GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration

Courtney Ackeifi; Peng Wang; Esra Karakose; Jocelyn E. Manning Fox; Bryan J. González; Hongtao Liu; Jessica Wilson; Ethan Swartz; Cecilia Berrouet; Yansui Li; Kunal Kumar; Patrick E. MacDonald; Roberto Sanchez; Bernard Thorens; Robert DeVita; Dirk Homann; Dieter Egli; Donald K. Scott; Adolfo Garcia-Ocaña; Andrew F. Stewart

doi:10.1126/scitranslmed.aaw9996

Research ArticleRegenerative Medicine

GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration

Courtney Ackeifi ¹,*,
Peng Wang¹,*,
Esra Karakose¹,*,
Jocelyn E. Manning Fox²,
Bryan J. González³,
Hongtao Liu¹,
Jessica Wilson¹,
Ethan Swartz¹,
Cecilia Berrouet¹,
Yansui Li¹,
Kunal Kumar⁴,
Patrick E. MacDonald²,
Roberto Sanchez⁴,
Bernard Thorens⁵,
Robert DeVita⁴,
Dirk Homann¹,
Dieter Egli³,
Donald K. Scott¹,
Adolfo Garcia-Ocaña ¹ and
Andrew F. Stewart ¹,†

¹Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
³Naomi Berrie Diabetes Center and Columbia Stem Cell Center, Columbia University, New York, NY 10032, USA.
⁴Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁵Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.

↵†Corresponding author. Email: andrew.stewart{at}mssm.edu

↵* These authors contributed equally to this work.

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Science Translational Medicine 12 Feb 2020:
Vol. 12, Issue 530, eaaw9996
DOI: 10.1126/scitranslmed.aaw9996

Courtney Ackeifi

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Peng Wang

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Esra Karakose

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Jocelyn E. Manning Fox

Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.

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Bryan J. González

Naomi Berrie Diabetes Center and Columbia Stem Cell Center, Columbia University, New York, NY 10032, USA.

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Hongtao Liu

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Jessica Wilson

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Ethan Swartz

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Cecilia Berrouet

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Yansui Li

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Kunal Kumar

Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Patrick E. MacDonald

Department of Pharmacology and Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.

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Roberto Sanchez

Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Bernard Thorens

Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.

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Robert DeVita

Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Dirk Homann

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Dieter Egli

Naomi Berrie Diabetes Center and Columbia Stem Cell Center, Columbia University, New York, NY 10032, USA.

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Donald K. Scott

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Adolfo Garcia-Ocaña

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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Andrew F. Stewart

Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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For correspondence: andrew.stewart@mssm.edu

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GLP-1 receptor agonists synergize with DYRK1A inhibitors to potentiate functional human β cell regeneration

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