To β-e or Not to β-e Replicating after 30: Retrospective Dating of Human Pancreatic Islets

摘要

C creatic islet physiology is the origin of new insulin- producing B-cells that are generated in response to phys- iological demands postnatally. Harnessing this enigma would provide new means for the treatment of diabetes, a disease characterized by a gradual loss of B-cell mass (type 1 or type 2) and/or a decline in B-cell function combined with insulin resistance (type 2). Restraining destruction and stimulating regeneration of the functional mass would prevail over hyperglycemia and avoid secondary compli- cations such as retinopathy and nephropathy and, poten- tially, cardiovascular and cerebrovascular diseases (1). Four potential sources of regenerative B-cells, with their respective advocates in perpetual debate, have been pro- posed to represent the “Fountain of Youth”: 1) neogenesis of ductal epithelium cells (2, 3); 2) transdifferentiation of exocrine acinar cells (4); 3) differentiation of islet-derived precursor stem cells (5); and 4) B-cell replication. Despite strong evidence for the contribution of neogenesis and transdifferentiation in various models of animal pancre- atic injury, recent studies have called into question the role of these entities in B-cell mass expansion in the adult organ (6, 7). Strong skepticism also remains over the potential involvement of progenitor stem cells residing within the pancreas to give rise in vivo to functional B-cells (8). How- ever, B-cell replication, which was disregarded for many years, has lately gained popularity with lineage-tracing studies, demonstrating that preexisting mouse adult pan- creatic B-cells were the major source of new insulin-pro- ducing cells during adult life (9).