Growth and development of the islets of Langerhans: implications for the treatment of diabetes mellitus.

In the past couple of years a number of major breakthroughs have been made in understanding the developmental biology of the islets of Langerhans. These include the involvement of the hedgehog signalling pathway in defining the region of the gut endoderm that will develop into the pancreas; the discovery that the transcription factor neurogenin3 and the Delta/Notch signalling pathway control endocrine cell differentiation through a lateral inhibition mechanism; and that alpha and beta cells are derived from an islet progenitor cell and follow independent lineage pathways rather than arising from a common mutihormonal progenitor cell as previously thought. This knowledge had been used in strategies to provide a replenishable supply of insulin-secreting cells for the treatment of diabetes mellitus. Thus, islet progenitor cells in adult pancreatic ducts or in isolated islets of Langerhans have been induced to grow in culture and their endocrine-like properties have been characterised. A proliferating beta-like cell line has been derived from tissue removed from a child with persistent hyperinsulinaemic hypoglycaemia of infancy and been engineered in culture to secrete insulin in response to glucose. And finally, embryonic stem cells have been shown to adopt islet-like characteristics under defined culture conditions.