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Molecular Medicine

, Volume 17, Issue 1–2, pp 4–11 | Cite as

Modulation of Insulin Sensitivity and Caveolin-1 Expression by Orchidectomy in a Nonobese Type 2 Diabetes Animal Model

  • Yoon Sin Oh
  • Tae Sup Lee
  • Gi Jeong Cheon
  • Ik-Soon Jang
  • Hee-Sook Jun
  • Sang Chul Park
Research Article

Abstract

Previously, we found that male JYD mice developed type 2 diabetes but female mice did not, and that decreased expression levels of caveolin-1 were correlated with the development of a diabetic phenotype in these mice. Therefore, we hypothesized that sex hormones affect the expression of caveolin-1 and contribute to the development of insulin resistance and hyperglycemia in JYD mice. We used glucose and insulin tolerance tests to examine insulin sensitivity in male, female and orchidectomized male JYD mice. Glucose uptake was analyzed by using 18F-fluorodeoxyglucose positron emission tomography. We also examined insulin-signaling molecules and caveolin proteins in various tissues in these mice by Western blotting. In addition, we examined changes of caveolin-1 expression in L6 skeletal muscle cells treated with 17-β estradiol or dihydroxytestosterone. We found that glucose and insulin tolerance were impaired and hyperglycemia developed in male, but not female, JYD mice. Expression of insulin-signaling molecules such as insulin receptor, protein kinase B, and glucose transporter-4 were decreased in male JYD mice compared with female mice. Orchidectomized JYD male mice showed improved glucose and insulin tolerance with a concomitant increase in the expression of insulin-signaling molecules and caveolin-1 in adipose tissue and skeletal muscle. Moreover, 17-β-estradiol treatment increased the expression of caveolin-1 in differentiated skeletal muscle cells. We conclude that sex hormones modulate the expression of caveolin-1 and insulin-signaling molecules, subsequently affecting insulin sensitivity and the development of type 2 diabetes in JYD mice.

Notes

Acknowledgments

This study was supported by grants from the Aging and Apoptosis Research Center of the Korea Science and Engineering Foundation (RII-2002-097-05001-0, RII-2002-097-00001-0), National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (MEST) (M20702010002-08N0201-00200), and the Innovative Research Institute for Cell Therapy (A062260), Korea. We thank S-K Woo for technical assistance with imaging analysis and A Kyle for editorial assistance.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  1. 1.Lee Gil Ya Cancer and Diabetes InstituteGachon University of Medicine and ScienceYeonsu-ku, IncheonKorea
  2. 2.Molecular Imaging Research CenterKorea Institute of Radiological and Medical SciencesSeoulKorea
  3. 3.Korea Basic Science InstituteDaegeonKorea
  4. 4.Department of Biochemistry and Molecular BiologySeoul National University College of MedicineChongno Ku, SeoulKorea

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