Development and Life Cycle of a β‐Cell

Abstract

The understanding of the molecular biology of the pancreas β‐cell began 25 years ago with the cloning of the insulin cDNA, followed by the determination of the genomic organization and the identification of multiple cis ‐ and trans ‐acting elements in the 5′‐flanking region. The developmental biology of the pancreas started earlier but was put on hold until the molecular biological technology allowed approaching the questions raised some 30 years ago. A major breakthrough happened 8 years ago when disruption of the gene for an insulin gene transcription factor was found to ablate the development of the pancreas. This has greatly stimulated the search for new transcription factors and their regulation by growth and differentiation factors in order to understand the basal molecular mechanisms involved in the formation of the pancreas β‐cell and the perspectives for prevention, treatment, and cure of diabetes. The maintenance of an appropriate β‐cell mass depends on neogenesis from progenitor cells, proliferation of existing β‐cells, and β‐cell death. The balance between these processes is regulated by a complex interaction of metabolites, hormones, and growth factors. Under normal conditions there appears to be a close correspondence between insulin demand and the functional β‐cell mass. The function of the β‐cell is not only under acute regulation by nutrients following a meal but is also subject to regulation by chronic changes in the insulin demand as in pregnancy or obesity, which result in adjustment of the β‐cell number.

Regulation of beta cell replication

“…It is increasingly clear that pancreatic beta cells have the capacity to replicate themselves, albeit there is still much debate regarding the sources of the newly formed islets (Nielsen et al, 2001, Nielsen and Serup, 2004, Dor et al, 2004Bonner-Weir and Weir, 2005;Teta et al, 2007;Brennand et al, 2007Hanley et al, 2008;Xu et al, 2008). The mechanisms underlying the regulation of beta cell mass growth are complex, which includes cell cycle regulation that is central to cell replication.…”

Trefoil Factors Are Expressed in Human and Rat Endocrine Pancreas: Differential Regulation by Growth Hormone

“…P ANCREATIC MORPHOGENESIS IS a complex process involving multiple factors, in which intracellular signaling molecules, hormonal influences, growth factors, extracellular matrix components, and integrins participate in a coordinated manner (1)(2)(3)(4)(5)(6). It is increasingly evident that the establishment of cell-to-cell contact and the three-dimensional organization is an integral part for the end-stage differentiation of the pancreatic islets.…”