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.

See allHide authors and affiliations

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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Esra Karakose

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jocelyn E. Manning Fox

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Bryan J. González

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Jessica Wilson

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
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.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Cecilia Berrouet

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Yansui Li

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Kunal Kumar

4Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Patrick E. MacDonald

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Patrick E. MacDonald

Roberto Sanchez

4Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Bernard Thorens

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Robert DeVita

4Department of Pharmacological Sciences, and Drug Discovery Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Robert DeVita

Dirk Homann

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Dirk Homann

Dieter Egli

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site

Donald K. Scott

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Donald K. Scott

Adolfo Garcia-Ocaña

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Adolfo Garcia-Ocaña

Andrew F. Stewart

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

Find this author on Google Scholar
Find this author on PubMed
Search for this author on this site
ORCID record for Andrew F. Stewart
For correspondence: andrew.stewart@mssm.edu

Article
Figures & Data
Info & Metrics
eLetters
PDF

Log in to view PDF

via AAAS login

AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Become an AAAS Member
Activate your Account
Purchase Access to Other Journals in the Science Family
Account Help

Log in through your institution

More options

Purchase digital access to this article

Download and print this article for your personal scholarly, research, and educational use.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

View Full Text

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

Log in to view PDF

Log in through your institution

Log in through your institution

More options

Science Translational Medicine

Article Tools