A Study For Metformin Improving Metabolic Disorders Induced By Glucocorticoids

Background:Glucocorticoids (GCs) are widely applied in clinical therapy for anti-inflammatory and immunosuppressive purpose. However, particularly when glucocorticoids are given for extended periods with higher doses, glucocorticoids are associated with multiple adverse outcomes. The metabolic disorders is one of them, including, but are not limited to, increase in insulin resistance, hyperglycemia, dyslipidemia and muscle wasting.Objective:The goals of this study was (1) to develop a in vivo rodent model of dexamethasone (Dex)-induced metabolic disorders, and (2) to investigate the therapeutic benefits of Metformin (Met) on the Dex-induced metabolic disorders.Methods:The rodent model of Dex-induced metabolic disorders model was established as two ways:(1) acute high-dose Dex model, in which male SD rats were fed by High Fat Diet (HFD) for 8 weeks, and then received Dex at the dose of 0. 5mg/kg/day (intraperitoneal injection, i.p.) for 7 days; and (2) chronic low dose Dex model, in which male SD rats were treated with Dex at the dose of 0.05mg/kg/day (i.p.) for 8 weeks. In our study, the metabolic disorders induced by Dex were evaluated by assessments of body weight, food intake, fasting blood glucose, and triglyceride (TG). The insulin resistance was assessed with ITTMetformin (Met) is an oral antihyperglycemic drug that has been widely used in the treatment of metabolic disorders in clinical. Met was selected in our study at two doses of 100 and 200 mg/kg/day (i.p.) to treat animals with metabolic disorders induced by Dex for evaluation of its therapeutic benefits.Results:HFD resulted in an increase in body weight and TG level (p<0.01), with elevation of body insulin resistance. Acute dosing Dex (0.5mg/kg) for 7 days induced a significant reduction of body weight(p<0.01)and food intake(p<0.01)and increase in insulin resistance, accompanied with significant hyperglycemia, compared with control group. The treatment with a low dose of Met (100mg/kg/day didn’t show any significant effect on the metabolic disorders, but the high dose of Met (200mg/kg/day) improved insulin resistance and depressed Dex induced elevation of blood glucose (p<0.05) and TG (p<0.05).Chronic dosing Dex (0.05mg/kg) for 8 weeks resulted in decrease in body weight (p<0.01), TG (p<0.01), and increase in insulin resistance, reflected by decrease in insulin sensitivity index (ISI) (p<0.01) and increase in plasma insulin level (p<0.01), compared with control group. Treatment with Met (both doses of 100 and 200 mg/kg/day) improved Dex-induced elevation of insulin resistance and reduced plasma levels of insulin and TG (both p<0.01).Conclusion:Both acute high-dose Dex and chronic low-dose Dex induced the development of metabolic disorders, associated with significantly increased insulin resistance and hyperglycemia (with high-dose of Dex). We also demonstrated that Met can effectively improve body’s insulin resistance and dyslipidemia, and especially reduced Dex-induced elevation of hyperglycemia. The therapeutic treatment with Metformin could be potential clinical beneficial.