DYRK1A inhibitors leucettines and TGF-β inhibitor additively stimulate insulin production in beta cells, organoids, and isolated mouse islets.

ABSTRACT: The decreased β-cell mass and impaired β-cell functionality are the primary causes of diabetes mellitus (DM). Nevertheless, the underlying molecular mechanisms by which β-cell growth and function are controlled are not fully understood. In this work, we show that leucettines, known to be DYRK1A kinase inhibitors, can improve glucose-stimulated insulin secretion (GSIS) in rodent β-cells and isolated islets, as well as in hiPSC-derived β-cells islets. We confirm that DYRK1A is expressed in murine insulinoma cells MIN6. In addition, we found that treatment with selected leucettines stimulates proliferation of β-cells and promotes MIN6 cell cycle progression to the G2/M phase. This effect is also confirmed by increased levels of cyclin D1, which is highly responsive to proliferative signals. A

SUBMITTER: Pucelik B 

PROVIDER: S-EPMC10191338 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature