Deficiency of PRKD2 triggers hyperinsulinemia and metabolic disorders

Yao Xiao, Can Wang, Jia-Yu Chen, Fujian Lu, Jue Wang, Ning Hou, Xiaomin Hu, Fanxin Zeng, Dongwei Ma, Xueting Sun, Yi Ding, Yan Zhang, Wen Zheng, Yuli Liu, Haibao Shang, Wenzhen Zhu, Chensheng Han, Yulin Zhang, Kunfu Ouyang, Liangyi Chen, Ju Chen, Rui-Ping Xiao, Chuan-Yun Li () and Xiuqin Zhang ()
Additional contact information
Yao Xiao: Peking University
Can Wang: Peking University
Jia-Yu Chen: Peking University
Fujian Lu: Peking University
Jue Wang: Peking University
Ning Hou: Peking University
Xiaomin Hu: Peking University
Fanxin Zeng: Peking University
Dongwei Ma: Peking University
Xueting Sun: Peking University
Yi Ding: Peking University
Yan Zhang: Peking University
Wen Zheng: Peking University
Yuli Liu: Peking University
Haibao Shang: Peking University
Wenzhen Zhu: Peking University
Chensheng Han: Peking University
Yulin Zhang: Peking University
Kunfu Ouyang: Peking University Shenzhen Graduate School
Liangyi Chen: Peking University
Ju Chen: University of California San Diego School of Medicine
Rui-Ping Xiao: Peking University
Chuan-Yun Li: Peking University
Xiuqin Zhang: Peking University

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Hyperinsulinemia is the earliest symptom of insulin resistance (IR), but a causal relationship between the two remains to be established. Here we show that a protein kinase D2 (PRKD2) nonsense mutation (K410X) in two rhesus monkeys with extreme hyperinsulinemia along with IR and metabolic defects by using extreme phenotype sampling and deep sequencing analyses. This mutation reduces PRKD2 at both the mRNA and the protein levels. Taking advantage of a PRKD2-KO mouse model, we demonstrate that PRKD2 deletion triggers hyperinsulinemia which precedes to IR and metabolic disorders in the PRKD2 ablation mice. PRKD2 deficiency promotes β-cell insulin secretion by increasing the expression and activity of L-type Ca2+ channels and subsequently augmenting high glucose- and membrane depolarization-induced Ca2+ influx. Altogether, these results indicate that down-regulation of PRKD2 is involved in the pathogenesis of hyperinsulinemia which, in turn, results in IR and metabolic disorders.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-04352-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04352-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-04352-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().