GPR142 prompts glucagon-like Peptide-1 release from islets to improve ß cell function.
Mol Metab
; 11: 205-211, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29506910
ABSTRACT
OBJECTIVE:
GPR142 agonists are being pursued as novel diabetes therapies by virtue of their insulin secretagogue effects. But it is undetermined whether GPR142's functions in pancreatic islets are limited to regulating insulin secretion. The current study expands research on its action. METHODS ANDRESULTS:
We demonstrated by in situ hybridization and immunostaining that GPR142 is expressed not only in ß cells but also in a subset of α cells. Stimulation of GPR142 by a selective agonist increased glucagon secretion in both human and mouse islets. More importantly, the GPR142 agonist also potentiated glucagon-like peptide-1 (GLP-1) production and its release from islets through a mechanism that involves upregulation of prohormone convertase 1/3 expression. Strikingly, stimulation of insulin secretion and increase in insulin content via GPR142 engagement requires intact GLP-1 receptor signaling. Furthermore, GPR142 agonist increased ß cell proliferation and protected both mouse and human islets against stress-induced apoptosis.CONCLUSIONS:
Collectively, we provide here evidence that local GLP-1 release from α cells defines GPR142's beneficial effects on improving ß cell function and mass, and we propose that GPR142 agonism may have translatable and durable efficacy for the treatment of type 2 diabetes.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
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Células Secretoras de Glucagon
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Células Secretoras de Insulina
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Peptídeo 1 Semelhante ao Glucagon
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article