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Scientific article
English

Combined inhibition of menin-MLL interaction and TGF-β signaling induces replication of human pancreatic beta cells

Published inEuropean Journal of Cell Biology, vol. 99, no. 5, 151094
Publication date2020
Abstract

Both type 1 and type 2 diabetes are associated with hyperglycemia and loss of functional beta cell mass. Inducing proliferation of preexisting beta cells is an approach to increase the numbers of beta cells. In this study, we examined a panel of selected small molecules for their proliferation-inducing effects on human pancreatic beta cells. Our results demonstrated that a small molecule inhibitor of the menin-MLL interaction (MI-2) and small molecule inhibitors of TGF-β signaling (SB431542, LY2157299, or LY364947) synergistically increased ex vivo replication of human beta cells. We showed that this increased proliferation did not affect insulin production, as a pivotal indication of beta cell function. We further provided evidence which suggested that menin-MLL and TGF-β inhibition cooperated through downregulation of cell cycle inhibitors CDKN1A, CDKN1B, and CDKN2C. Our findings might provide a new option for extending the pharmacological repertoire for induction of beta cell proliferation as a potential therapeutic approach for diabetes.

Keywords
  • Combined inhibition of menin-MLL
Citation (ISO format)
PAHLAVANNESHAN, Saghar et al. Combined inhibition of menin-MLL interaction and TGF-β signaling induces replication of human pancreatic beta cells. In: European Journal of Cell Biology, 2020, vol. 99, n° 5, p. 151094. doi: 10.1016/j.ejcb.2020.151094
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Identifiers
ISSN of the journal0171-9335
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Technical informations

Creation08/03/2020 1:43:00 PM
First validation08/03/2020 1:43:00 PM
Update time03/15/2023 10:25:43 PM
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