Comparative Therapeutic Effect of Single/Combined Administration of Saxagliptin, Metformin and Intranasal Insulin on Dexamethasone Induced Insulin Resistance in Wistar Rat Model

Abstract

Summary: Glucocorticoids have therapeutic benefits in the management of several inflammatory and immunological disorders. Despite these medicinal effects, they have the drawback of causing metabolic disorders such as hyperglycemia, insulin resistance etc., which is known to be a key indicator of metabolic syndrome. Metabolic syndrome is a major predisposing factor to type 2 diabetes mellitus and cardiomyopathy. This study was designed to compare and evaluate the effects of saxagliptin, metformin and intranasal insulin (when used singly or in combination) on dexamethasone induced insulin resistance. Fifty-six female rats were randomly assigned into eight groups. Group 1 represented the control; Group 2 was administered with dexamethasone (1mg/kg) and served as untreated group. Other groups were administered dexamethasone(1mg/kg) and treated with singly/combinations of intranasal insulin (2IU); metformin and (40mg/kg) and saxagliptin (8mg/kg). Treatments were given for period of one week. At the end of the study, blood samples were collected for biochemical assays such as lipid profile, serum insulin, glucagon, adiponectin, glucokinase enzymes and glucose-6-phosphatase enzymes. Representative pancreases were excised for histological examination. Results showed that dexamethasone (1mg/kg) induced hyperglycemia, hyperinsulinemia, dyslipidemia, increased glucose-6-phosphatase, decreased glucokinase, impaired glucose tolerance and disrupted the structural integrity of the pancreas. Treatment with saxagliptin, metformin and their combinations significantly decreased blood glucose level, decreased LDL Level, improved glucose tolerance and offered protection to the pancreatic islet cells. In conclusion, the selected hypoglycemic agents used in present study ameliorate the dexamethasone induced hyperglycemia and insulin resistance of which the combination of metformin with saxagliptin showed greater efficacy.