| The impact of genetic variation in the G6PC2 gene on insulin secretion depends on glycemia. | |
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MedLine Citation:
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PMID: 20826583 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Martin Heni; Caroline Ketterer; Leen M 't Hart; Felicia Ranta; Timon W van Haeften; Elisabeth M Eekhoff; Jacqueline M Dekker; Dorret I Boomsma; Giel Nijpels; Mark H Kramer; Michaela Diamant; Annemarie M Simonis-Bik; Robert J Heine; Eco J de Geus; Silke A Schäfer; Fausto Machicao; Susanne Ullrich; Claus Thamer; Norbert Stefan; Harald Staiger; Hans-Ulrich Häring; Andreas Fritsche |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-08 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-01-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E479-84 Citation Subset: AIM; IM |
Affiliation:
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Department of Internal Medicine, Eberhard Karls University Tübingen, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Blood Glucose / metabolism* Carrier State Cross-Sectional Studies Diabetes Mellitus, Type 2 / genetics Fasting Female Gene Frequency Genetic Variation* Genome-Wide Association Study Genotype Glucose Clamp Technique Glucose Intolerance / genetics Glucose Tolerance Test Glucose-6-Phosphatase / genetics* Humans Insulin / secretion* Insulin-Secreting Cells / physiology Male Middle Aged Polymorphism, Single Nucleotide* |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 11061-68-0/Insulin; EC 3.1.3.9/Glucose-6-Phosphatase; EC 3.1.3.9./G6PC2 protein, human |
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