CONTEXT: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are associated with fasting glucose and insulin secretion. These SNPs are not associated with type 2 diabetes risk. OBJECTIVE: Our objective was to investigate whether the impact of the SNP on variables of glucose-stimulated insulin secretion is influenced by glucose tolerance status. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: In this cross-sectional study, we genotyped 1505 healthy Caucasian subjects [normal glucose tolerance (NGT), 1098; impaired glucose tolerance (IGT)/impaired fasting glucose (IFG), 407] for SNP rs560887 within the G6PC2 locus. A subgroup of 326 subjects underwent an iv glucose tolerance test, and 512 participants took part in a hyperinsulinemic-euglycemic clamp. For replication, SNP rs560887 was genotyped in 457 subjects (NGT, 265; IGT, 192) from four independent German and Dutch studies who underwent a hyperglycemic clamp. MAIN OUTCOME MEASURE: Insulin secretion was evaluated. RESULTS: Carriers of the major G-allele exhibited increased fasting glycemia (P<0.0001). Insulin sensitivity and secretion were not associated with the SNP (P≥0.06). Glucose tolerance status and genotype interacted on insulin secretion (P=0.036), such that in NGT subjects, the minor A-allele of rs560887 was associated with decreased insulinogenic index (P=0.044), which was not the case in subjects with IFG/IGT (P=1.0). During the iv glucose tolerance test, an association of A-allele carriers with decreased first-phase insulin secretion was also observed only in NGT subjects (P=0.0053). Likewise, in the hyperglycemic clamp group, the A-allele was associated with decreased first-phase insulin secretion only in the NGT group (P=0.022) but not in the IGT group. CONCLUSIONS: The effects of hyperglycemia on insulin secretion override the more subtle effects of genetic variation in the G6PC2 locus on insulin secretion.
CONTEXT: Single-nucleotide polymorphisms (SNPs) within the G6PC2 locus are associated with fasting glucose and insulin secretion. These SNPs are not associated with type 2 diabetes risk. OBJECTIVE: Our objective was to investigate whether the impact of the SNP on variables of glucose-stimulated insulin secretion is influenced by glucose tolerance status. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: In this cross-sectional study, we genotyped 1505 healthy Caucasian subjects [normal glucose tolerance (NGT), 1098; impaired glucose tolerance (IGT)/impaired fasting glucose (IFG), 407] for SNP rs560887 within the G6PC2 locus. A subgroup of 326 subjects underwent an iv glucose tolerance test, and 512 participants took part in a hyperinsulinemic-euglycemic clamp. For replication, SNP rs560887 was genotyped in 457 subjects (NGT, 265; IGT, 192) from four independent German and Dutch studies who underwent a hyperglycemic clamp. MAIN OUTCOME MEASURE: Insulin secretion was evaluated. RESULTS: Carriers of the major G-allele exhibited increased fasting glycemia (P<0.0001). Insulin sensitivity and secretion were not associated with the SNP (P≥0.06). Glucose tolerance status and genotype interacted on insulin secretion (P=0.036), such that in NGT subjects, the minor A-allele of rs560887 was associated with decreased insulinogenic index (P=0.044), which was not the case in subjects with IFG/IGT (P=1.0). During the iv glucose tolerance test, an association of A-allele carriers with decreased first-phase insulin secretion was also observed only in NGT subjects (P=0.0053). Likewise, in the hyperglycemic clamp group, the A-allele was associated with decreased first-phase insulin secretion only in the NGT group (P=0.022) but not in the IGT group. CONCLUSIONS: The effects of hyperglycemia on insulin secretion override the more subtle effects of genetic variation in the G6PC2 locus on insulin secretion.
Authors: Kayla A Boortz; Kristen E Syring; Lynley D Pound; Huan Mo; Lisa Bastarache; James K Oeser; Owen P McGuinness; Joshua C Denny; Richard M O'Brien Journal: J Mol Endocrinol Date: 2017-01-25 Impact factor: 5.098
Authors: Kayla A Boortz; Kristen E Syring; Rebecca A Lee; Chunhua Dai; James K Oeser; Owen P McGuinness; Jen-Chywan Wang; Richard M O'Brien Journal: Endocrinology Date: 2016-09-21 Impact factor: 4.736
Authors: Lynley D Pound; James K Oeser; Tracy P O'Brien; Yingda Wang; Chandler J Faulman; Prasanna K Dadi; David A Jacobson; John C Hutton; Owen P McGuinness; Masakazu Shiota; Richard M O'Brien Journal: Diabetes Date: 2012-12-28 Impact factor: 9.461
Authors: Robert Wagner; Katarzyna Dudziak; Silke A Herzberg-Schäfer; Fausto Machicao; Norbert Stefan; Harald Staiger; Hans-Ulrich Häring; Andreas Fritsche Journal: PLoS One Date: 2011-08-22 Impact factor: 3.240
Authors: C Zusi; E Rinaldi; S Bonetti; M L Boselli; E Trabetti; G Malerba; E Bonora; R C Bonadonna; M Trombetta Journal: J Endocrinol Invest Date: 2021-06-14 Impact factor: 4.256