C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1

Xin, Ya; Zhang, Dongming; Fu, Yanqin; Wang, Chongxian; Li, Qingju; Tian, Chenguang; Suhe, Zhang; Lyu, Xiaodong

doi:10.1507/endocrj.ej17-0128

Cited by 21 publications

(19 citation statements)

References 23 publications

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“…Previous studies suggested that members of CTRP superfamily, including adiponectin, CTRP1, CTRP3, CTRP5, CTRP6, and CTRP15, are involved in the regulation of several metabolic and inflammatory pathways. For instance, CTRP1 forms an oligo‐heterotrimer with CTRP6, and is known to enhance glucose uptake and insulin sensitivity . Elevated levels of CTRP1 have been associated with BMI, T2DM, nonalcoholic fatty liver disease (NAFLD), congestive heart failure (CHF), and chronic kidney disease progression .…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor‐α‐related protein‐6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf‐PCOS] and PCOS‐RPL). This case–control study included 120 PCOS patients (60 inf‐PCOS and 60 PCOS‐RPL) and 60 healthy controls. Serum high‐sensitivity C‐reactive protein (hs‐CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf‐PCOS and PCOS‐RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs‐CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs‐CRP in PCOS group and inf‐PCOS subgroup, but not PCOS‐RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

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Section: Discussionmentioning

confidence: 99%

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

et al. 2020

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“…The C1QTNF family has a highly conserved c-terminal complementary C1q domain consisting of 16 CTRP members, including C1QTNF 1-9,9b, 10-15 [13]. All C1QTNF members are secreted proteins that are widely expressed in a variety of tissues and cell types and are involved in a variety of biological processes, including host defense, in ammation, apoptosis, autoimmunity, cell differentiation, organogenesis, hibernation, and insulin-resistant obesity [14][15][16][17][18][19]. C1QTNF6, as a member of C1QTNF family, was demonstrated to be associated with carcinogenesis in digestive cancers, however, the biological functions in bladder cancer still required investigating.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of C1QTNF6 Predicts a Poor Prognosis in Bladder Cancer

Zhu

Tong

Gao

et al. 2020

Preprint

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Background: Bladder cancer is one of the most common urinary cancer. This study aimed to provide promising molecular biomarkers for bladder cancer by investigating the correlations between C1QTNF6 expressions and clinical characteristics as well as prognosis in patients with bladder cancer.Methods: C1QTNF6 RNA sequencing profiles of bladder cancer patients were collected to evaluate different expressions between normal bladder mucosa and bladder cancer from TCGA database and GEO database. The associations between C1QTNF6 expression and clinical characteristics as well as prognosis were evaluated by two independent cohorts. The cell expression of C1QTNF6 expression between normal bladder cell and bladder cancer cells were tested in western blot and PCR, and the underlying molecular mechanism was investigated.Results: RNA levels of C1QTNF6 were found to be differentially expressed in two independent public cohorts including TCGA database and GSE13507 from GEO database. The protein and RNA expressions C1QTNF6 in bladder cell lines were both significantly elevated than normal bladder cell line. High C1QTNF6 expressions were found in advanced T status, M status, pathological grade, AJCC stage compared with low C1QTNF6 expression group. The underlying mechanism may be explained by cell migration and invasion assays that bladder cancer cells 5637 and T24 were significantly reduced migration and invasion ability with the knock-down C1QTNF6 expressions. The low RNA expression group of C1QTNF6 demonstrated OS advantage over high-expression group in both TCGA and GSE13507 cohorts. Besides, protein expressions in tissues were further validated in HPA database and TMA. Survival analysis also indicated that the high expression of C1QTNF6 indicated unfavorable OS compared with low expressions group.Conclusions: High expression of C1QTNF6 predicted poor prognosis for bladder cancer patients, and the underlying mechanism is associated with cancer cell migration and invasion ability.

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“…25 It is reported that GLP-1 receptor agonist, the novel antidiabetic drug (Ex-4), can improve lipid deposition in hepatocytes. 26,27 Studies indicated that activation of the central nerve system GLP-1 receptor improves T2DM via glucose metabolism dependent inhibition of central nerve system AMPK. 28 AMPK activation accelerate fatty acid oxidation and glucose uptake, suppresses triglycerides production in skeletal muscle，which is necessary for the body to maintain the balance of blood glucose.…”

Section: Discussionmentioning

confidence: 99%

Exendin-4 improves glucose metabolism in insulin-resistant cells by upregulating the phosphorylative AMPK

Li¹,

Gong²,

Qu³

et al. 2019

JAH

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Glucagon-like peptide-1 (GLP-1) is a peptide with multiple functions in regulating blood glucose with the mechnism still not throughly understand. AMP-activated protein kinase (AMPK) plays an important role in glucose and energy homeostasis, especially in type 2 diabetes mellitus (T2DM) pathophysiology. This study explores GLP-1 analogue exendin-4 (Ex-4) regulating glucose balance by activating AMPK and regulation gluconeogenesis in insulin-resistant cell model (IR/ HepG2). IR/HepG2 cells were treated with Ex-4, AMPK activator or Ex-4 pretreated with AMPK inhibitor Compound C. The change of cell morphology, glucose consumption and lipid content in IR/HepG2 cells were examined. The expression of AMPK and p-AMPK in IR/HepG2 treated by Ex-4 were determined by Western blot and immunochemisthistology (IHC) assay. Key enzymes of glucose metabolism, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) in IR/HepG2 cells treated by Ex-4 were detected by Western blot, immunohistochemistry and qRT-PCR. The results showed that Ex-4 treatment increased the expression of p-AMPK and reduced the expression of G-6-Pase and PEPCK in IR/HepG2 cells. Pretreatment with AMPK inhibitor Compound C counteracts the effect of Ex-4. These findings suggest that Ex-4 fulfilled it glucose regulation effect by phosphorylation of AMPK and decreased the expression of enzymes involving gluconeogenesis.

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C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1

Cited by 21 publications

References 23 publications

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Circulating levels of C1q/TNF‐α‐related protein 6 (CTRP6) in polycystic ovary syndrome

Overexpression of C1QTNF6 Predicts a Poor Prognosis in Bladder Cancer

Exendin-4 improves glucose metabolism in insulin-resistant cells by upregulating the phosphorylative AMPK

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