English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Genetic polymorphisms in  TCF7L2  are the strongest common risk variants for type 2 diabetes mellitus (T2D). We and others have shown that genetic variation in  TCF7L2  and  WFS1  affect incretin-stimulated insulin secretion. A recent genome-wide association study discovered genetic variants associated with incretin levels. We hypothesized that these SNPs (single nucleotide polymorphisms) interact with the well-known  TCF7L2  variant rs7903146 on insulin secretion due to their incretin altering effect.   Methods:  In this retrospective analysis, we used data from the cross-sectional TUEF-cohort ( n  = 2929) and a hyperglycemic clamp study using additional GLP-1 infusion at the end of the clamp ( n  = 76). Insulin secretion was measured by evaluating OGTT-derived indexes of insulin secretion and insulin/C-peptide levels during clamp. We genotyped rs7903146 in  TCF7L2 , rs10010131 in  WFS1 , and six SNPs associated with GLP-1 and GIP levels.   Results:  One of the six incretin-associated SNPs, rs17681684 in  GLP2R , exhibited significant SNP x SNP interactions with rs7903146 in  TCF7L2  on insulin secretion ( p  = 0.0024) after correction for multiple testing. Three further SNP‘s showed nominally significant interactions ( p  < 0.05). In the hyperglycemic clamp study, rs7903146 in  TCF7L2  also interacted with rs17681684 on AUC C-peptide during the GLP-1 stimulation phase, thereby replicating the above finding.   Conclusion:  The findings exemplify the role of SNP x SNP interactions in the genetics of type 2 diabetes mellitus and corroborate the existence of clinically relevant differences in incretin sensitivity.

Gene x Gene Interactions Highlight the Role of Incretin Resistance for Insulin Secretion