The variation at rs2291725 affects the bioactivity of translated products. (A) GIP55G peptide is resistant to serum degradation. Treatments of GIP receptor-expressing HEK293T cells with GIP, GIP55G or GIP55S led to dose-dependent increases of cAMP production (top left panel). Receptor-activation activities of peptides were also analyzed following incubation with pooled normal human serum for 3, 6, or 12 h. Cells were treated with synthetic peptides for 12 h; the signaling is reported as total cAMP contents in cell lysates. Error bars, SEM of triplicate samples. Significant differences in cAMP production between GIP and GIP55G treatments at a given peptide concentration are indicated by asterisks (P < 0.01). In the control group, cells were treated with an aliquot of human serum without a synthetic peptide. Similar results were observed in three separate experiments. (B) Comparison of the slopes of EC50 trend lines for GIP, GIP55G, and GIP55S after treatments with pooled human serum for the indicated time-spans. The slope of the GIP55G group is significantly different from that of the GIP group (*P = 0.0023).
