Effect of Sitagliptin (Januvia) on the Thyroid Gland of Adult Male Albino Rats in an Experimental Model of Type II Diabetes Mellitus - (Biochemical, Histological and Immunohistochemical Studies)

摘要

Type II diabetes mellitus is a major global health problem and there is ongoing research for new treatments to manage the disease. The glucagon-like peptide-1 receptor (GLP-1R) controls the physiological response to the incretin peptide, GLP- 1, Sitglaptin, is a DPP- IV inhibitor and through its effect on receptor GLP-1 seems to have much wider effects on the function and survival of cells that express its receptor. Also, inhibitors of dipeptidyl peptidase-IV (DPP-IV) are a novel class of anti-diabetes drugs; inhibiting the breakdown of incretins, they increase their biological availability and thus decrease blood glucose level. In addition to regulating glucose homeostasis, DPP-IV has many diverse functions, such as modulating cell growth, cellular differentiation and transformation and it can disturb the immune function. Effect of DPP-IV inhibitors in humans are scarce, it has a risk of infections and the tendency towards a higher incidence of some tumors which fall in line with experimental evidence suggesting the possibility of their adverse immunological and oncological effects. Aim of work : This study was set to evaluate the possible side effects of Sitagliptin on the thyroid gland of the adult male rats after induction of diabetes mellitus II by Alloxan. Material and Methods: Thirty adult male albino rats were divided into three equal groups: control group, diabetic non treated group and diabetic rats treated with therapeutic dose of Sitagliptin (100 mg/kg/day) for eight weeks. At the end of the experimental period, the hormones of thyroid function, calcitonin in addition to histological, ultra structural and immune-cytochemical examinations of the thyroid tissue calcitonin and caspase 3. Also, evaluation of the oxidative markers were carried. The results: showed that treatment with Sitagliptin caused significant increase in free T3 and calcitonin level (P<0.001) with significant increase of oxidative markers (P<0.001). Histological examination showed evidence of stratification and focal hyperplasia of the follicular cells with strong PAS reaction in addition to engorgement of Golgi system and dilatation of the rough endoplasmic reticulum with presence of multiple secondary lysosomes. Immunohistochemical results showed significant increase (P<0.001) of calcitonin immunopositive expression of thyroid C-cells which appeared stronger than normal, in addition to marked significant increase (P<0.001) in area percent of caspase-3 immunopositive cells which appeared as massive dense brown cytoplasmic deposits.Conclusion s :Sitagliptin administration induced changes in the thyroid tissues leading to quantitative and qualitative alterations in the hormonal levels and enhancement of apoptosis.