Fig 2: Relation of PANDER, GLP-1, IL-6, and insulin of women with GDM history. GLP-1 levels (A), IL-6 levels (C), and insulin levels (G) of GDM patients between the four groups after being divided into four groups based on the quartile value of PANDER; Pearson correlation of PANDER with GLP-1 (B), IL-6 (D), and insulin (H) of women with GDM history; GLP-1 and IL-6 levels of GDM patients between the four groups after being divided into four groups based on the quartile value of GLP-1 (E); Pearson correlation of IL-6 with GLP-1 of women with GDM history (F). G1, 0–25th value; G2, 25–50th value; G3, 50–75th value; G4, 75–100th.

Fig 3: Relation between PANDER and IL-6 in GLP-1 secretion of STC-1 cells. Construction of PANDER-IL-6 double-knockdown STC-1 cells using the CRISPR–Cas9 system, validated by ELISA (A, B). Validation of PANDER-IL-6 double-knockdown in STC-1 cells was established by ELISA (C, D). After PANDER-IL-6 double-knockdown, STC-1 cells exhibited a decrease in GLP-1 secretion versus the PANDER knockdown group (ELISA, E). *P < 0.05, **P < 0.01, ***P < 0.001.

Fig 4: The inhibitory effect of PANDER on GLP-1 in STC-1 cells. Construction of PANDER-overexpressing STC-1 cells using the lentiviral overexpression method, validated by qPCR (A) and Western blot (B, C). Construction of PANDER-knockdown STC-1 cells using the CRISPR–Cas9 system, validated by qPCR (D) and Western blot (E, F). GCG gene expression (G), supernatant GLP-1 level (H), and GLP-1 protein expression (I, J) in the PANDER-overexpressing STC-1 cells. GCG gene expression (K), supernatant GLP-1 level (L), and GLP-1 protein expression (M, N) in the PANDER-knockdown STC-1 cells. The scale of the immunofluorescence image is 1 cm : 20 μm. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.001.

Fig 5: The mediated effect of IL-6 and the STAT3/Akt/GSK3β/β-catenin pathway in the inhibiting effect of PANDER on GLP-1. After PANDER overexpression, STC-1 cells exhibited a decrease in the phosphorylation of STAT3/Akt/GSK3β, and the expression of β-catenin (Western blot, A–E). The exogenous addition of IL-6 reversed the activation of the STAT3/Akt/GSK3β/β-catenin pathway (Western blot, F–J) and restored the expression of GLP-1 protein in the PANDER-overexpressing group (immunofluorescence, P, Q). In contrast, after PANDER knockdown, STC-1 cells exhibited an increase in the phosphorylation of STAT3/Akt/GSK3β, and the expression of β-catenin (Western blot, K–O). The exogenous addition of the STAT3-specific inhibitor AG490 inhibited the activation of the STAT3/Akt/GSK3β/β-catenin pathway (Western blot, K–O) and the expression of GLP-1 protein in the PANDER-knockdown group (immunofluorescence, R, S). The scale of the immunofluorescence image is 1 cm : 20μ m. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.001.