Role of alpha2-adrenoceptors on the hyperglycaemic and insulin secretory effects derived from alpha1- and beta-adrenoceptor stimulation in the rabbit

J Auton Pharmacol. 1998 Oct;18(5):287-95. doi: 10.1046/j.1365-2680.1998.18596.x.

Abstract

1. In conscious fasted rabbits the insulin secretory response induced by the intravenous infusion of the alpha1-adrenoceptor agonist, amidephrine (10 microg kg(-1) min(-1)) was blocked by the simultaneous administration of clonidine (2 microg kg(-1) min(-1) i.v.). 2. The excitatory effect of amidephrine (10 microg kg(-1) min(-1)) on insulin secretion was similarly suppressed by the concomitant infusion of the selective alpha2-adrenoceptor agonist UK14304 (1 microg kg(-1) min(-1)). Both, the increase in blood glucose and the inhibition of insulin secretion found with UK14304 when infused alone were antagonized in rabbits previously treated with the very selective alpha2-adrenoceptor antagonist 2-methoxyidazoxan (1.5 microg kg(-1) min(-1)). 3. The combined administration of amidephrine (3 microg kg(-1) min(-1)) and isoprenaline (0.3 microg kg(-1) min(-1)) evoked a potentiated increase in insulin plasma levels in the face of a weak hyperglycaemia, an established reduction in blood pressure and tachycardia. 4. The potentiated insulin secretory response derived from alpha1- and beta-adrenoceptor stimulation was blunted by clonidine administration. In its presence a sustained hyperglycaemic response was found. 5. The increase in plasma lactate levels resulting from dual adrenoceptor stimulation (amidephrine: 10 microg kg(-1) min(-1) + salbutamol: 0.3 microg kg(-1) min(-1)) was smaller than the expected should addition or potentiation occurred. 6. Our results point to a possible physiological role played by alpha2-adrenoceptors on insulin secretion, since their stimulation by the endogenous catecholamines could lead to inhibition of insulin release, masking any potentiated response that otherwise should have appeared from alpha1- and beta-adrenoceptor stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Albuterol / pharmacology
  • Animals
  • Blood Glucose / analysis
  • Blood Pressure / drug effects
  • Brimonidine Tartrate
  • Clonidine / pharmacology
  • Ethanolamines / pharmacology
  • Heart Rate / drug effects
  • Hyperglycemia / physiopathology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Lactic Acid / blood
  • Male
  • Quinoxalines / pharmacology
  • Rabbits
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Receptors, Adrenergic, alpha-2 / physiology*
  • Receptors, Adrenergic, beta / physiology*

Substances

  • Adrenergic alpha-Agonists
  • Blood Glucose
  • Ethanolamines
  • Insulin
  • Quinoxalines
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Receptors, Adrenergic, beta
  • Lactic Acid
  • Brimonidine Tartrate
  • amidephrine
  • Clonidine
  • Albuterol