PANCREATIC CELL

DIFFERENTIATION

What is the role of the pancreas in the human body?

The pancreas and liver have a common origin in embryogenesis. The mature pancreas consists of exocrine and endocrine components. The exocrine system produces digestive enzymes and sodium bicarbonate, while the endocrine portion produces hormones that control the level of glucose in the blood (20). Most stem cell research is focused on the possibility of regenerating endocrine cells. The endocrine portion of the pancreas contains islets of Langerhans, which consist of four different cell types that produce peptide hormones. The peptide hormones include insulin (from beta cells), glucagon (from alpha cells), somatostatin (from delta cells), and pancreatic polypeptide (from PP cells). In vivo, the pancreas develops from endoderm in contact with the notochord (14).
GENE EXPRESSION IN PANCREAS DEVELOPMENT

Differentiation of pancreas progenitors into the mature pancreas is a complicated process that is still not fully understood. Because most research focuses on the regeneration of endocrine rather than exocrine cells in vitro, the discussion will concentrate on islet cell differentiation. Early differentiation of pancreatic cells begins with the expression of Hnf6, Hlxb9, Hnf3 beta, and Pdx1, which appears to be the main player in pancreatic differentiation (20). The initial period of pancreatic differentiation ends with the expression of Pdx1, and the next round of development, which involves many transcription factors, leads to the differentiation of islet cells. Expression of Pax6 produces glucagon secreting alpha cells, while expression of Pax4 plays a role in the development of insulin producing beta cells and somastatin produces delta cells. The transcription factor Ngn3 is necessary for the production of all four endocrine cell types.

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FORMATION OF ISLETS

When endocrine cells are disassociated and cultured, they perform the remarkable task of reassembling into islet-like structures. Endocrine cells that are derived in vitro have the same capability of reassembling into such structures with three-dimensional structures like those of native islets, which are pictured below. The reassembled clusters of differentiated endocrine cells are functionally identical to islets in that they are capable of producing insulin, glucagons, somatostatin, and pancreatic polypeptide, the four peptide proteins secreted by the endocrine pancreas (14).
Understanding the differentiation of endocrine cells is essential for the development of possible therapies and treatments for endocrine dysfunctions, including diabetes.