Sherlock Holmes and the Mysterious Origins of a Beta Cell
By: James LeFevre
Uncovering the mechanisms of beta cell regeneration are instrumental for the goal of restoring beta cell function in type 1 diabetes (T1D). Unsurprisingly, like many areas of T1D research, pancreatic beta cell regeneration research possesses mystery and controversy. However, this isn’t just a Scooby-Doo mystery, here we have a full blown Sherlock Holmes case to crack with much uncertainty surrounding beta cell regeneration—so let’s get crackin’!
Beta Cell Regeneration
Guney and colleagues provide the current evidence and controversies for each mechanism of beta cell regeneration. The regeneration of beta cells is categorized by either proliferation of existing beta cells, neogenesis of beta cells from progenitors, or transdifferentiation of non-beta cells into beta cells. Proliferation of beta cells occurs the most during pancreatic development and can be enhanced by metabolic stressors like obesity. Beta cell proliferation declines markedly early in life where adults have low rates of beta cell proliferation. Beta cell neogenesis progenitors occur during embryonic development, however, whether this occurs in adult pancreata endogenously or only under certain pathological conditions is uncertain. Transdifferentiation of non-beta cells may also occur, but the conditions most conducive to transdifferentiation are uncertain.
New Insights on New Beta Cells
With further investigation, Zhao and colleagues developed a genetic tracing system to better understand beta cell regeneration and conditions that contribute to new beta cell formation. The researchers found that insulin-negative cells do not generate new beta cells in the adult pancreas during homeostasis, pregnancy, or injury. Conversely, non-beta cells can generate insulin-positive cells after extreme genetic ablation of beta cells, which is consistent with a transdifferentiation hypothesis. Ultimately, their results suggest that progenitor cells do not contribute to new beta-cell formation under physiological conditions.
Understanding beta cell regeneration is important for the development of new T1D therapies. Beta cell regeneration may occur through proliferation of beta cells, transdifferentiation, or neogenesis. Further understanding of how these processes contribute to new beta cell formation will provide a new outlet for regenerating the beta cell function that is lost in T1D.
- Guney, M. A., Lorberbaum, D. S., & Sussel, L. (2020). Pancreatic β cell regeneration: To β or not to β. Current Opinion in Physiology, 14, 13–20. https://doi.org/10.1016/j.cophys.2019.10.019
- Zhao, H., Huang, X., Liu, Z., Pu, W., Lv, Z., He, L., Li, Y., Zhou, Q., Lui, K. O., & Zhou, B. (2021). Pre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas. Nature Metabolism, 3(3), 352–365. https://doi.org/10.1038/s42255-021-00364-0