Authors: F. Liu, Z. Cai, Y. Yang, G. Plasko, P. Zhao, X. Wu, C. Tang, D. Li, T. Li, S. Hu, L. Song, S. Yu, R. Xu, H. Luo, L. Fan, E. Wang, Z. Xiao, Y. Ji, R. Zeng, R. Li, J. Bai, Z. Zhou, F. Liu, J. Zhang
Publication: Science Advances
Date: September, 2022
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.