Loss of Znt8 function in diabetes mellitus: risk or benefit?
Mol Cell Biochem
; 476(7): 2703-2718, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33666829
ABSTRACT
The zinc transporter 8 (ZnT8) plays an essential role in zinc homeostasis inside pancreatic ß cells, its function is related to the stabilization of insulin hexameric form. Genome-wide association studies (GWAS) have established a positive and negative relationship of ZnT8 variants with type 2 diabetes mellitus (T2DM), exposing a dual and controversial role. The first hypotheses about its role in T2DM indicated a higher risk of developing T2DM for loss of function; nevertheless, recent GWAS of ZnT8 loss-of-function mutations in humans have shown protection against T2DM. With regard to the ZnT8 role in T2DM, most studies have focused on rodent models and common high-risk variants; however, considerable differences between human and rodent models have been found and the new approaches have included lower-frequency variants as a tool to clarify gene functions, allowing a better understanding of the disease and offering possible therapeutic targets. Therefore, this review will discuss the physiological effects of the ZnT8 variants associated with a major and lower risk of T2DM, emphasizing the low- and rare-frequency variants.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Transportador 8 de Zinco
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
México