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Diabetes: Many Faces of the Disease | EK18


EK18-EPOSTER-BARZOWSKA-AGATA - Novel Dyrk1A inhibitors as a potential therapeutic agents


Feb 1, 2021 12:00am ‐ Feb 1, 2021 12:00am

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Novel Dyrk1A inhibitors as a potential therapeutic agents Novel Dyrk1A inhibitors as a potential therapeutic agents Agata Barzowska, Barbara Pucelik, Alex Matsuda, Anna Czarna Jagiellonian University, Małopolska Centre of Biotechnology, Gronostajowa 7A, 30-387, Kraków, Poland Small molecules targeting protein kinases are among the best tools for advanced therapy. They allow us to understand the mechanisms of disease. In recent years, the role of DYRK1A kinase in beta-cell proliferation and its possible use as a therapeutic target in the treatment of diabetes has been demonstrated [1]. Consequently, novel compounds dedicated to this kinase are being sought. The inhibitors under investigation are potential regulatory agents that restore pancreatic β-cell mass, secretory, and organ regulatory functions. Moreover, patient-derived induced pluripotent stem cells (iPSCs) allow screening for various diseases and facilitate the discovery of new drugs [2,3]. The optimal inhibitor will restore the blood glucose levels and provide the conditions necessary for the growth and function of the host and new beta cells derived from iPSCs. The presented study proved that tested inhibitors increase the beta-cell proliferation, homing, engraftment, and thus regulate the blood glucose levels. The functionality of pancreatic islets derived from iPSC was also confirmed after treatment with selected inhibitors. Islets were isolated from BALB/c mice, and insulin secretion was determined after treatment with the tested compounds. The NCN financed this work within the grant no 2019/34/E/NZ1/00467 [1] Wang P, Alvarez-Perez J-C, Felsenfeld DP, et al. A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nat Med. 2015;21:383–388. [2] Pagliuca FW, Millman JR, Gürtler M, et al. Generation of functional human pancreatic β cells in vitro. Cell. 2014;159:428–439. [3] Russ HA, Parent AV, Ringler JJ, et al. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J. 2015;34:1759–1772.

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