Hyperglycemia contributes to the development of Leydig cell hyperplasia in male Spontaneously Diabetic Torii rats

Abstract

Spontaneously Diabetic Torii (SDT) rats are a well-known animal model of non-obese type 2 diabetes mellitus. Although this animal model has been studied extensively over the last decade, the incidence rates of Leydig cell hyperplasia and tumors in this model have not been reported. In this study, pathophysiological analyses of the testes were performed on male SDT rats, to understand the effect of insulin treatment on the development of Leydig cell hyperplasia and tumors and the expression of integrins and extracellular matrix proteins. Testicular Leydig cell hyperplasia and tumors were observed in SDT rats at 64 weeks of age but were rarely identified in Sprague-Dawley (SD) rats of the same age. Insulin treatment decreased plasma glucose and HbA1c levels, and interestingly, decreased the number of hyperplastic Leydig cell foci and Leydig cell tumors in treated animals. A similar reduction in the expression of Ki67 in these Leydig cell foci was also observed. In addition, insulin treatment decreased the expression of integrin α5, integrin β1, integrin αvβ3, fibronectin, and vitronectin in hyperplastic Leydig cell foci. These results suggest that insulin might decrease the incidence of Leydig cell hyperplasia by reducing Leydig cell proliferation and the expression of integrins and extracellular matrix proteins through the reduction of serum glucose concentrations in these animals.

Ejaculatory dysfunction in men with diabetes mellitus

“…PE is associated with decreased neurotransmission of serotonin, 5-HT 2C receptor hyposensitivity, and 5-HT 1A receptor hypersensitivity[ 63 ]. Accordingly, ejaculatory dysfunction due to changes in serotonergic transmission among diabetic animals could be anticipated; (7) There is adequate evidence to suggest that experimental diabetes in different animal models (STZ rats, spontaneously diabetic BB rats, BB/WOR diabetic rats, and spontaneously diabetic Torii rats) is associated with low testosterone levels[ 64 - 70 ]. The pathogenesis of hypogonadism in diabetic animal models may include impaired hypothalamic or pituitary signaling[ 34 , 71 , 72 ], deficiency of gonadotropic hormones, or blockade of their actions[ 73 , 74 ], and/or primary Leydig cell defect in steroidogenesis due to lack of stimulating effect of insulin[ 74 - 76 ].…”