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

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 s...

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Published in:Science advances 2022-09, Vol.8 (38), p.eabq1799-eabq1799
Main Authors: Liu, Fen, Cai, Zixin, Yang, Yan, Plasko, George, Zhao, Piao, Wu, Xiangyue, Tang, Cheng, Li, Dandan, Li, Ting, Hu, Shanbiao, Song, Lei, Yu, Shaojie, Xu, Ran, Luo, Hairong, Fan, Libin, Wang, Ersong, Xiao, Zhen, Ji, Yujiao, Zeng, Rong, Li, Rongxia, Bai, Juli, Zhou, Zhiguang, Liu, Feng, Zhang, Jingjing
Format: Article
Language:English
Subjects:
Biomedicine and Life Sciences
Health and Medicine
Life Sciences
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Summary: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 Ca 2+ 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. The adipocyte-enriched secretory molecule tetranectin aggravates type 2 diabetes by inhibiting insulin secretion in β cells.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abq1799