High-throughput screening and bioinformatic analysis to ascertain compounds that prevent saturated fatty acid-induced ß-cell apoptosis.
Biochem Pharmacol
; 138: 140-149, 2017 08 15.
Article
em En
| MEDLINE
| ID: mdl-28522407
Pancreatic ß-cell lipotoxicity is a central feature of the pathogenesis of type 2 diabetes. To study the mechanism by which fatty acids cause ß-cell death and develop novel approaches to prevent it, a high-throughput screen on the ß-cell line INS1 was carried out. The cells were exposed to palmitate to induce cell death and compounds that reversed palmitate-induced cytotoxicity were ascertained. Hits from the screen were analyzed by an increasingly more stringent testing funnel, ending with studies on primary human islets treated with palmitate. MAP4K4 inhibitors, which were not part of the screening libraries but were ascertained by a bioinformatics analysis, and the endocannabinoid anandamide were effective at inhibiting palmitate-induced apoptosis in INS1 cells as well as primary rat and human islets. These targets could serve as the starting point for the development of therapeutics for type 2 diabetes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
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Apoptose
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Peptídeos e Proteínas de Sinalização Intracelular
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Inibidores de Proteínas Quinases
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Inibidores Enzimáticos
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Células Secretoras de Insulina
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Inibidores de Fosfoinositídeo-3 Quinase
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Hipoglicemiantes
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2017
Tipo de documento:
Article