CILP-2 is a novel secreted protein and associated with insulin resistance
CILP-2 is a novel secreted protein and associated with insulin resistance
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DOI：
10.1093/jmcb/mjz016
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发表时间：
2019
影响因子：
5.5
通讯作者：
Gangyi Yang
中科院分区：
文献类型：
--
作者：
Tong Wu;Qin Zhang;Shaobo Wu;Wenjing Hu;Tingting Zhou;Ke Li;Dongfang Liu;Harvest F Gu;Hongting Zheng;Zhiming Zhu;Ling Li;Gangyi Yang
Genetic association studies have implicated that cartilage intermediate layer protein 2 (CILP-2) confers the risk susceptibility for type 2 diabetes (T2DM). However, it is still unknown whether CILP-2 is involved in the regulation of glucose homeostasis and insulin resistance (IR). In the current study, we initially observed that CILP-2 as a secreted protein was detected in both conditioned medium and lysates of cells transfected with an overexpressed vector. We then found that circulating CILP-2 levels had a progressive increase from normal to IGT (a pre-diabetic status) and then to diabetes, which was correlated positively with WHR, triglyceride, FBG, 2-h blood glucose after glucose overload (2h-BG), HbA1c, FIns, 2h-Ins, and HOMA-IR but negatively with HDLC. CILP-2 expression was increased in the liver and muscle but decreased in adipose tissues of obese mice or T2DM patients..Furthermore, we demonstrated that CILP-2 circulating levels were affected by OGTT and Exenatide. CILP-2 overexpression resulted in impaired glucose tolerance and hepatic IR in vivo, and increased PEPCK expression whereas suppressed phosphorylation of InsR and Akt in vitro. Based on these findings, we have identified a direct interaction between CILP-2 and PEPCK and suggested that CILP-2 plays an important role in the regulation of hepatic glucose production.
