β cell plasticity governs the adjustment of β cell mass and function to ensure normoglycemia. The study of how β cell mass is controlled and the identification of alternative sources of β cells are active fields of research. β cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major β cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of β cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 week. Five days after IPR, enhanced β cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. β cell mass was fully restored after an additional 2 days. For the 10-day IPI group, β cell and endocrine mass were no longer significantly different from those of the control group at 2 weeks post-IPR. Furthermore, RT qPCR analysis of endocrine structures isolated by laser capture microdissection (LCM) indicated sequentially enhanced expression of the pancreatic transcription factors Beta2/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of β cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.
Nollevaux, M.-C., Rahier, J., Marchandise, J., Thurion, P., Godecharles, S., Van den Steen, G., Jamart, J., Sempoux, C., Jacquemin, P., & Guiot, Y. (2013). Characterization of β cell plasticity mechanisms induced in mice by a transient source of exogenous insulin. American journal of physiology. Endocrinology and metabolism, 304(7), E711-E723. https://doi.org/10.1152/ajpendo.00304.2012 (Original work published 2013)