Year: 2018
Type: article
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 reducesPRKD2at both the mRNA and the protein levels. Taking advantage of aPRKD2-KOmouse model, we demonstrate thatPRKD2deletion triggers hyperinsulinemia which precedes to IR and metabolic disorders in thePRKD2ablation mice.PRKD2deficiency 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 ofPRKD2is involved in the pathogenesis of hyperinsulinemia which, in turn, results in IR and metabolic disorders.
Source: Nature Communications
Authors: 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, Xiuqin Zhang
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W2804103081