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

Neurosci Lett. 2004 Mar 25;358(2):111-4. doi: 10.1016/j.neulet.2004.01.011.


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 micromol/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 micromol/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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agmatine / pharmacology*
  • Agmatine / therapeutic use
  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood*
  • Diabetes Mellitus, Experimental / drug therapy
  • Dose-Response Relationship, Drug
  • Imidazoline Receptors
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Drug / metabolism*


  • Blood Glucose
  • Imidazoline Receptors
  • Receptors, Drug
  • Agmatine