Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
February-2015 Volume 9 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2015 Volume 9 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus

  • Authors:
    • Ren Wang
    • Lihua Dai
    • Jinjin Chen
  • View Affiliations / Copyright

    Affiliations: Department of Ultrasonography, Shanghai Sixth People's Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China, Department of Emergency, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, Department of Child Health Care, Shanghai Children's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200040, P.R. China
  • Pages: 446-450
    |
    Published online on: December 1, 2014
       https://doi.org/10.3892/etm.2014.2096
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

In the present study, a novel antagonist of the peroxisome proliferator‑activated receptor‑γ (PPARγ) was screened and identified, and a cell‑based evaluation of the biological activity of this PPARγ antagonist was conducted. The aim of the study was to produce results that may provide a foundation for the development of a novel compound in the treatment of type 2 diabetes mellitus. Since obesity is the main cause of insulin resistance and type 2 diabetes, identifying a new reagent that is able to inhibit adipocyte differentiation and lipid accumulation is a feasible method of developing novel anti-diabetes drugs. The PPARγ antagonist was screened using a mammalian one‑hybrid system and transcriptional activation. The effects of the compound on adipocyte differentiation were investigated by staining the preadipocytes with Oil Red O. In addition, the effects of the compound on the expression levels of genes associated with lipid metabolism were detected using quantitative polymerase chain reaction on differentiated mature 3T3‑L1 adipocytes. As a PPARγ antagonist, N-((1H-benzo[d]imidazol-2-yl)methyl) aniline (Compound Q) was shown to depress the transcriptional activity and coactivator recruitment of PPARγ, as well as preadipocyte differentiation, in a concentration‑dependent manner. The compound was also shown to decrease the expression levels of genes associated with PPARγ‑regulated lipid metabolism. In conclusion, the compound screening platform was demonstrated to be valid, and the present study identified a novel PPARγ antagonist that was shown to effectively reduce the rate of adipocyte differentiation and the expression of genes associated with lipid metabolism.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Samuel VT and Shulman GI: Mechanisms for insulin resistance: common threads and missing links. Cell. 148:852–871. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Kahn SE, Hull RL and Utzschneider KM: Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 444:840–846. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Kumar PR, Bhansali A, Ravikiran M, et al: Utility of glycated hemoglobin in diagnosing type 2 diabetes mellitus: a community-based study. J Clin Endocrinol Metab. 95:2832–2835. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Halperin F and Goldfine AB: Metabolic surgery for type 2 diabetes: efficacy and risks. Curr Opin Endocrinol Diabetes Obes. 20:98–105. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Houseknecht KL, Cole BM and Steele PJ: Peroxisome proliferator-activated receptor gamma (PPAR gamma) and its ligands: a review. Domest Anim Endocrinol. 22:1–23. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Bajaj M, Suraamornkul S, Hardies LJ, Glass L, Musi N and DeFronzo RA: Effects of peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus. Diabetologia. 50:1723–1731. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Sharma AM and Staels B: Review: Peroxisome proliferator-activated receptor gamma and adipose tissue - understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab. 92:386–395. 2007. View Article : Google Scholar

8 

Shearer BG and Billin AN: The next generation of PPAR drugs: do we have the tools to find them? Biochim Biophys Acta. 1771:1082–1093. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Clement K, Hercberg S, Passinge B, et al: The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes. Int J Obes Relat Metab Disord. 24:391–393. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Kadowaki T: PPAR gamma agonist and antagonist. Nihon Yakurigaku Zasshi. 118:321–326. 2001.(In Japanese). View Article : Google Scholar : PubMed/NCBI

11 

Zinman B: PPAR gamma agonists in type 2 diabetes: how far have we come in ‘preventing the inevitable’? A review of the metabolic effects of rosiglitazone. Diabetes Obes Metab. 3(Suppl 1): S34–S43. 2001. View Article : Google Scholar

