Single Nucleotide Polymorphisms of theMelanocortin-3 ReceptorGene Are Associated with Substrate Oxidation and First-Phase Insulin Secretion in Offspring of Type 2 Diabetic Subjects
| Autor: | Urpu Salmenniemi, Teemu Kuulasmaa, Jarno Rutanen, Markku Laakso, Sakari Kainulainen, Eija Ruotsalainen, Jussi Pihlajamäki, Markku Vänttinen |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty Offspring Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Type 2 diabetes Fatty Acids Nonesterified Biology Polymorphism Single Nucleotide Biochemistry Endocrinology Gene Frequency Melanocortin receptor Lipid oxidation Internal medicine Insulin Secretion medicine Humans Insulin Glucose tolerance test medicine.diagnostic_test Biochemistry (medical) Lipid Metabolism medicine.disease Melanocortin 3 receptor Diabetes Mellitus Type 2 Glucose Clamp Technique Adult Children Female Melanocortin Oxidation-Reduction Receptor Melanocortin Type 3 |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 92:1112-1117 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2006-1201 |
| Popis: | The melanocortin-3 receptor (MC3R) is a part of the melanocortin system that regulates appetite and energy metabolism. The Thr/Thr 6 and Val/Val81 [corrected] polymorphisms of the MC3R gene have been previously associated with high insulin levels and obesity in children.The objective was to determine whether single nucleotide polymorphisms (SNPs) of MC3R are associated with glucose, lipid, and energy metabolism.We screened the Lys/Thr6 and Ile/Val81 mutations and six noncoding SNPs of MC3R in a cross-sectional study of 216 middle-aged nondiabetic Finnish subjects who were offspring of type 2 diabetic patients.Insulin secretion was evaluated by an iv glucose tolerance test, and insulin sensitivity and energy metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry.Carriers of the Lys 6 and Ile 81 [corrected] alleles had significantly lower rates of lipid oxidation [0.85 +/- 0.38 vs. 1.00 +/- 0.43 mg/kg of lean body mass (LBM)/min; P = 0.022, adjusted for sex, body mass index, age, and family relationship] and higher rates of glucose oxidation in the fasting state (11.28 +/- 4.64 vs. 9.71 +/- 4.53 micromol/kg of LBM/min; P = 0.031) than subjects with the Thr/Thr 6 and Val/Val 81 [corrected] genotypes. They had lower rates of lipid oxidation during the hyperinsulinemic clamp (0.32 +/- 0.41 vs. 0.44 +/- 0.34 mg/kg of LBM/min; P = 0.021) and higher insulin levels in an iv glucose tolerance test (insulin under the curve during the first 10 min, 3220 +/- 1765 vs. 2454 +/- 1538 pmol/liter.min; P = 0.025) compared to subjects with the common genotypes.Our results suggest that SNPs of MC3R may regulate substrate oxidation and first-phase insulin secretion. |
| Databáze: | OpenAIRE |
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