Agmatine Ameliorates Insulin Resistance Induced in Rats

Background: Insulin resistance is a major metabolic disturbance often associated with glucocorticoid therapy. Dexamethasone (DEXA) is widely used clinically but may provoke hepatic dysfunction, oxidative stress, and impaired glucose homeostasis. Agmatine, a polyamine derivative, has been reported to exert antioxidant and anti-inflammatory effects. This study aimed to evaluate the protective role of agmatine against DEXA-induced insulin resistance in rats. Methods: Twenty adult male Wistar rats (180–220 g) were randomly allocated into three groups (n = 6 each): Control group: received standard chow only, DEXA group: administered DEXA (8 mg/kg/day, i.p., days 8–13), Agmatine + DEXA group: treated with agmatine (40 mg/kg/day, days 1–13) plus DEXA (8 mg/kg/day, i.p., days 8–13). On day 14, blood and liver samples were collected for biochemical assays. Serum ALT and AST were measured as liver function biomarkers. Hepatic malondialdehyde (MDA) was assessed as an oxidative stress marker. Fasting serum glucose (FSG), fasting serum insulin (FSI), and HOMA‑IR index were determined to evaluate insulin resistance. Results: DEXA administration significantly elevated ALT, AST, MDA, FSG, FSI, and HOMA‑IR compared to control. Agmatine treatment markedly reduced ALT, AST, and hepatic MDA levels relative to DEXA group. Agmatine also improved metabolic parameters, lowering FSG, FSI, and HOMA‑IR compared to DEXA group. Conclusion: Agmatine effectively mitigated DEXA-induced hepatic dysfunction, oxidative stress, and insulin resistance. These findings highlight its potential as a protective agent against glucocorticoid-provoked metabolic and tissue alterations.