期刊
DIABETES OBESITY & METABOLISM
卷 23, 期 1, 页码 281-286出版社
WILEY
DOI: 10.1111/dom.14216
关键词
dipeptidyl peptidase‐ 4; DPP‐ 4; GLP‐ 1; GLP1R; glucagon‐ like peptide 1; sitagliptin
资金
- National Institutes of Health [HL125426, DK007061, GM007569, TR001879]
- Vanderbilt Clinical and Translational Science Awards [UL1 TR000445]
- American Heart Association [17SFRN33520059]
- [DK020593]
Genetic variation in the gene encoding the GLP-1 receptor may affect the metabolic response to DPP-4 inhibitors. The rs6923761 variant was associated with decreased postprandial glucose excursion in individuals with type 2 diabetes and hypertension. The study suggests a potential role of GLP1R rs6923761 genotype in modulating GLP-1 signaling in response to treatment.
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endogenous glucagon-like peptide-1 (GLP-1). We hypothesized that genetic variation in the gene encoding the GLP-1 receptor (GLP1R) could affect the metabolic response to DPP-4 inhibition. To evaluate the relationship between the GLP1R rs6923761 variant (G-to-A nucleic acid substitution) and metabolic responses, we performed mixed meal studies in individuals with type 2 diabetes mellitus and hypertension after 7-day treatment with placebo and the DPP-4 inhibitor sitagliptin. This analysis is a substudy of NCT02130687. The genotype frequency was 13:12:7 GG:GA:AA among individuals of European ancestry. Postprandial glucose excursion was significantly decreased in individuals carrying the rs6923761 variant (GA or AA) as compared with GG individuals during both placebo (P = 0.001) and sitagliptin treatment (P = 0.045), while intact GLP-1 levels were similar among the genotype groups. In contrast, sitagliptin lowered postprandial glucose to a greater degree in GG as compared with GA/AA individuals (P = 0.035). The relationship between GLP1R rs6923761 genotype and therapies that modulate GLP-1 signalling merits study in large populations.
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