Androgen suppression protects against hyposalivation and salivary gland damage in mice with type 2 diabetes

Abstract

Objective

Hyposalivation is one of the most common oral complications of type 2 diabetes (T2D). Sex hormone levels, which have been associated with hyposalivation, salivary gland atrophy, and inflammation, can be altered in T2D. However, the relationship between androgen levels and hyposalivation in the context of T2D is unknown. Therefore, this study investigated the role of gonadal androgen suppression on the function and histomorphometry of salivary glands in mice with T2D.

Methods

Four-week-old male C57BL/6 mice were divided into four groups: control, orchiectomy (ORQx), T2D, and ORQx-T2D. Orchiectomy was performed at eight weeks of age, and T2D was induced using a high-calorie diet and low-dose streptozotocin. At 20 weeks of age, the blood glucose levels, saliva secretion and quality, and serum testosterone were measured. The parotid and submandibular glands were retrieved, processed for histology, and sections were stained with hematoxylin and eosin, Sirius Red or immunohistochemically stained for α-amylase, interleukin (IL)-1, IL-6, IL-10, IL-17, and tumor necrosis factor-α.

Results

Mice with T2D exhibited decreased saliva secretion and quality, reduced α-amylase expression, and the number of acini. They also developed glandular fibrosis and acinar hypertrophy, along with increased in proinflammatory cytokines in both salivary glands. Androgen suppression in mice with T2D reduced hyperglycemia, normalized saliva secretion, decreased glandular fibrosis and acinar hypertrophy, increased α-amylase expression, and reduced proinflammatory cytokine expression in both glands.

Conclusions

Androgen suppression in mice with T2D reduces the development of hyposalivation and histomorphometric changes in the parotid and submandibular glands by modulating the inflammatory microenvironment.