Differentiation and growth of pancreatic beta cells

Although beta-cell mass increases mainly during embryonic and foetal life, some increase can also occur during adult life in certain physiological and physiopathological conditions. This increase in beta-cell mass during these different periods can be explained by the differentiation of immature beta cells into insulin-producing cells and by the proliferation of preexisting beta cells. Some data are now available on the soluble factors involved in the control of beta-cell proliferation. For example, somatolactogenic hormones play an important role in beta-cell growth, at least during gestation. On the other hand, there are few data on beta cell differentiation, essentially because no simple experimental system exists to conduct such studies. Few markers of immature beta cells are available. It has been proposed that immature beta cells could express tyrosine hydroxylase, the first enzyme of the catecholamine biosynthetic pathway, but additional markers are needed to further characterize these immature cells. The signals involved in the differentiation of these immature cells into insulin-producing ones are not yet known. Soluble factors produced by the embryonic pancreatic mesenchyme could play an important role in islet-cell differentiation. Finally, because beta and neuronal cells share a large number of similarities, the same events could be implicated in the differentiation of these two cell types. Thus, neurotrophic factors could be involved in the development of beta cells. The fact that foetal beta and pancreatic ductular cells express nerve growth factor receptors supports this hypothesis.