The role of PANDER and its interplay with IL-6 in the regulation of GLP-1 secretion

• Published in: Endocrine Connections Vol. 13; no. 11; pp. 1 - 12
• Main Authors: Li, Zeting, Pei, Ling, Xiao, Huangmeng, Chen, Nan, Lai, Fenghua, Yue, Shufang, Xu, Changliu, Li, Yanbing, Xiao, Haipeng, Cao, Xiaopei
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.11.2024; Bioscientifica
• Subjects: family with sequence similarity 3b; gestational diabetes mellitus; glucose-like peptide-1; interleukin-6; pancreatic-derived factor
• ISSN: 2049-3614; 2049-3614
• DOI: 10.1530/EC-23-0548

Glucose-like peptide-1 (GLP-1) is a vital hormone in the intestines that regulates glucose metabolism. Although pancreatic-derived factor (PANDER) overexpression is known to suppress GLP-1, the underlying mechanisms are unclear. Our study aims to uncover how PANDER influences GLP-1 synthesis and secretion. We established a PANDER overexpression model in STC-1 intestinal cells, confirming its inhibitory effect on GLP-1 secretion. This effect was reversed in PANDER-knockout cells. Additionally, a negative correlation between PANDER and GLP-1 was observed in patients with a history of gestational diabetes. Subsequently, through whole transcriptome gene sequencing in PANDER-overexpressed STC-1 cells, we discovered that the activation of IL-6 and its related STAT3 signaling pathway was significantly inhibited, and this finding was validated by Western blotting and quantitative reverse transcription PCR. Finally, rescue experiments confirmed that the IL-6-related STAT3/Akt/GSK3β/β-catenin signaling pathway mediates the negative regulatory effect of PANDER on GLP-1. Taken together, our data identify IL-6 as a bridge connecting PANDER and GLP-1 in the STC-1 cells, demonstrating potential therapeutic targets for diabetes treatment by targeting the PANDER–IL-6–GLP-1 axis.