Pancreatic beta-cells: from generation to regeneration

Abstract

The pancreas is composed of two main compartments consisting of endocrine and exocrine tissues. The majority of the organ is exocrine and responsible for the synthesis of digestive enzymes and for their transport via an intricate ductal system into the duodenum. The endocrine tissue represents less than 2% of the organ and is organized into functional units called islets of Langerhans, comprising alpha-, beta-, delta-, epsilon- and PP-cells, producing the hormones glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide (PP), respectively. Insulin-producing beta-cells play a central role in the control of the glucose homeostasis. Accordingly, absolute or relative deficiency in beta-cells may ultimately lead to type 1 and/or type 2 diabetes, respectively. One major goal of diabetes research is therefore to understand the molecular mechanisms controlling the development of beta-cells during pancreas morphogenesis, but also those underlying the regeneration of adult injured pancreas, and assess their significance for future cell-based therapy. In this review, we will therefore present new insights into beta-cell development with focus on beta-cell regeneration.

Beta-cell development and regeneration

Schematics representing various roadmaps leading to the generation of functional insulin-producing cells. During embryonic development, beta-cells are generated from Ngn3⁺ progenitors. Moreover, beta-cells have the capacity to undergo self-replication to expand the beta-cell mass. This occurs during development, pregnancy, and following injury. Findings from several independent studies, using various pancreas injury models, are consistent with the idea that stem/progenitor cells do exist in the adult pancreas. Several sources of facultative stem/progenitor cells were suggested and are depicted: duct epithelium, acinar cells, centroacinar (CA)/terminal duct (TD), and intra-islet progenitors. Glucagon⁺, Pdx1⁺, and Ngn3⁺ were often found in the duct lining, suggesting that this may be a site where stem/progenitor cells at least transiently reside.