Abstract
Pancreatic endocrine cells expressing the ghrelin gene and producing the ghrelin hormone were first identified in 2002. These cells, named ε cells, were recognized as the fifth type of endocrine cells. Differentiation of ε cells is induced by various transcription factors, including Nk2 homeobox 2, paired box proteins Pax-4 and Pax6, and the aristaless-related homeobox. Ghrelin is generally considered to be a “hunger hormone” that stimulates the appetite and is produced mainly by the stomach. Although the population of ε cells is small in adults, they play important roles in regulating other endocrine cells, especially β cells, by releasing ghrelin. However, the roles of ghrelin in β cells are complex. Ghrelin contributes to increased blood glucose levels by suppressing insulin release from β cells and is also involved in the growth and proliferation of β cells and the prevention of β cell apoptosis. Despite increasing evidence and clarification of the mechanisms of ε cells over the last 20 years, many questions remain to be answered. In this review, we present the current evidence for the participation of ε cells in differentiation and clarify their characteristics by focusing on the roles of ghrelin.
Highlights
The pancreas is a unique organ with both exocrine and endocrine functions
Up to the end of the previous century, pancreatic islets were thought to comprise four different cell types—α, β, δ, and pancreatic polypeptide (PP) cells—each producing different hormones. β cells occupy >60% of islet cells [2,3] and are involved in the production and release of insulin, which decreases blood glucose levels. α cells account for approximately 30% of islet cells [2] and produce the hormone glucagon, which acts to increase blood glucose levels
We summarize the development and characteristics of pancreatic ε cells and consider the roles of ghrelin released from the pancreas
Summary
The pancreas is a unique organ with both exocrine and endocrine functions. Its exocrine function is digestion, which it performs by secreting digestive enzymes from acinar cells into the duodenum via the pancreatic duct. They considered that Nkx2.2 is a key transcription factor involved in directing differentiation toward β or ε cells [41] They detected ghrelin-producing cells in the islets of wild-type mice during the prenatal period and showed that this population became very small in adults. In contrast to Nkx2.2 knockout, a small population of β cells was maintained in Pax knockout islets, while the expression of Pax, which is positively regulated by Nkx2.2, was not affected by Pax deletion They concluded that endocrine progenitors, stimulated by NGN-3, differentiate into β cells in the presence of Nkx2.2 or Pax and into ghrelin-producing ε cells in the absence of Nkx2.2 or Pax. This may explain why the population of pancreatic ε cells decreases in adults
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