Skip to main content

Advertisement

SpringerLink
Log in

C1q/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population

  • Original Article
  • Published:
Acta Diabetologica Aims and scope Submit manuscript

Abstract

Aims

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a novel adipokine and has emerged as an important mediator for lipid and glucose metabolism. However, to date, the relationship between CTRP6 and T2DM in humans has not been demonstrated. Our objective is to investigate the association of circulating CTRP6 with T2DM in a cross-sectional study.

Methods

118 patients with newly diagnosed T2DM, 98 subjects with impaired glucose tolerant (IGT) and 132 healthy subjects were recruited for this study. OGTT were performed in 48 healthy individuals to investigate the association of CTRP6 with glucose, insulin and other adipokines. Circulating CTRP6, TNF-α and Adipoq were measured by ELISA.

Results

IGT and T2DM individuals had higher serum CTRP6 levels than healthy controls (406.2 ± 136.6 and 539.1 ± 169.7 vs. 354.3 ± 117.2 ng/mL; both P < 0.01), whereas serum CTRP6 concentrations were further increased in T2DM patients compared with IGT individuals (P < 0.01). Serum CTRP6 levels were found to be related positively to BMI, WHR, FAT%, TC, TG, HbA1c, FBG, 2 h-OGTT, fasting insulin (FIns), 2 h-Ins, HOMA-IR and TNF-α, and negatively with HDL-C and Adipoq in all individuals (P < 0.05 or P < 0.01). Multivariate logistic regression analysis demonstrated that CTRP6 was correlated with both IGT and T2DM. After an oral glucose challenge, serum CTRP6 concentrations exhibited a similar change with blood glucose, insulin, TNF-α and Adipoq.

Conclusions

CTRP6 may be a metabolism- and nutrition-related adipokine and may be related to insulin resistance and T2DM.

Trial registrations

Clinical Trial Registration Number: ChiCTR-OCC-11001422. Registration name: Plasma cytokines and endothelial function in type 2 diabetes

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

CTRP6:

C1q/tumor necrosis factor-related protein-6

T2DM:

Type 2 diabetes mellitus

IGT:

Impaired glucose tolerant

NGT:

Normal subjects

OGTT:

Oral glucose tolerance tests

BMI:

Body mass index

WHR:

Waist-to-hip ratio

FAT%:

The percentage of body fat

HDL-C:

High-density lipoprotein cholesterol

TC:

Total cholesterol

TG:

Triglyceride

FBG:

Fasting blood glucose

2-h OGTT:

2-h blood glucose after glucose overload

FIns:

Fasting insulin

2-hIns:

2-h plasma insulin after glucose overload

HOMA-IR:

Homeostasis model assessment of insulin resistance

Adipoq:

Adiponectin

TNF-α:

Tumor necrosis factor-α

AUCglucose :

The area under the curve for insulin

References

  1. Luo L, Liu M (2016) Adipose tissue in control of metabolism. J Endocrinol 231(3):R77–R99

    Article  CAS  Google Scholar 

  2. Liao WL, Lee WJ, Chen CC et al (2017) Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes. Oncotarge 8(11):18050–18058

    Article  Google Scholar 

  3. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93(1):64–73

    Article  Google Scholar 

  4. Maury E, Brichard SM (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314(1):1–16

    Article  CAS  Google Scholar 

  5. Polyzos SA, Kountouras J, Mantzoros CS (2016) Adipokines in nonalcoholic fatty liver disease. Metabolism 65(8):1062–1079

    Article  CAS  Google Scholar 

  6. Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL et al (2017) Role of adipokines in cardiovascular disease. Circ J 81(7):920–928

    Article  CAS  Google Scholar 

  7. Wong GW, Wang J, Hug C, Tsao TS, Lodish HF (2004) A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci USA 101(28):10302–103027. https://doi.org/10.1073/pnas.0403760101

    Article  CAS  PubMed  Google Scholar 

  8. Wong GW, Krawczyk SA, Kitidis-Mitrokostas C, Revett T, Gimeno R, Lodish HF (2008) Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose-tissue-selective expression patterns, regulation by PPAR-γagonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J 416(2):161–177

    Article  CAS  Google Scholar 

  9. Seldin MM, Tan SY, Wong GW (2014) Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord 15(2):111–123

    Article  CAS  Google Scholar 

  10. Zheng Q, Yuan Y, Yi W et al (2011) C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway. Arterioscler Thromb Vasc Biol 31(11):2616–2623

    Article  CAS  Google Scholar 

  11. Lei H, Wu D, Wang JY et al (2015) C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation. Basic Res Cardiol 110(4):35

    Article  Google Scholar 

  12. Chi L, Hu X, Zhang W et al (2017) Adipokine CTRP6 improves PPARγ activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats. Biochem Biophys Res Commun 482(4):727–734

    Article  CAS  Google Scholar 

  13. Wu W, Sun Y, Zhao C et al (2016) Lipogenesis in myoblasts and its regulation of CTRP6 by AdipoR1/Erk/PPARγ signaling pathway. Acta Biochim Biophys Sin (Shanghai) 48(6):509–519

