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

IF 2.6 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Endocrine Connections Pub Date : 2024-10-04 Print Date: 2024-10-01 DOI:10.1530/EC-23-0548

Zeting Li, Ling Pei, Huangmeng Xiao, Nan Chen, Fenghua Lai, Shufang Yue, Changliu Xu, Yanbing Li, Haipeng Xiao, Xiaopei Cao

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Abstract

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.

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PANDER 及其与 IL-6 在调节 GLP-1 分泌中的相互作用。

葡萄糖样肽-1（GLP-1）是肠道中调节葡萄糖代谢的一种重要激素。虽然已知胰腺衍生因子（PANDER）过表达会抑制 GLP-1，但其潜在机制尚不清楚。我们的研究旨在揭示 PANDER 如何影响 GLP-1 的合成和分泌。我们在 STC-1 肠细胞中建立了 PANDER 过表达模型，证实了它对 GLP-1 分泌的抑制作用。在 PANDER 基因敲除的细胞中，这种效应被逆转。此外，在有妊娠糖尿病史的患者中观察到 PANDER 与 GLP-1 之间存在负相关。随后，通过对高表达 PANDER 的 STC-1 细胞进行全转录组基因测序，我们发现 IL-6 及其相关的 STAT3 信号通路的激活受到了显著抑制，这一发现也得到了 WB 和 QPCR 的验证。最后，拯救实验证实，与 IL-6 相关的 STAT3/Akt/GSK3β/β-catenin 信号通路介导了 PANDER 对 GLP-1 的负向调节作用。综上所述，我们的数据发现，IL-6是连接STC-1细胞中PANDER和GLP-1的桥梁，通过靶向PANDER-IL-6-GLP-1轴，证明了糖尿病治疗的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine Connections Medicine-Internal Medicine

CiteScore

5.00

自引率

3.40%

发文量

361

审稿时长

6 weeks

期刊介绍： Endocrine Connections publishes original quality research and reviews in all areas of endocrinology, including papers that deal with non-classical tissues as source or targets of hormones and endocrine papers that have relevance to endocrine-related and intersecting disciplines and the wider biomedical community.