Activation of imidazoline receptor by agmatine to lower plasma glucose in streptozotocin-induced diabetic rats

In the present study, we use agmatine, an endogenous ligand, to investigate the role of imidazoline receptor in plasma glucose regulation in streptozotocin-induced diabetic rats (STZ-diabetic rats). After injection into the central lateral ventral (i.c.v.) of fasting STZ-diabetic rats for 30 min, agmatine produced plasma glucose lowering action in a concentration-dependent manner without alteration the mean arterial pressure (MAP). However, the plasma glucose was markedly raised in STZ-diabetic rats receiving similar injection of clonidine at dose (1 mumol/rat, i.c.v.) sufficient to lower MAP. Mediation of alpha(2)-adrenoceptor in this action of agmatine seems unlikely. The plasma glucose lowering action of agmatine (1 mumol/rat, i.c.v.) was abolished by the pretreatment with BU-224 at concentration (100 nmol/rat) sufficient to block cerebral I-2-imidazoline receptors. Also, this action of agmatine in STZ-diabetic rats disappeared by spinal cord truncation between C6 and C7. Activation of cerebral I-2-imidazoline receptor by agmatine can thus be considered for the lowering of plasma glucose. In conclusion, we suggest that an activation of I-2-imidazoline receptors in the brain may lower plasma glucose without insulin in animal. (C) 2004 Elsevier Ireland Ltd. All rights reserved.