miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.
J Diabetes Investig
; 13(4): 617-627, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-34800086
ABSTRACT
AIM/INTRODUCTION:
Obesity is considered an important risk factor for many metabolic disorders, especially type 2 diabetes mellitus, and microRNAs (miRNAs) play a vital role in the development of type 2 diabetes mellitus. Therefore, we conducted this study to investigate the role of miR-4431 in the obesity-associated pathobiology of type 2 diabetes mellitus. MATERIALS ANDMETHODS:
Subjects were divided into normal control (n = 36), obese (n = 36), and type 2 diabetes mellitus (n = 12) groups, and serum miR-4431 levels were analyzed. Adenovirus-vectored miR-4431 mimic or sponge was intraperitoneally injected into the normal diet group and the high-fat diet group (HFD) mice to investigate glucose tolerance, insulin sensitivity, and lipid levels. The downstream target genes of miR-4431 were predicted using bioinformatics, and they were verified in vitro.RESULTS:
Serum miR-4431 levels were significantly high in obese and type 2 diabetes mellitus individuals, and positively correlated with the body mass index and fasting plasma glucose levels. In HFD mice, miR-4431 levels in the serum, white adipose tissue, and liver were significantly increased. Moreover, miR-4431 impaired glucose tolerance, insulin sensitivity, and lipid metabolism in mice. Bioinformatic prediction suggested that TRIP10 and PRKD1 could be the downstream target genes of miR-4431. The HFD mice showed a remarkable reduction in the mRNA levels of TRIP10 and PRKD1 in the liver, which were countered by blocking miR-4431. In HepG2 and L02 cells, miR-4431 could downregulate TRIP10 and PRKD1 while blocking glucose uptake. The luciferase reporter assay showed that miR-4431 could bind TRIP10 and PRKD1 3'-UTR.CONCLUSION:
miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
MicroARNs
/
Diabetes Mellitus Tipo 2
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Diabetes Investig
Año:
2022
Tipo del documento:
Article
País de afiliación:
China