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The impact of genetic variation in the G6PC2 gene on insulin secretion depends on glycemia.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Heni, Martin Ketterer, Caroline Hart, Leen M. 't Ranta, Felicia Haeften, Timon W. Van Eekhoff, Elisabeth M. V. Dekker, Jaqueline M. Boomsma, Dorret I. Nijpels, Giel Wohlforth, William Curtis Diamant, Michaela Simonis-Bik, Annemarie M. C. Heine, Robert M. Geus, Eco J. C. De Schäfer, Silke A. Machicao, Fausto E. Ullrich, Susanne Thamer, Claus Stefan, Norbert Staiger, Harald Häring, Hans-Ulrich Fritsche, Andreas |
| Copyright Year | 2010 |
| Abstract | 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. |
| Starting Page | 905 |
| Ending Page | 911 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.tweelingenregister.org/fileadmin/user_upload/publicaties/verslaggeving/NTR-publicaties_2010/Heni_JCEM_2010.pdf |
| Alternate Webpage(s) | http://www.tweelingenregister.org/nederlands/verslaggeving/NTR-publicaties_2010/Heni_JCEM_2010.pdf |
| PubMed reference number | 20826583v1 |
| Alternate Webpage(s) | https://doi.org/10.1210/jc.2010-0860 |
| DOI | 10.1210/jc.2010-0860 |
| Journal | The Journal of clinical endocrinology and metabolism |
| Volume Number | 95 |
| Issue Number | 12 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Blood Glucose Diabetes Mellitus Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus, Non-Insulin-Dependent Genetic Polymorphism Glucose Metabolism Disorders Glucose tolerance test Hereditary Diseases Hyperglycemia IFNG gene Impaired glucose tolerance Nitroprusside Single Nucleotide Polymorphism Subgroup A Nepoviruses insulin secretion insulin, isophane |
| Content Type | Text |
| Resource Type | Article |
