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

被引：4

作者：

Liu, Fen ^{[1
,2
]}

Cai, Zixin ^{[1
,2
]}

Yang, Yan ^{[1
]}

Plasko, George ^{[3
]}

Zhao, Piao ^{[4
]}

Wu, Xiangyue ^{[4
]}

Tang, Cheng ^{[4
]}

Li, Dandan ^{[1
,2
]}

Li, Ting ^{[5
]}

Hu, Shanbiao ^{[6
]}

Song, Lei ^{[6
]}

Yu, Shaojie ^{[6
]}

Xu, Ran ^{[7
]}

Luo, Hairong ^{[1
,2
]}

Fan, Libin ^{[1
,2
]}

Wang, Ersong ^{[8
]}

Xiao, Zhen ^{[4
]}

Ji, Yujiao ^{[1
,2
]}

Zeng, Rong ^{[9
]}

Li, Rongxia ^{[9
]}

Bai, Juli ^{[1
,2
,3
]}

Zhou, Zhiguang ^{[1
,2
]}

Liu, Feng ^{[1
,2
]}

Zhang, Jingjing ^{[1
,2
]}

机构：

[1] Cent South Univ, Metab Syndrome Res Ctr, Natl Clin Res Ctr Metab Dis, Key Lab Diabet Immunol,Minist Educ,Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[2] Cent South Univ, Dept Endocrinol & Metab, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[3] Univ Texas Hlth San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA

[4] Hunan Normal Univ, Coll Life Sci, Natl & Local Joint Engn Lab Anim Peptide Drug Dev, Changsha, Peoples R China

[5] Cent South Univ, Dept Liver Organ Transplantat, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[6] Cent South Univ, Dept Urol Organ Transplantat, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[7] Cent South Univ, Dept Urol, Xiangya Hosp 2, Changsha 410011, Hunan, Peoples R China

[8] Fudan Univ, Jinshan Hosp, Dept Neurosurg, Shanghai 201508, Peoples R China

[9] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai 200031, Peoples R China

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 38期

基金：

中国国家自然科学基金;

关键词：

BINDING-PROTEIN; REDOX REGULATION; ADIPOSE-TISSUE; PLASMINOGEN; CALCIUM; THIOREDOXIN; PATHWAY; GLUCOSE; MICE; PROLIFERATION;

D O I：

10.1126/sciadv.abq1799

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pancreatic beta cell failure is a hallmark of diabetes. However, the causes of beta 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 beta 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 beta cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-beta cell cross-talk that contributes to beta cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

引用

页数：18

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