Incretin Hormones and Beta-cell mass expansion: what we know and what is missing?

Pancreatic beta-cell mass expands through beta-cell proliferation and neogenesis while it decreases mainly via apoptosis. The loss of balance between beta-cell death and regeneration leads to a reduction of beta-cell functional mass, thus contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). The pathogenetic mechanisms causing T2DM are complex, and also include a significant reduction of the incretin effect. A better understanding of the role of incretin hormones in glucose homeostasis has led to the development of incretin-based therapies. Recently, incretin hormones have been shown to stimulate the beta-cell growth and differentiation from pancreas-derived stem/progenitor cells, as well as to exert cytoprotective, antiapoptotic effects on beta-cells. However, the role and the molecular mechanisms by which GLP-1 and its agonists regulate beta-cell mass have not been fully investigated. This review focuses the current findings and the missing understanding of the effects of incretin hormones on beta-cell mass expansion