Dipeptidyl peptidase IV inhibitor improves the salivary gland histology of spontaneously diabetic mice.

OBJECTIVES: The incretin-based therapy might be effective in patients possessing certain levels of preserved pancreatic beta-cells. However, doubts still exist regarding the efficacy of this atment in the recovery of tissues damaged by type 1 diabetes. Thus, the objective of this study was to evaluate the treatment with MK0431 in salivary glands of spontaneously diabetic mice, focusing mainly on the possible therapeutic and hypoglycaemic effects of this dipeptidyl peptidase IV inhibitor in the recovery of these salivary tissues. METHODS AND RESULTS: Twenty mice were divided into two groups of 10 animals each: group I (NOD diabetic/untreated) and group II (NOD diabetic MK0431/treated). The group II was treated during 4 weeks with MK0431 mixed in the food. The group I was maintained in the same way without receiving, however, any treatment. Glucose levels were monitored during treatment and salivary glands samples were collected at the end of treatment for the histological examination under both transmitted and polarized light microscopy. High glucose levels were observed in untreated animals, while in animals with treatment, reduction of these levels was observed. Tissue restructuring was also observed in animals submitted to therapy with MK0431, mainly in relation to the attempt to extracellular matrix reorganization. CONCLUSIONS: According to results, the treatment with this dipeptidyl peptidase IV inhibitor contributed to the general homeostasis of the organism and to the reestablishment of both epithelial and stromal compartments which were damaged by the hyperglycaemic condition, demonstrating that the incretin-based therapy may be an important complementary treatment for the type 1 diabetic condition.

Estrogen and insulin replacement therapy modulates the expression of insulin-like growth factor-I receptors in the salivary glands of diabetic mice.

Diabetes mellitus results in various complications, also compromising the salivary glands. Hormone levels and interactions with cellular receptors are altered, intensifying the damage caused by this disease. Hormone replacement therapy alone or combined with other treatments may reverse this damage, but doubts still exist regarding the efficacy of this procedure. The objective of this study was to evaluate the effect of estrogen replacement therapy combined with insulin treatment on salivary secretory cells and on the expression of insulin-like growth factor (IGF)-I receptors in salivary glands of spontaneously diabetic (NOD) mice. Twenty-five mice were divided into five groups of five animals each: group I (NOD diabetic), group II (NOD diabetic treated with insulin), group III (NOD diabetic treated with estrogen), group IV (NOD diabetic treated with insulin and estrogen), and group V (control Balb/c mice). Group II received insulin, group III received estrogen, and group IV received insulin plus estrogen administered daily for 20 days. Groups I and V received saline for the same period of time to simulate treatment. Glucose and estrogen levels were monitored during treatment, and salivary gland samples were collected at the end of treatment for stereological analysis and immunofluorescence detection of IGF-I receptors. Tissue restructuring and regulation of IGF-I receptors expression were observed in animals submitted to estrogen replacement therapy plus insulin. Estrogen effectively promoted the recovery of salivary secretory cells, demonstrating that this hormone alone, and especially when combined with insulin, might be important for the reversal of hyperglycemia-induced tissue injury.