Activation of I2-imidazoline receptors may ameliorate insulin resistance in fructose-rich chow-fed rats

Agmatine, an endogenous ligand of imidazoline receptors, was employed to screen the effect on insulin resistance in rats induced by a diet containing 60% fructose. Single intravenous (i.v.) injection of agmatine sulfate for 30 min decreased the plasma glucose concentrations in a dose-dependent manner from 0.5 mg/kg to 3 mg/kg in rats received 4-week fructose-rich chow without an alteration of systolic blood pressure. The plasma glucose lowering action of agmatine (1 mg/kg, i.v.) was abolished by the pretreatment with BU224 (1 mg/kg, i.v.) at sufficient dosage to block I2-imidazoline receptors. In addition, the value of glucose-insulin index, the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test, showing an index of in vivo insulin sensitivity was reversed by the same treatment with agmatine in fructose-rich chow-fed rats; this action was also blocked by BU224. Our results suggest that activation of I2-imidazoline receptor to improve insulin action on glucose disposal can be considered for targeting glucose metabolism under insulin-resistant state.