Skip to main content

Part of the book series: Medical Science Symposia Series ((MSSS,volume 18))

  • 85 Accesses

Abstract

Adult onset (Type 2) diabetes mellitus afflicts more than 100 million people worldwide, and its prevalence is soaring in developed countries with high fat diets and increasingly sedentary lifestyles. The development of insulin resistance is an early step in the onset of Type 2 diabetes. The glitazones, including rosiglitazone and pioglitazone, and tyrosine analogs GI262570 and GW1929 are promising new drugs for the treatment of Type 2 diabetes [1]. These drugs improve insulin sensitivity and reduce glucose levels in Type 2 diabetics by increasing glucose utilization in muscle and decreasing glucose production in the liver [2]. These drugs have the added therapeutic benefits of increasing high density lipoprotein cholesterol levels and decreasing triglyceride and free fatty acid (FFA) levels.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: From orphan receptors to drug discovery. J Med Chem 2000;43:527–50.

    Article  PubMed  CAS  Google Scholar 

  2. Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996;45:1661–69.

    Article  PubMed  CAS  Google Scholar 

  3. Spiegelman BM. PPAR-gamma: Adipogenic regulator and thiazolidinedione receptor. Diabetes 1998;47:507–14.

    Article  PubMed  CAS  Google Scholar 

  4. Brown KK, Henke BR, Blanchard SG, et al. A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. Diabetes 1999;48:1415–24.

    Article  PubMed  CAS  Google Scholar 

  5. Way JM, Harrington WW, Brown KK, et al. Comprehensive messenger ribonucleic acid profiling reveals that peroxisome proliferator-activated receptor gamma activation has coordinate effects on gene expression in multiple insulin-sensitive tissues. Endocrinology 2001;142:1269–77.

    Article  PubMed  CAS  Google Scholar 

  6. Shimkets RA, Lowe DG, Tai JT, et al. Gene expression analysis by transcript profiling coupled to a gene database query. Nature Biotechnol 1999;17:798–803.

    Article  CAS  Google Scholar 

  7. Flier JS, Hollenberg AN. ADD-1 provides major new insight into the mechanism of insulin action. Proc Natl Acad Sci USA 1999;96:14191–92.

    Article  PubMed  CAS  Google Scholar 

  8. Sreenan S, Keck S, Fuller T, Cockburn B, Burant CF. Effects of troglitazone on substrate storage and utilization in insulin-resistant rats. Am J Physiol 1999;276:E1119–29.

    PubMed  CAS  Google Scholar 

  9. Randle PJ. Regulatory interactions between lipids and carbohydrates: The glucose fatty acid cycle after 35 years. Diabetes Metab Rev 1998;14(4):263–83.

    Article  PubMed  CAS  Google Scholar 

  10. Bergman RN, Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 2000; 11:351–56.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Kliewer, S. (2002). PPARγ Mechanism of Action Studies. In: Fruchart, JC., Gotto, A.M., Paoletti, R., Staels, B., Catapano, A.L. (eds) Peroxisome Proliferator Activated Receptors: From Basic Science to Clinical Applications. Medical Science Symposia Series, vol 18. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1171-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1171-7_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5427-7

  • Online ISBN: 978-1-4615-1171-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics