Secretagogin Is Highly Expressed in Enteroendocrine K Cells and Plays a Critical Role in Nutrient-Induced GIP Secretion

促泌素在肠内分泌 K 细胞中高度表达,在营养诱导的 GIP 分泌中起关键作用

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作者:Xinyu Liu, Xuan Liu, Yuanyuan Hu, Xin Wang, Xin Yang, Bin Yan, Yiting Zhou, Lingzhi Zhou, Gang Fan, Jing Yang

Conclusion

Collectively, these findings demonstrate that SCGN is a key regulator of nutrient-induced GIP secretion.

Methods

We collected duodenal tissues from both humans and mice to observe the colocalization of SCGN and GIP in EECs. Additionally, we utilized human cohorts and gene-edited mouse models to investigate the effect of SCGN on GIP secretion. Our study included 128 subjects, comprising 64 individuals diagnosed with newly onset diabetes and 64 age- and sex-matched nondiabetic healthy controls. At the animal level, we employed leptin receptor-deficient (db/db) mice and Scgn knockout mice for our investigations.

Objective

Our study aims to explore the role of an EEC-enriched protein, Secretagogin (SCGN), in the regulation of GIP secretion.

Results

Our findings indicate that SCGN is abundantly expressed in GIP-producing K cells within the intestinal epithelium of both humans and mice. We observed a positive correlation between SCGN and GIP levels in postprandial states among patients with T2DM, db/db mice, and their healthy controls. Notably, Scgn knockout mice exhibited decreased GIP and insulin secretion. However, SCGN deficiency did not affect K-cell number, GIP mRNA expression, or intestinal morphology.

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