Similar Developmental Patterns of Ghrelin- and Glucagon-Expressing Cells in the Human Pancreas

Abstract

The pancreas appears to be a major source of ghrelin during fetal development, but the ontogeny of ghrelin cells in the human pancreas and their developmental relationship with α- and β-cells remain largely unknown. In the present study, we examined the dynamics of ghrelin cell growth, colocalization of ghrelin with major pancreatic hormones and defined the similarities and differences among developmental patterns of ghrelin-, glucagon- and insulin-expressing cells in the human pancreas. To this end, paraffin-embedded pancreatic tissue sections from human embryos and fetuses were assessed by immunohistochemistry. Ghrelin-positive cells were first detected in the pancreas of 11-week-old fetuses. With advancing gestational age, both ghrelin- and glucagon-expressing cells were increasingly observed at the periphery of the developing islets, whereas insulin-containing cells were typically found in the islet core. Double immunohistochemistry showed that ghrelin-expressing cells were clearly separate from insulin-, somatostatin- and pancreatic polypeptide-containing cells. In contrast, cells coexpressing ghrelin and glucagon were sporadically detected during both the early and late fetal periods. Furthermore, morphometric analysis revealed a similar trend in the volume density of ghrelin- and glucagon-positive cells, and a contrasting pattern in β-cell density at specific time points during the development of the human pancreas. This study demonstrates that the developmental pattern of ghrelin cells, although clearly distinct, is quite similar to that of glucagon-expressing cells. The obtained findings indicate a close lineage relationship between these cell populations, a functional relationship between their secretory products and an auto/paracrine mode of ghrelin-glucagon interaction in pancreatic development.

Exogenous Ghrelin Increases Plasma Insulin Level in Diabetic Rats

“…Although reports have shown that ghrelin is produced by epsilon cells of the pancreas [57,59], we did not find ghrelin-positive granules in other cell types. Other studies have reported that ghrelin co-localized sporadically with glucagon in early and late fetal periods and eventually separate later in adult life [60]. Our study showed a close association with pancreatic beta cells, albeit in adult rats.…”

Brief demethylation step allows the conversion of adult human skin fibroblasts into insulin-secreting cells

“…The lack of differentiation into epsilon cells and ghrelin expression was a notable exception. A recent study on human pancreas development showed that epsilon cells have developmental features that are distinct from those of the other endocrine cells (43) and that at any stage of pancreatic development through to adult life, ghrelin peptide production is confined to a distinct cell type (18,44,45). These data suggest that epsilon cell ontogeny is somehow separated from the rest of the pancreatic endocrine cells and that the conversion process induced by the protocol used in our current study does not recapitulate this part of the pancreatic development.…”

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

“…Emerging studies have identified ghrelin-secreting cells (epsilon-cells) in the verges of pancreatic islets, suggesting that ghrelin affected beta cells through both the endocrine and paracrine pathways (Prado et al, 2004;Vignjević et al, 2012). Further study reported that ghrelin could stimulate insulin secretion (Granata et al, 2007), although inhibitory effects were also reported (Dezaki et al, 2004;Sun et al, 2006;Tong et al, 2010).…”