    Article  CAS  Google Scholar 

  14. Wu W, Zhang J, Zhao C, Sun Y, Pang W, Yang G (2017) CTRP6 regulates porcine adipocyte proliferation and differentiation by the AdipoR1/MAPK signaling pathway. J Agric Food Chem 65(27):5512–5522

    Article  CAS  Google Scholar 

  15. Wu WJ, Mo DL, Zhao CZ et al (2015) Knockdown of CTRP6 inhibits adipogenesis via lipogenic marker genes and Erk1/2 signalling pathway. Cell Biol Int 39(5):554–562

    Article  CAS  Google Scholar 

  16. Fan RH, Zhu XM, Sun YW, Peng HZ, Wu HL, Gao WJ (2016) CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts. Biochem Biophys Res Commun 475(4):356–360

    Article  CAS  Google Scholar 

  17. Murayama MA, Kakuta S, Inoue A et al (2015) CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis. Nat Commun 6:8483

    Article  CAS  Google Scholar 

  18. Cooper JD, Smyth DJ, Smiles AM et al (2008) Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet 40(12):1399–1401

    Article  CAS  Google Scholar 

  19. Lei X, Seldin MM, Little HC, Choy N, Klonisch T, Wong GW (2017) C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance. J Biol Chem 292(36):14836–14850

    Article  CAS  Google Scholar 

  20. Lee W, Kim MJ, Park EJ, Choi YJ, Park SY (2010) C1qTNF-related protein-6 mediates fatty acid oxidation via the activation of the AMP-activated protein kinase. FEBS Lett 584(5):968–972

    Article  CAS  Google Scholar 

  21. American Diabetes A (2011) Diagnosis and classification of diabetes mellitus. Diabetes Care 34(Suppl 1):S62–S69

    Article  Google Scholar 

  22. Li K, Xu X, Hu W et al (2014) Glypican-4 is increased in human subjects with impaired glucose tolerance and decreased in patients with newly diagnosed type 2 diabetes. Acta Diabetol 51(6):981–990

    Article  CAS  Google Scholar 

  23. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419

    Article  CAS  Google Scholar 

  24. Li L, Miao Z, Liu R, Yang M, Liu H, Yang G (2011) 11 Liraglutide prevents hypoadiponectinemia-induced insulin resistance and alterations of gene expression involved in glucose and lipid metabolism. Mol Med 17(11–12):1168–1178

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14(6):561–566

    Article  CAS  Google Scholar 

  26. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Investig 116(7):1784–1792

    Article  CAS  Google Scholar 

  27. Yang M, Liu R, Li S et al (2013) Zinc-α2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: cross-sectional and interventional studies in normal subjects, insulin-resistant subjects, and subjects with newly diagnosed diabetes. Diabetes Care 36(5):1074–1082

    Article  CAS  Google Scholar 

  28. Hu W, Li L, Yang M et al (2013) Circulating Sfrp5 is a signature of obesity-related metabolic disorders and is regulated by glucose and liraglutide in humans. J Clin Endocrinol Metab 98(1):290–298

    Article  CAS  Google Scholar 

  29. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97

    Article  CAS  Google Scholar 

  30. Kim MJ, Lee W, Park EJ, Park SY (2010) C1qTNF-related protein-6 increases the expression of interleukin-10 in macrophages. Mol Cells 30(1):59–64

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant 2017MSXM20 and 2016MSXM083 from the Science and Technology key Program of Health Bureau of Chongqing, China.

Author information

Author notes

  1. Miao Wang and Xuejiao Tang contributed equally to this project.

Authors and Affiliations

  1. Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    Miao Wang, Xuejiao Tang, Dongfang Liu, Xili Zhao & Gangyi Yang

  2. Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China

    Ling Li

  3. Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA

    Hua Liu

  4. Department of Endocrinology, Xinqiao Hospital, Third Military Medical University, Chongqing, China

    Hongting Zheng

  5. Chongqing Emergency Medical Center, Chongqing, China

    Wuquan Deng

  6. Department of Endocrinology, Chongqing Shizhu County People’s Hospital, Chongqing, China

    Xili Zhao

Authors
  1. Miao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xuejiao Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongfang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongting Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wuquan Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xili Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gangyi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GY and XZ designed this research (included project conception, development of overall research plan); XT, MW and WD supervised the studies, contributed to the discussion, and revised/edited the article. DL and HL collected the data and conducted the research; HZ provided essential reagents; LL, XZ interpreted the data and drafted the article; GY had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xili Zhao or Gangyi Yang.

Ethics declarations

Conflict of interest

The authors declare that there is no duality of interest associated with this manuscript. The authors declare no conflict of interest.

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Managed by Massimo Porta.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, M., Tang, X., Li, L. et al. C1q/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population. Acta Diabetol 55, 1221–1229 (2018). https://doi.org/10.1007/s00592-018-1203-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00592-018-1203-2

Keywords

Search

Navigation