A central role for GRB10 in regulation of islet function in man.
PLoS Genet
; 10(4): e1004235, 2014 Apr.
Article
in En
| MEDLINE
| ID: mdl-24699409
ABSTRACT
Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Islets of Langerhans
/
GRB10 Adaptor Protein
Type of study:
Systematic_reviews
Limits:
Humans
/
Male
/
Middle aged
Language:
En
Journal:
PLoS Genet
Journal subject:
GENETICA
Year:
2014
Type:
Article