|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Physiology, University of Arizona, Tucson, Arizona, United States
* To whom correspondence should be addressed. E-mail: brooksh{at}email.arizona.edu.
Changes in the estrogen/testosterone balance at menopause may negatively influence the development of diabetic kidney disease. Furthermore, recent studies suggest that changes in hormone levels during perimenopause may influence disease development. Injection of 4-vinylcyclohexene diepoxide (VCD) in B6C3F1 mice induces gradual ovarian failure, preserving both the perimenopausal (peri-ovarian failure) and menopausal (post-ovarian failure) periods. To address the impact of the transition into menopause on the development of diabetes and diabetic kidney damage, we used STZ-induced diabetes in the VCD model of menopause. After six weeks of STZ-induced diabetes, blood glucose was significantly increased in post-ovarian failure (post-OF) diabetic mice compared to cycling diabetic mice. In peri-ovarian failure (peri-OF) diabetic mice blood glucose levels trended higher but were not significantly different from cycling diabetic mice, suggesting a continuum of worsening blood glucose across the menopausal transition. Cell proliferation, an early marker of damage in the kidney, was increased in post-OF diabetic mice compared to cycling diabetic mice, as measured by PCNA immunohistochemistry. In post-OF diabetic mice mRNA abundance of early growth response-1 (Egr-1), collagen-4
1 and matrix metalloproteinase-9 were increased and 3
-hydroxysteroid dehydrogenase 4 (3
-HSD4) and transforming growth factor-
2 (TGF
2) were decreased compared to cycling diabetic mice. In peri-OF diabetic mice mRNA abundance of Egr-1 and 3
-HSD4 were increased, and TGF
2 was decreased compared to cycling diabetic mice. This study highlights the importance and utility of the VCD model of menopause, as it provides a physiologically relevant system for determining the impact of the menopausal transition on diabetes and diabetic kidney damage.
This article has been cited by other articles:
![]() |
S. K. Banerjee, K. R. McGaffin, N. M. Pastor-Soler, and F. Ahmad SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states Cardiovasc Res, October 1, 2009; 84(1): 111 - 118. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Maric Sex, diabetes and the kidney Am J Physiol Renal Physiol, April 1, 2009; 296(4): F680 - F688. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Rivera, P. J. Christian, S. L. Marion, H. L. Brooks, and P. B. Hoyer Steroidogenic Capacity of Residual Ovarian Tissue in 4-Vinylcyclohexene Diepoxide-Treated Mice Biol Reprod, February 1, 2009; 80(2): 328 - 336. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |