Insulin-secreting cell regeneration: a dream or reality?

Abstract

189 ISSN 1758-1907 10.2217/DMT.13.12 © 2013 Future Medicine Ltd Diabetes Manage. (2013) 3(3), 189–191 Autoimmune destruction of insulinproducing b-cells leads to Type 1 diabetes (T1D). The global challenge to find a cure for T1D centers on transplanting or regenerating insulin-producing cells, while at the same time preventing disease recurrence. This quest for cure dominates prevention in the public’s mind, although in reality there can be no cure of an autoimmune disease without prevention. The impetus comes from the demands of daily insulin injections to treat T1D and the inability of this approach to attain physiologic control of blood glucose, in many cases leading to longer-term complications secondary to hyperglycemia. Although transplantation of the pancreas or purif ied islets allows near-normal maintenance of blood glucose, it comes at a high technical and financial cost and is severely limited by the shortage of organ donors. In addition, long-term insulinindependence appears to be the exception rather than the rule [1]. Alternative sources of b-cells, primarily embryonic or adult stem/progenitor cells, have, therefore, been pursued [2–5]. Turning the dream of regenerating b-cells into a reality requires an understanding of normal b-cell ontogeny and how to mimic and evaluate it. The b-cell regeneration progress has to match the known molecular identity of a developing pancreas. Over the last 30 years, pancreatic endocrine cell lineages have been mapped through the role of specialized growth factors and sequential activation/inhibition of signaling pathways. Thus, early specification of dorsal and ventral pancreatic buds from foregut endoderm requires Hedgehog and FGF signaling [6]. Growth and branching morphogenesis involve FGF, Notch, Wnt, TGF-b and EGF pathways [7]. These pathways are activated by interactions with surrounding tissues, causing expression of specialized transcription factors. Sets of transcription factors form transcriptome signatures responsible for tissue transformation. Although incomplete, these groups are used to identify whether cultivated cells reached late-def initive endoderm, pancreatic progenitor or immature b-cell stages of development. In addition, the b-cell regeneration progress has to match known b-cell function. Cellular response to incretins, such as glucose and exenatide, is a valuable feature. It displays insulin production, reveals presence of secretory networks and detects dose-dependent insulin