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

View ORCID ProfileCourtney Ackeifi ¹,*,
Peng Wang¹,*,
Esra Karakose¹,*,
Jocelyn E. Manning Fox²,
View ORCID ProfileBryan J. González³,
Hongtao Liu¹,
View ORCID ProfileJessica Wilson¹,
Ethan Swartz¹,
Cecilia Berrouet¹,
Yansui Li¹,
Kunal Kumar⁴,
View ORCID ProfilePatrick E. MacDonald²,
Roberto Sanchez⁴,
Bernard Thorens⁵,
View ORCID ProfileRobert DeVita⁴,
View ORCID ProfileDirk Homann¹,
Dieter Egli³,
View ORCID ProfileDonald K. Scott¹,
View ORCID ProfileAdolfo Garcia-Ocaña ¹ and
View ORCID ProfileAndrew 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

1Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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ORCID record for Courtney Ackeifi

Peng Wang

1Diabetes, 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

1Diabetes, 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

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

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Bryan J. González

3Naomi Berrie Diabetes Center and Columbia Stem Cell Center, Columbia University, New York, NY 10032, USA.

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ORCID record for Bryan J. González

Hongtao Liu

1Diabetes, 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

1Diabetes, Obesity and Metabolism Institute and Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

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ORCID record for Jessica Wilson

Ethan Swartz

1Diabetes, 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

1Diabetes, 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

1Diabetes, 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

4Department 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

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

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Roberto Sanchez

4Department 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

5Center for Integrative Genomics, University of Lausanne, Lausanne 1015, Switzerland.

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Robert DeVita

4Department 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

1Diabetes, 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

3Naomi Berrie Diabetes Center and Columbia Stem Cell Center, Columbia University, New York, NY 10032, USA.

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Donald K. Scott

1Diabetes, 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

1Diabetes, 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

1Diabetes, 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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