Targeted pharmacological therapy restores β-cell function for diabetes remission

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Targeted pharmacological therapy restores β-cell function for diabetes remission. / Sachs, Stephan; Bastidas-Ponce, Aimée; Tritschler, Sophie; Bakhti, Mostafa; Böttcher, Anika; Sánchez-Garrido, Miguel A; Tarquis-Medina, Marta; Kleinert, Maximilian; Fischer, Katrin; Jall, Sigrid; Harger, Alexandra; Bader, Erik; Roscioni, Sara; Ussar, Siegfried; Feuchtinger, Annette; Yesildag, Burcak; Neelakandhan, Aparna; Jensen, Christine B; Cornu, Marion; Yang, Bin; Finan, Brian; DiMarchi, Richard D; Tschöp, Matthias H; Theis, Fabian J; Hofmann, Susanna M.; Müller, Timo D; Lickert, Heiko.

I: Nature Metabolism, Bind 2, Nr. 2, 2020, s. 192-209.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Sachs, S, Bastidas-Ponce, A, Tritschler, S, Bakhti, M, Böttcher, A, Sánchez-Garrido, MA, Tarquis-Medina, M, Kleinert, M, Fischer, K, Jall, S, Harger, A, Bader, E, Roscioni, S, Ussar, S, Feuchtinger, A, Yesildag, B, Neelakandhan, A, Jensen, CB, Cornu, M, Yang, B, Finan, B, DiMarchi, RD, Tschöp, MH, Theis, FJ, Hofmann, SM, Müller, TD & Lickert, H 2020, 'Targeted pharmacological therapy restores β-cell function for diabetes remission', Nature Metabolism, bind 2, nr. 2, s. 192-209. https://doi.org/10.1038/s42255-020-0171-3

APA

Sachs, S., Bastidas-Ponce, A., Tritschler, S., Bakhti, M., Böttcher, A., Sánchez-Garrido, M. A., ... Lickert, H. (2020). Targeted pharmacological therapy restores β-cell function for diabetes remission. Nature Metabolism, 2(2), 192-209. https://doi.org/10.1038/s42255-020-0171-3

Vancouver

Sachs S, Bastidas-Ponce A, Tritschler S, Bakhti M, Böttcher A, Sánchez-Garrido MA o.a. Targeted pharmacological therapy restores β-cell function for diabetes remission. Nature Metabolism. 2020;2(2):192-209. https://doi.org/10.1038/s42255-020-0171-3

Author

Sachs, Stephan ; Bastidas-Ponce, Aimée ; Tritschler, Sophie ; Bakhti, Mostafa ; Böttcher, Anika ; Sánchez-Garrido, Miguel A ; Tarquis-Medina, Marta ; Kleinert, Maximilian ; Fischer, Katrin ; Jall, Sigrid ; Harger, Alexandra ; Bader, Erik ; Roscioni, Sara ; Ussar, Siegfried ; Feuchtinger, Annette ; Yesildag, Burcak ; Neelakandhan, Aparna ; Jensen, Christine B ; Cornu, Marion ; Yang, Bin ; Finan, Brian ; DiMarchi, Richard D ; Tschöp, Matthias H ; Theis, Fabian J ; Hofmann, Susanna M. ; Müller, Timo D ; Lickert, Heiko. / Targeted pharmacological therapy restores β-cell function for diabetes remission. I: Nature Metabolism. 2020 ; Bind 2, Nr. 2. s. 192-209.

Bibtex

@article{f5fb909706c546c794b1f08029628cb0,
title = "Targeted pharmacological therapy restores β-cell function for diabetes remission",
abstract = "Dedifferentiation of insulin-secreting β cells in the islets of Langerhans has been proposed to be a major mechanism of β-cell dysfunction. Whether dedifferentiated β cells can be targeted by pharmacological intervention for diabetes remission, and ways in which this could be accomplished, are unknown as yet. Here we report the use of streptozotocin-induced diabetes to study β-cell dedifferentiation in mice. Single-cell RNA sequencing (scRNA-seq) of islets identified markers and pathways associated with β-cell dedifferentiation and dysfunction. Single and combinatorial pharmacology further show that insulin treatment triggers insulin receptor pathway activation in β cells and restores maturation and function for diabetes remission. Additional β-cell selective delivery of oestrogen by Glucagon-like peptide-1 (GLP-1–oestrogen conjugate) decreases daily insulin requirements by 60{\%}, triggers oestrogen-specific activation of the endoplasmic-reticulum-associated protein degradation system, and further increases β-cell survival and regeneration. GLP-1–oestrogen also protects human β cells against cytokine-induced dysfunction. This study not only describes mechanisms of β-cell dedifferentiation and regeneration, but also reveals pharmacological entry points to target dedifferentiated β cells for diabetes remission.",
author = "Stephan Sachs and Aim{\'e}e Bastidas-Ponce and Sophie Tritschler and Mostafa Bakhti and Anika B{\"o}ttcher and S{\'a}nchez-Garrido, {Miguel A} and Marta Tarquis-Medina and Maximilian Kleinert and Katrin Fischer and Sigrid Jall and Alexandra Harger and Erik Bader and Sara Roscioni and Siegfried Ussar and Annette Feuchtinger and Burcak Yesildag and Aparna Neelakandhan and Jensen, {Christine B} and Marion Cornu and Bin Yang and Brian Finan and DiMarchi, {Richard D} and Tsch{\"o}p, {Matthias H} and Theis, {Fabian J} and Hofmann, {Susanna M.} and M{\"u}ller, {Timo D} and Heiko Lickert",
note = "CURIS 2020 NEXS 087",
year = "2020",
doi = "10.1038/s42255-020-0171-3",
language = "English",
volume = "2",
pages = "192--209",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer Nature",
number = "2",

}

RIS

TY - JOUR

T1 - Targeted pharmacological therapy restores β-cell function for diabetes remission

AU - Sachs, Stephan

AU - Bastidas-Ponce, Aimée

AU - Tritschler, Sophie

AU - Bakhti, Mostafa

AU - Böttcher, Anika

AU - Sánchez-Garrido, Miguel A

AU - Tarquis-Medina, Marta

AU - Kleinert, Maximilian

AU - Fischer, Katrin

AU - Jall, Sigrid

AU - Harger, Alexandra

AU - Bader, Erik

AU - Roscioni, Sara

AU - Ussar, Siegfried

AU - Feuchtinger, Annette

AU - Yesildag, Burcak

AU - Neelakandhan, Aparna

AU - Jensen, Christine B

AU - Cornu, Marion

AU - Yang, Bin

AU - Finan, Brian

AU - DiMarchi, Richard D

AU - Tschöp, Matthias H

AU - Theis, Fabian J

AU - Hofmann, Susanna M.

AU - Müller, Timo D

AU - Lickert, Heiko

N1 - CURIS 2020 NEXS 087

PY - 2020

Y1 - 2020

N2 - Dedifferentiation of insulin-secreting β cells in the islets of Langerhans has been proposed to be a major mechanism of β-cell dysfunction. Whether dedifferentiated β cells can be targeted by pharmacological intervention for diabetes remission, and ways in which this could be accomplished, are unknown as yet. Here we report the use of streptozotocin-induced diabetes to study β-cell dedifferentiation in mice. Single-cell RNA sequencing (scRNA-seq) of islets identified markers and pathways associated with β-cell dedifferentiation and dysfunction. Single and combinatorial pharmacology further show that insulin treatment triggers insulin receptor pathway activation in β cells and restores maturation and function for diabetes remission. Additional β-cell selective delivery of oestrogen by Glucagon-like peptide-1 (GLP-1–oestrogen conjugate) decreases daily insulin requirements by 60%, triggers oestrogen-specific activation of the endoplasmic-reticulum-associated protein degradation system, and further increases β-cell survival and regeneration. GLP-1–oestrogen also protects human β cells against cytokine-induced dysfunction. This study not only describes mechanisms of β-cell dedifferentiation and regeneration, but also reveals pharmacological entry points to target dedifferentiated β cells for diabetes remission.

AB - Dedifferentiation of insulin-secreting β cells in the islets of Langerhans has been proposed to be a major mechanism of β-cell dysfunction. Whether dedifferentiated β cells can be targeted by pharmacological intervention for diabetes remission, and ways in which this could be accomplished, are unknown as yet. Here we report the use of streptozotocin-induced diabetes to study β-cell dedifferentiation in mice. Single-cell RNA sequencing (scRNA-seq) of islets identified markers and pathways associated with β-cell dedifferentiation and dysfunction. Single and combinatorial pharmacology further show that insulin treatment triggers insulin receptor pathway activation in β cells and restores maturation and function for diabetes remission. Additional β-cell selective delivery of oestrogen by Glucagon-like peptide-1 (GLP-1–oestrogen conjugate) decreases daily insulin requirements by 60%, triggers oestrogen-specific activation of the endoplasmic-reticulum-associated protein degradation system, and further increases β-cell survival and regeneration. GLP-1–oestrogen also protects human β cells against cytokine-induced dysfunction. This study not only describes mechanisms of β-cell dedifferentiation and regeneration, but also reveals pharmacological entry points to target dedifferentiated β cells for diabetes remission.

UR - http://www.scopus.com/inward/record.url?scp=85079823155&partnerID=8YFLogxK

U2 - 10.1038/s42255-020-0171-3

DO - 10.1038/s42255-020-0171-3

M3 - Journal article

AN - SCOPUS:85079823155

VL - 2

SP - 192

EP - 209

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 2

ER -

ID: 238369497