12 

Wojtowicz AK, Szychowski KA and Kajta M: PPAR-γ agonist GW1929 but not antagonist GW9662 reduces TBBPA-induced neurotoxicity in primary neocortical cells. Neurotox Res. 25:311–322. 2014. View Article : Google Scholar

13 

de Boer RA, Martens FM, Kuipers I, Boomsma F and Visseren FL: The effects of the PPAR-gamma agonist pioglitazone on plasma concentrations of circulating vasoactive factors in type II diabetes mellitus. J Hum Hypertens. 24:74–76. 2010. View Article : Google Scholar

14 

Chawla A, Schwarz EJ, Dimaculangan DD and Lazar MA: Peroxisome proliferator-activated receptor (PPAR) gamma: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology. 135:798–800. 1994.PubMed/NCBI

15 

Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W and Qin Y: Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun. 348:571–578. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Sheu W, Jeng CY, Fuh M, Chen YD and Reaven GM: Resistance to insulin-mediated glucose disposal in patients with noninsulin-dependent diabetes mellitus in the absence of obesity or microalbuminuria - a Clinical Research Center study. J Clin Endocrinol Metab. 81:1156–1159. 1996.PubMed/NCBI

17 

Chatterjee PK: Hepatic inflammation and insulin resistance in pre-diabetes - further evidence for the beneficial actions of PPAR-gamma agonists and a role for SOCS-3 modulation. Br J Pharmacol. 160:1889–1891. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Khan A, Safdar M, Ali Khan MM, Khattak KN and Anderson RA: Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care. 26:3215–3218. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Bøg-Hansen E, Lindblad U, Rånstam J, Melander A and Rastam L: Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension: Skaraborg Hypertension and Diabetes Project. Diabetes Obes Metab. 3:25–31. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Hanas R and Ludvigsson J: Side effects and indwelling times of subcutaneous catheters for insulin injections: a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 10:73–83. 1990. View Article : Google Scholar : PubMed/NCBI

21 

Chiang CK, Ho TI, Peng YS, et al: Rosiglitazone in diabetes control in hemodialysis patients with and without viral hepatitis infection: effectiveness and side effects. Diabetes Care. 30:3–7. 2007. View Article : Google Scholar

22 

Zhang F, Lavan BE and Gregoire FM: Selective modulators of PPAR-gamma activity: Molecular aspects related to obesity and side-effects. PPAR Res. 2007:326962007. View Article : Google Scholar : PubMed/NCBI

23 

Evans RM, Barish GD and Wang YX: PPARs and the complex journey to obesity. Nat Med. 10:355–361. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang R, Dai L and Chen J: Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus. Exp Ther Med 9: 446-450, 2015.
APA
Wang, R., Dai, L., & Chen, J. (2015). Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus. Experimental and Therapeutic Medicine, 9, 446-450. https://doi.org/10.3892/etm.2014.2096
MLA
Wang, R., Dai, L., Chen, J."Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus". Experimental and Therapeutic Medicine 9.2 (2015): 446-450.
Chicago
Wang, R., Dai, L., Chen, J."Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus". Experimental and Therapeutic Medicine 9, no. 2 (2015): 446-450. https://doi.org/10.3892/etm.2014.2096
Copy and paste a formatted citation
x
Spandidos Publications style
Wang R, Dai L and Chen J: Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus. Exp Ther Med 9: 446-450, 2015.
APA
Wang, R., Dai, L., & Chen, J. (2015). Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus. Experimental and Therapeutic Medicine, 9, 446-450. https://doi.org/10.3892/etm.2014.2096
MLA
Wang, R., Dai, L., Chen, J."Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus". Experimental and Therapeutic Medicine 9.2 (2015): 446-450.
Chicago
Wang, R., Dai, L., Chen, J."Identification of a proliferator‑activated receptor-γ antagonist for the treatment of type 2 diabetes mellitus". Experimental and Therapeutic Medicine 9, no. 2 (2015): 446-450. https://doi.org/10.3892/etm.2014.2096
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team