Authors
Sheng-Zhong Han, Shuang-Yan Chang, Zhaobo Luo, Ke Sun, Biaohu Quan, Yanqiu Lv, Zhouyan Li, Xinyue Liu, Sitong Lv, Meifu Xuan, Xiaoyufan Xu, Xue Fang, Hang Chang, Rihuan Zhang, Xi-Jun Yin, Lin-Hu Quan, Jin-Dan Kang
Published in
Advanced science (Weinheim, Baden-Wurttemberg, Germany). Pages e78302. Oct 14, 2026. Epub Oct 14, 2026.
Abstract
Intestinal glucagon-like peptide-1 (GLP-1) is secreted by intestinal L cells in a glucose-dependent manner. The localization and surface abundance of glucose-sensing proteins on the cell membrane affect the response to glucose, but the regulatory mechanism remains poorly understood. Here, we show that S-palmitoylation is required for stable plasma membrane enrichment of SGLT1 and for SGLT1-mediated GLP-1 secretion. Notably, myostatin (MSTN) was identified as a key upstream regulator of this modification. Intestinal MSTN deficiency markedly enhanced SGLT1 palmitoylation, increased its plasma membrane abundance, and thereby promoted glucose-stimulated GLP-1 secretion. Importantly, simvastatin induced intestinal MSTN upregulation and impaired glucose homeostasis, whereas MSTN deficiency largely alleviated these effects. Mechanistically, MSTN regulated the expression of the palmitoyl acyltransferase ZDHHC20, which catalyzed SGLT1 S-palmitoylation at Cys301. Blocking SGLT1 palmitoylation attenuated SGLT1 membrane enrichment and markedly suppressed the induction of GLP-1 secretion caused by MSTN deficiency. Collectively, our research results have revealed a new mechanism by which MSTN regulates intestinal endocrine function and S-palmitoylation modification promotes GLP-1 secretion, providing potential targets for regulating endogenous GLP-1 secretion in the intestine and treating metabolic diseases related to glucose imbalance.
PMID:
42876031
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.
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