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Modulation of insulin sensitivity and caveolin-1 expression by orchidectomy in a nonobese type 2 diabetes animal
Yoon Sin Oh1, Tae Sup Lee, Gi Jeong Cheon
1Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.
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 (18)F-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.
Insights
Sex hormones influence caveolin-1 expression, impacting insulin resistance and type 2 diabetes development in JYD mice. Male mice showed impaired glucose and insulin tolerance, which improved after orchidectomy.
Area of Science:
- Endocrinology
- Metabolic Diseases
- Molecular Biology
Background:
- Male JYD mice develop type 2 diabetes, unlike females, with decreased caveolin-1 expression linked to the diabetic phenotype.
- Sex hormones are hypothesized to modulate caveolin-1 expression, contributing to insulin resistance and hyperglycemia.
Purpose of the Study:
- To investigate the role of sex hormones in regulating caveolin-1 expression and its impact on insulin sensitivity and type 2 diabetes in JYD mice.
- To analyze the effects of androgens and estrogens on insulin signaling pathways and glucose metabolism.
Main Methods:
- Glucose and insulin tolerance tests were performed on male, female, and orchidectomized male JYD mice.
- Positron emission tomography with (18)F-fluorodeoxyglucose was used to assess glucose uptake.
- Western blotting analyzed insulin-signaling molecules and caveolin proteins in various tissues.
- In vitro studies examined caveolin-1 expression in L6 skeletal muscle cells treated with 17-β estradiol or dihydroxytestosterone.
Main Results:
- Male JYD mice exhibited impaired glucose/insulin tolerance and hyperglycemia, unlike females.
- Expression of key insulin-signaling molecules (insulin receptor, protein kinase B, glucose transporter-4) was reduced in male mice.
- Orchidectomy in male mice improved glucose/insulin tolerance and increased insulin-signaling molecule and caveolin-1 expression in adipose tissue and skeletal muscle.
- 17-β-estradiol treatment elevated caveolin-1 expression in differentiated skeletal muscle cells.
Conclusions:
- Sex hormones play a critical role in modulating caveolin-1 expression and insulin signaling.
- This modulation by sex hormones subsequently affects insulin sensitivity and the development of type 2 diabetes in JYD mice.
