Ontogenic development of peptide hormones in the mammalian fetal pancreas

Abstract

The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human, pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal beta-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell-types.

Decreased beta-cell proliferation impairs the adaptation to pregnancy in rats malnourished during perinatal life

“…This specific regional adaptation could also suggest that the islets from the head and the tail respond to different stimuli. Furthermore, the head part of the pancreas is composed of PP-rich islets with fewer glucagon cells, whereas the tail corresponds to a glucagonrich and PP-poor region (Orci 1982, Reddy & Elliott 1988. To what extent this regional islet cell repartition plays a role in the preferential adaptation of -cell mass and proliferation in the head of the pancreas remains to be determined.…”

Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep

“…Species differences in response to neonatal exendin-4 might reflect differences in timing of pancreas development (4,15,26,41,46,48,59) and hence, timing of the IUGR insult and exendin-4 intervention relative to pancreas development. Although the adult sheep is a ruminant, we do not consider that this explains the smaller effects of neonatal exendin-4 on adult glucose tolerance in this species.…”

“…Development of the pancreas in humans and sheep occurs mostly before birth, with ␤-cells appearing within the first quarter of gestation, islet development by midgestation, and substantial remodeling to a functional endocrine pancreas near term (26,41,46,59). In fetal sheep, in vivo glucose-stimulated insulin secretion, particularly early or first-phase insulin secretion, matures from midgestation and increases during the last quarter of gestation (4,15).…”

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction

“…This ovine model of IUGR also has the advantage, particularly for studies of insulin secretion responses to interventions, that the timing of pancreas development is more similar to humans than to rats. In sheep, as in the human, development of the pancreas is mostly prenatal (6,33,57,67,88,102,107,114), hence subject to effects of IUGR, whereas development of the rat pancreas commences later in pregnancy and continues after birth (81,101,107,119). In fetal sheep and humans, ␤-cells can be detected by ϳ25% of term, with islets and insulin secretory function evident by midgestation (6,33,57,67,102,107), whereas ␤-cells are not present in the fetal rat until ϳ60% of term (107).…”

“…In sheep, as in the human, development of the pancreas is mostly prenatal (6,33,57,67,88,102,107,114), hence subject to effects of IUGR, whereas development of the rat pancreas commences later in pregnancy and continues after birth (81,101,107,119). In fetal sheep and humans, ␤-cells can be detected by ϳ25% of term, with islets and insulin secretory function evident by midgestation (6,33,57,67,102,107), whereas ␤-cells are not present in the fetal rat until ϳ60% of term (107). The pancreas undergoes a wave of apoptosis and developmental remodeling to a glucose-responsive phenotype, which occurs before birth in sheep and humans (57,67,88,114) but during days 10 -17 after birth in rats (81,101,119).…”