The Prevalent Glu23Lys Polymorphism in the Potassium Inward Rectifier 6.2 (KIR6.2) Gene Is Associated With Impaired Glucagon Suppression in Response to Hyperglycemia
| Autor: | Hans U. Häring, Melanie Weisser, Martin Holzwarth, Andreas Fritsche, E. Maerker, Anna Teigeler, Fausto Machicao, Otto Tschritter, Michael Stumvoll |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Glutamic Acid Type 2 diabetes Peptide hormone Biology Carbohydrate metabolism Glucagon Islets of Langerhans Insulin resistance Gene Frequency Internal medicine Insulin Secretion Internal Medicine medicine Humans Insulin Potassium Channels Inwardly Rectifying Alleles Polymorphism Genetic Lysine Glucagon secretion Kir6.2 medicine.disease Endocrinology Hyperglycemia Female |
| Zdroj: | Diabetes. 51:2854-2860 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Genetic factors play an important role in the pathogenesis of type 2 diabetes. The relevance to type 2 diabetes of the common polymorphism Glu23Lys in the potassium inward rectifier 6.2 (KIR6.2) gene is still controversial. The aim of this study was to assess whether this polymorphism influences beta-cell function, alpha-cell function, or insulin action. We therefore studied 298 nondiabetic subjects using an oral glucose tolerance test (OGTT) and 75 nondiabetic subjects using a hyperglycemic clamp (10 mmol/l) with additional glucagon-like peptide (GLP)-1 and arginine stimulation. The prevalence of the Lys allele was approximately 37%, and the Lys allele was associated with higher incremental plasma glucose during the OGTT (P = 0.03, ANOVA). Neither first- nor second-phase glucose-stimulated C-peptide secretion was affected by the presence of the polymorphism; nor were maximal glucose-, GLP-1-, or arginine-induced C-peptide secretion rates; nor was insulin sensitivity (all P0.7). However, the relative decrease in plasma glucagon concentrations during the 10 min after the glucose challenge was reduced in carriers of the Lys allele (10 +/- 3% decrease from baseline in Lys/Lys, 18 +/- 2% in Glu/Lys, and 20 +/- 2% in Glu/Glu; P = 0.01, ANOVA). In conclusion, our findings suggest that the common Glu23Lys polymorphism in KIR6.2 is not necessarily associated with beta-cell dysfunction or insulin resistance but with diminished suppression of glucagon secretion in response to hyperglycemia. Our findings thus confirm its functional relevance for glucose metabolism in humans. |
| Databáze: | OpenAIRE |
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