naa a22 4500 510779484 CHVBK 20180411083242.0 cr unu---uuuuu 180411e20131201xx s 000 0 eng 10.1007/s11892-013-0422-8 doi (NATIONALLICENCE)springer-10.1007/s11892-013-0422-8 O'Brien Richard Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 37232, Nashville, TN, USA aut Moving on from GWAS: Functional Studies on the G6PC2 Gene Implicated in the Regulation of Fasting Blood Glucose [Elektronische Daten] [Richard O'Brien] 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. Springer Science+Business Media New York, 2013 Islet nationallicence Glucose nationallicence Glucose-6-phosphatase nationallicence Insulin nationallicence Secretion nationallicence Mouse nationallicence Genome-wide association studies nationallicence GWAS nationallicence G6PC2 gene nationallicence Fasting blood glucose nationallicence Functional studies nationallicence Current Diabetes Reports Springer US; http://www.springer-ny.com 13/6(2013-12-01), 768-777 1534-4827 13:6<768 2013 13 11892 https://doi.org/10.1007/s11892-013-0422-8 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11892-013-0422-8 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- O'Brien Richard Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 37232, Nashville, TN, USA aut NATIONALLICENCE 773 0- Current Diabetes Reports Springer US; http://www.springer-ny.com 13/6(2013-12-01), 768-777 1534-4827 13:6<768 2013 13 11892 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer