GLP1R (glucagon-like-peptide-1 incretin receptor), diabetes and obesity phenotypes: An in silico approach revealed new pathogenic variants.
Diabetes Metab Syndr
; 18(2): 102956, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38364583
ABSTRACT
OBJECTIVE:
Glucagon-like peptide-1 receptor belongs to the B family of G protein-coupled receptors, serving as a binding protein in membranes and is widely expressed in human tissues. Upon stimulation by its agonist, the glucagon-like peptide-1, the receptor plays a role in glucose metabolism, enhancing insulin secretion, and regulating appetite in the hypothalamus. Mutations in the glucagon-like peptide-1 receptor gene can lead to physiological changes that may explain phenotypic variations in individuals with obesity and diabetes. Therefore, this study aimed to evaluate missense variants of the glucagon-like peptide-1 receptor gene.METHODS:
Data mining was performed on the single nucleotide polymorphism database, retrieving a total of 16,399 variants. Among them, 356 were missense. These 356 variants were analyzed using the PolyPhen-2 and filtered based on allele frequency, resulting in 6 pathogenic variants.RESULTS:
D344E, A239T, R310Q, R227H, R421P, and R176G were analyzed using four different prediction tools. The D344E and A239T resulted in larger amino acid residues compared to their wild-type counterparts. The D344E showed a slightly destabilized structure, while A239T affected the transmembrane helices. Conversely, the R310Q, R227H, R421P, and R176G resulted in smaller amino acid residues than the wild-type, leading to a loss of positive charge and increased hydrophobicity. Particularly, the R421P, due to the presence of proline, significantly destabilized the α-helix structure and caused severe damage to the receptor.CONCLUSION:
Elucidating the glucagon-like peptide-1 receptor variants and their potentially detrimental effects on receptor functionality can contribute to an understanding of metabolic diseases and the response to available pharmacological treatments.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus
/
Incretinas
Limite:
Humans
Idioma:
En
Revista:
Diabetes Metab Syndr
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil