Zinc‐finger BED domain‐containing 3 (Zbed3) is a novel secreted protein associated with insulin resistance in humans

Abstract

). Zinc-finger BED domain-containing 3 (Zbed3) is a novel secreted protein associated with insulin resistance in humans. J Intern Med 2014; 275: 522-533.Objectives. Genome-wide association studies (GWAS) have shown that Zbed3 is associated with T2DM. To date, no report has demonstrated a relationship between Zbed3 and insulin resistance in humans, however. The purpose of this study was to determine whether the Zbed3 protein is secreted and identify any associations between Zbed3 and insulin resistance in cross-sectional and interventional studies.Methods. We found that Zbed3 protein was secreted in an in vitro secretion study. Plasma Zbed3 levels were determined in an ELISA and were compared with various parameters related to insulin resistance in subjects with NGT, IGT and nT2DM. EHC was performed in healthy subjects. Real-time PCR and Western blotting were used to assess the mRNA and protein expression of Zbed3.Results. Zbed3 was detected in an analysis of in vitro secretion in both conditioned medium and lysates of HEK-293T cells transfected with an overexpressed vector. In a clinical study, there were significantly higher levels of circulating Zbed3 in IGT and nT2DM relative to NGT. Zbed3 levels were positively correlated with BMI, WHR, FAT%, blood pressure, FBG, TG, HbA1c, FIns and HOMA-IR and inversely correlated with HDL-C. Increasing levels of Zbed3 were independently associated with IGT and T2DM. Zbed3 mRNA and protein in muscle and fat were significantly elevated in both db/db mice and T2DM patients. Moreover, there was a concentration-dependent effect of glucose on Zbed3 release, whereas insulin exhibited an inhibitory effect on Zbed3 levels. Zbed3 suppressed insulin-induced IR and Akt phosphorylation.Conclusions. These results suggest that the Zbed3 protein may be a cytokine associated with insulin resistance in humans that is influenced by glucose and insulin levels.

Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread

“…In animals, proteins with BED domains were initially described in Drosophila, where they have DNA-binding activities (Aravind, 2000). BED proteins in animals have diverse molecular functions; for instance, the Zbed3 protein is a transcriptional regulator (Wang et al, 2013b) while Zbed6 is secreted to the membrane (Jia et al, 2014). To understand the role of BED domains in plant immunity, thorough investigation of ZBED and related BED proteins will be required.…”

Circulating C1q/TNF‐related protein isoform 15 is a marker for the presence of metabolic syndrome

“…Individuals with symptomatic heart failure, liver cirrhosis, hepatic and renal failure, long‐term steroid use, cancer, active infection, or other medical problems were excluded. Individuals were identified as having normal glucose tolerance, impaired glucose tolerance, or T2DM by World Health Organization 1998 diagnostic criteria . In the current cohort, all MetS individuals were newly diagnosed without any agents, diet control, or physical exercise for treatment.…”

“…In the current study, we examined serum CTRP15 concentrations in Organization 1998 diagnostic criteria. 16 In the current cohort, all MetS individuals were newly diagnosed without any agents, diet control, or physical exercise for treatment. The control subjects had normal blood glucose, no family history ofT2DM, and hypertension, no any clinical evidence of diseases, and were not using medications.…”

Krüppel-like factor 14 increases insulin sensitivity through activation of PI3K/Akt signal pathway

“…Although the precise mechanisms underlying the development and progression of T2DM have not been elucidated, it is thought that genetic factors play an important role in the pathogenesis of T2DM [2]. To date, many significant genome-wide common variants associations with the risk of T2DM have been described, mostly through genome-wide association (GWAS) analyses [3][4][5][6][7][8][9][10].Most of these risk variants were reported to contribute to β-cell dysfunction and/or metabolic disorder. These variants were either common with negligible effect or rare with a relatively greater effect [11] .…”