Similar developmental patterns of ghrelin and glucagon immunoreactivity in the human pancreas
Sanja Vignjevic, Vera Todorovic, Mileva Micic, Neda Drndarevic, Mirela Budec, Olivera Mitrovic, Dragoslava Djikic & Slavisa Djuricic
Ghrelin is stored alongside glucagon in developing islet, although in a discrete cellular compartment, the pancreatic ε-cell. However, recent observations have shown a subpopulation of ghrelin/glucagon-double-positive cells in developing pancreas. The aim of the present study was to examine the developmental patterns of ghrelin- and glucagon-immunoreactive (ir) cells expression and possible co-localization of these hormones during human pancreas development. For this purpose, paraffin-embedded pancreatic tissue sections from human embryos (2) and fetuses (24) were assessed by immunohistochemistry using antisera raised against ghrelin and glucagon. The collection and use of human embryonic and fetal material was carried out following ethical approval from the Local Ethics Committee.
Neither glucagon- nor ghrelin-ir cells were detected in the pancreas of 8-week-old embryos. A few ghrelin-positive cells were already observed at gestational age of 11 weeks, and by week 15, both glucagon and ghrelin-ir cells were found either within small cell clusters or as isolated cells adjacent to duct cells. From week 17 onwards, both cell types were observed at the periphery of the forming islet. The number of ghrelin- and glucagon-ir cells progressively increased during the second trimester of gestation, and slightly decreased during the third trimester. The highest percentage of ghrelin- and glucagon-positive cells was observed in the pancreas of second-trimester fetuses, where the cell density had reached 2.22% and 4.38%, respectively. Cells co-expressing ghrelin and glucagon were detected during both early and late fetal period, but they represent merely a small fraction of the total ghrelin- and glucagon-ir cells.
In conclusion, the similarities in developemental patterns of ghrelin- and glucagon-ir cells together with the presence of double-positive cells suggest the involvement of several common transcription factors that regulate cell-fate determination and differentiation of these cell populations.