Evidence for a Neogenic Niche at the Periphery of Pancreatic Islets

Abstract

We recently discovered a novel subset of beta cells that resemble immature beta cells during pancreas development. We named these ‘virgin’ beta cells as they do not stem from existing mature beta cells. Virgin beta cells are found exclusively at the islet periphery in areas that we therefore designated as the ‘neogenic niche’. As beta cells are our only source of insulin, their loss leads to diabetes. Islets also contain glucagon-producing alpha cells and somatostatin-producing delta cells, that are important for glucose homeostasis and form a mantle surrounding the beta cell core. This 3D architecture is important and determines access to blood flow and innervation. We propose that the distinctive islet architecture may also play an important, but hitherto unappreciated role in generation of new endocrine cells, including beta cells. We discuss several predictions to further test the contribution of the neogenic niche to beta cell regeneration.

Liraglutide and sitagliptin counter beta- to alpha-cell transdifferentiation in diabetes

“…Such observations clearly indicate that beta-cell dysregulation and insulin resistance are linked to detrimental alteration of pancreatic islet cell differentiation (Talchai et al 2012), regardless of disease pathogenesis. Given that T2DM patients have low levels of beta-cell apoptosis (Butler et al 2003), this would suggest that the beta-cell deficit in this disease is connected to beta-cell dedifferentiation or adverse betacell transdifferentiation (Huising et al 2018). Thus, betato alpha-cell transdifferentiation appears to be a normal phenomenon that is amplified in diabetes.…”

“…The deficit of betacell mass and function in diabetes is not well understood and has been linked to a loss of beta-cell identity, but related mechanism proves difficult to investigate (Accili et al 2010, Kitamura 2013). However, recent advances in cell lineage tracing technologies has shed light on the process of pancreatic beta-cells transitioning from their mature state to become dedifferentiated or transdifferentiated into other cell types (Collombat et al 2007(Collombat et al , 2009, Thorel et al 2010, Huising et al 2018. As such, beta-cell dedifferentiation is defined as a loss of beta-cell components, usually associated with an increase in the expression of progenitor markers, resulting in reduced insulin secretion (Weir et al 2013).…”

Mercury in Pancreatic Cells of People with and without Pancreatic Cancer

“…The carcinogenic potential of mercury would be enhanced if it were present in progenitor cells since these cells when dividing are likely to be susceptible to the genotoxic properties of mercury [10,11]. However, uncertainty remains as to the location of progenitor cells in the human pancreas, with the possibility that they exist in islets, acini, or ducts, or all three locations [25,[28][29][30][31][32]. Future studies combining elemental biomapping with immunostaining for progenitor and stem cell markers would be required to accurately determine the nature of these mercury-containing pancreatic cells.…”

Enzymatically stable analogue of the gut‐derived peptide xenin on beta‐cell transdifferentiation in high fat fed and insulin‐deficient Ins1Cre/+;Rosa26‐eYFP mice

“…This confirms that long‐acting xenin analogues, such as xenin‐25[Lys 13 PAL], retain direct beneficial pancreatic islet actions in diabetes. Given that xenin peptides influence both alpha‐ and beta‐cell mass, alongside a role for xenin in the maintenance of overall islet architecture, 12 this might indicate that xenin is impactful in the well renowned processes of islet endocrine cell differentiation 14‐17 . Indeed, lineage tracing studies reveal that pancreatic endocrine cell plasticity is highly relevant to diabetes, including dedifferentiation of mature insulin secreting beta‐cells towards non‐beta like endocrine cells in rodent and non‐rodent models, as well as humans 18‐23 …”