Orotic acid protects pancreatic ß cell by p53 inactivation in diabetic mouse model.
Biochem Biophys Res Commun
; 585: 191-195, 2021 12 31.
Article
em En
| MEDLINE
| ID: mdl-34813979
ABSTRACT
Impairment of pancreatic ß cells is a principal driver of the development of diabetes. Restoring normal insulin release from the ß cells depends on the ATP produced by the intracellular mitochondria. In maintaining mitochondrial function, the tumor suppressor p53 has emerged as a novel regulator of metabolic homeostasis and participates in adaptations to nutritional changes. In this study, we used orotic acid, an intermediate in the pathway for de novo synthesis of the pyrimidine nucleotide, to reduce genotoxicity. Administration of orotic acid reduced p53 activation of MIN6 ß cells and subsequently reduced ß cell death in the db/db mouse. Orotic acid intake helped to maintain the islet size, number of ß cells, and protected insulin secretion in the db/db mouse. In conclusion, orotic acid treatment maintained ß cell function and reduced cell death, and may therefore, be a future therapeutic strategy for the prevention and treatment of diabetes.
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Base de dados:
MEDLINE
Assunto principal:
Ácido Orótico
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Proteína Supressora de Tumor p53
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Diabetes Mellitus Tipo 2
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Modelos Animais de Doenças
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Células Secretoras de Insulina
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article