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Current Diabetes Reports
Published in: Current Diabetes Reports 6/2013

01-12-2013 | Genetics (TM Frayling, Section Editor)

Moving on from GWAS: Functional Studies on the G6PC2 Gene Implicated in the Regulation of Fasting Blood Glucose

Author: Richard M. O’Brien

Published in: Current Diabetes Reports | Issue 6/2013

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Abstract

Genome-wide association studies (GWAS) have shown that single-nucleotide polymorphisms (SNPs) in G6PC2 are the most important common determinants of variations in fasting blood glucose (FBG) levels. Molecular studies examining the functional impact of these SNPs on G6PC2 gene transcription and splicing suggest that they affect FBG by directly modulating G6PC2 expression. This conclusion is supported by studies on G6pc2 knockout (KO) mice showing that G6pc2 represents a negative regulator of basal glucose-stimulated insulin secretion that acts by hydrolyzing glucose-6-phosphate, thereby reducing glycolytic flux and opposing the action of glucokinase. Suppression of G6PC2 activity might, therefore, represent a novel therapy for lowering FBG and the risk of cardiovascular-associated mortality. GWAS and G6pc2 KO mouse studies also suggest that G6PC2 affects other aspects of beta cell function. The evolutionary benefit conferred by G6PC2 remains unclear, but it is unlikely to be related to its ability to modulate FBG.
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Metadata
Title
Moving on from GWAS: Functional Studies on the G6PC2 Gene Implicated in the Regulation of Fasting Blood Glucose
Author
Richard M. O’Brien
Publication date
01-12-2013
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 6/2013
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-013-0422-8

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