Reduction of mRNA m6A associates with glucose metabolism via YTHDC1 in human and mice.
Diabetes Res Clin Pract
; 198: 110607, 2023 Apr.
Article
en En
| MEDLINE
| ID: mdl-36878322
ABSTRACT
AIMS:
N6-methyladenosine (m6A) in mRNA is involved in glucose metabolism. Our goal is to investigate the relationship of glucose metabolism, m6A and YTH domain-containing protein 1 (YTHDC1), a binding protein to m6A, in the development of type 2 diabetes (T2D).METHODS:
HPLC-MS/MS and qRT-PCR were used to quantify m6A and YTHDC1 levels in white blood cells from patients with T2D and healthy individuals. MIP-CreERT and tamoxifen treatment were used to create ß-cell Ythdc1 knockout mice (ßKO). m6A sequencing and RNA sequencing were performed in wildtype/ßKO islets and MIN6 cells to identify the differential genes.RESULTS:
In T2D patients, both of m6A and YTHDC1 levels were reduced and associated with fasting glucose. Deletion of Ythdc1 resulted in glucose intolerance and diabetes due to decreased insulin secretion, even though ß-cell mass in ßKO mice was comparable to wildtype mice. Moreover, Ythdc1 was shown to bind to SRSF3 (serine/arginine-rich splicing factor 3) and CPSF6 (cleavage and polyadenylation specific factor 6) in ß-cells.CONCLUSIONS:
Our data suggested that YTHDC1 may regulate mRNA splicing and export by interacting with SRSF3 and CPSF6 to modulate glucose metabolism via regulating insulin secretion, implying YTHDC1 might be a novel potential target for lowing glucose.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Diabetes Res Clin Pract
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China