Optical Control of Insulin Secretion Using an Incretin Switch.
Angew Chem Int Ed Engl
; 54(51): 15565-9, 2015 Dec 14.
Article
em En
| MEDLINE
| ID: mdl-26585495
ABSTRACT
Incretin mimetics are set to become a mainstay of typeâ
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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Base de dados:
MEDLINE
Assunto principal:
Incretinas
/
Liraglutida
/
Insulina
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article