The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from β cells

Fen Liu, Zixin Cai, Yan Yang, George Plasko, Piao Zhao, Xiangyue Wu, Cheng Tang, Dandan Li, Ting Li, Shanbiao Hu, Lei Song, Shaojie Yu, Ran Xu, Hairong Luo, Libin Fan, Ersong Wang, Zhen Xiao, Yujiao Ji, Rong Zeng, Rongxia LiJuli Bai, Zhiguang Zhou, Feng Liu, Jingjing Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic β cell failure is a hallmark of diabetes. However, the causes of β cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue-enriched secretory molecule, as a negative regulator of insulin secretion in β cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet-fed mice. Mechanistically, TN binds with high selectivity to β cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-β cell cross-talk that contributes to β cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

Original languageEnglish (US)
Article numbereabq1799
JournalScience Advances
Volume8
Issue number38
DOIs
StatePublished - Sep 23 2022

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from β cells'. Together they form a unique fingerprint.

Cite this