' persist in the pancreata of calves and adult cattle, the perilobular giant islets are subject to regression, characterised by involution of the parenchyma, extensive haemorrhage, leukocyte infiltration (myeloid and T-cells) and progressive fibrotic replacement. In conclusion, epithelial precursor cells of the ductolo-acinar tree may give rise to populations of pancreatic islets with different histomorphology, cellular composition and fates. This should be taken into account when using these cells for the generation of pancreatic islets for transplantation therapy.

Influence of nutrient restriction and melatonin supplementation of pregnant ewes on maternal and fetal pancreatic digestive enzymes and insulin-containing clusters

“…However, when observing the size of insulin containing clusters, fetuses had a greater number of large islets compared with those of their respective dams amongst all treatments (Table 6). Similar results have also been observed when comparing calves to adult cattle (Merkwitz et al, 2012). In the examination of the pancreatic tissue of calves, islets of two differing sizes were discovered.…”

Effects of realimentation after nutrient restriction during mid‐ to late gestation on pancreatic digestive enzymes, serum insulin and glucose levels, and insulin‐containing cell cluster morphology

“…Merkwitz et al. () also examined the morphology of the foetal and cow pancreas and found islets of two differing sizes. The percentage of smaller islets (interlobular islets) was greater in foetal tissue.…”

Differentiation of pancreatic endocrine islets in buffalo fetus

“…1F). These islets of Langerhans has been named as secondary islets by Liu and Potter (1962) in human foetal pancreas, small islets by Bonner-weir and Like (1980) and intralobular islets by Merkwitz et al (2013) in bovine foetal pancreas. Many capillaries started to invade the endocrine cells of these islets.…”