Effect of Insulin Therapy on Vagina in Diabetic Rat

Lee, Sang Nyeong; Lee, Song Eun; Bae, Mi Ok; Nam, Kwang IL; Park, Kwang Sung; Bae, Choon Sang; Kim, Baik Yoon; Park, Sung Sik; Ahn, Kyu Youn

Abstract

The most commonly reported sexual problems in diabetic women are sexual arousal disorder and a lack of vaginal lubrication. The aims of this study were to investigate the vaginal structural changes and expressions of TGF-beta1, Ec-NOS and estrogen receptor alphaby histochemistry, immunohistochemistry and Western blot analysis in diabetic and insulin-treated diabetic rats. The mean blood glucose levels were significantly increased in the diabetic rats (453+/-88.4 mg/dL)compared to the control group (79+/-6 mg/dL)and insulin-treated diabetic rats (56.7+/-0.6 mg/dL).The vaginal wall in control rat showed 6~11 layered stratified squamous epithelial lining and submucosal smooth muscle, connective tissue and vasculatures. In diabetic rat, the vaginal epithelium was reduced to 2~6 layers and the submucosal vasculatures were decreased n size and number.Collagen fibers were increased and irregularly distorted arrangement. Insulin-treated diabetic rat showed similar morphologic features as control rat.In diabetic rat, TGF-beta1 expression was upregulated by 1.65 times and Ec-NOS expression was 40% downregulated compared to control and insulin-treated diabetic rats in Western blot analysis. In control and insulin-treated diabetic rats, TGF-beta1 immunoreactivity was detected in fibroblasts and the collagen fibers, Ec-NOS immunoreactivity in the endothelial cells of blood vessels, and estrogen receptor alphaimmunoreactivity in the basal and intermediate cell layers of stratified squamous epithelium, smooth muscle fibers, and nerve fibers. In diabetic rat, expression of TGF-beta1, Ec-NOS, and estrogen receptor alphawas exhibited comparable cellular patterns of labeling, but signal intensity was increased in TGF-beta1 and decreased in Ec-NOS and estrogen receptor alpha. These results suggest that vaginal tissue fibrosis in diabetes mellitus may be caused by altered expression of TGF-beta1, NOS and estrogen. It also mplies that sexual arousal disorder and lack of vaginal lubrication in the diabetic women could be protected or delayed by controlling blood glucose levels.