Optical Control of Insulin Secretion Using an Incretin Switch

Johannes Broichhagen; Tom Podewin; Helena Meyer-berg; Yorrick Von Ohlen; Natalie R. Johnston; Ben J. Jones; Stephen R. Bloom; Guy A. Rutter; Anja Hoffmann-röder; David J. Hodson; Dirk Trauner

doi:10.1002/anie.201506384

Optical Control of Insulin Secretion Using an Incretin Switch

Johannes Broichhagen, Tom Podewin, Helena Meyer-berg, Yorrick Von Ohlen, Natalie R. Johnston, Ben J. Jones, Stephen R. Bloom, Guy A. Rutter, Anja Hoffmann-röder, David J. Hodson, Dirk Trauner

Medical and Dental Sciences

Research output: Contribution to journal › Article › peer-review

51 Citations (Scopus)

92 Downloads (Pure)

Abstract

Incretin mimetics are set to become a mainstay of type 2 diabetes treatment. By acting on the pancreas and brain, they potentiate insulin secretion and induce weight loss to preserve normoglycemia. Despite this, incretin therapy has been associated with off-target effects, including nausea and gastrointestinal disturbance. A novel photoswitchable incretin mimetic based upon the specific glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was designed, synthesized, and tested. This peptidic compound, termed LirAzo, possesses an azobenzene photoresponsive element, affording isomer-biased GLP-1R signaling as a result of differential activation of second messenger pathways in response to light. While the trans isomer primarily engages calcium influx, the cis isomer favors cAMP generation. LirAzo thus allows optical control of insulin secretion and cell survival.

Original language	English
Pages (from-to)	15565–15569
Journal	Angewandte Chemie (International Edition)
Volume	54
Issue number	51
Early online date	2 Nov 2015
DOIs	https://doi.org/10.1002/anie.201506384
Publication status	Published - 14 Dec 2015

Keywords

beta cells
insulin
liraglutide
photopharmacology
type 2 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Broichhagen, J., Podewin, T., Meyer-berg, H., Von Ohlen, Y., Johnston, N. R., Jones, B. J., Bloom, S. R., Rutter, G. A., Hoffmann-röder, A., Hodson, D. J., & Trauner, D. (2015). Optical Control of Insulin Secretion Using an Incretin Switch. Angewandte Chemie (International Edition) , 54(51), 15565–15569. Advance online publication. https://doi.org/10.1002/anie.201506384

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abstract = "Incretin mimetics are set to become a mainstay of type 2 diabetes treatment. By acting on the pancreas and brain, they potentiate insulin secretion and induce weight loss to preserve normoglycemia. Despite this, incretin therapy has been associated with off-target effects, including nausea and gastrointestinal disturbance. A novel photoswitchable incretin mimetic based upon the specific glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was designed, synthesized, and tested. This peptidic compound, termed LirAzo, possesses an azobenzene photoresponsive element, affording isomer-biased GLP-1R signaling as a result of differential activation of second messenger pathways in response to light. While the trans isomer primarily engages calcium influx, the cis isomer favors cAMP generation. LirAzo thus allows optical control of insulin secretion and cell survival.",

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AU - Podewin, Tom

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AU - Johnston, Natalie R.

AU - Jones, Ben J.

AU - Bloom, Stephen R.

AU - Rutter, Guy A.

AU - Hoffmann-röder, Anja

AU - Hodson, David J.

AU - Trauner, Dirk

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AB - Incretin mimetics are set to become a mainstay of type 2 diabetes treatment. By acting on the pancreas and brain, they potentiate insulin secretion and induce weight loss to preserve normoglycemia. Despite this, incretin therapy has been associated with off-target effects, including nausea and gastrointestinal disturbance. A novel photoswitchable incretin mimetic based upon the specific glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide was designed, synthesized, and tested. This peptidic compound, termed LirAzo, possesses an azobenzene photoresponsive element, affording isomer-biased GLP-1R signaling as a result of differential activation of second messenger pathways in response to light. While the trans isomer primarily engages calcium influx, the cis isomer favors cAMP generation. LirAzo thus allows optical control of insulin secretion and cell survival.

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KW - insulin

KW - liraglutide

KW - photopharmacology

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ER -

Optical Control of Insulin Secretion Using an Incretin Switch

Abstract

Keywords

UN SDGs

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