Calcium mobilization, prostaglandin E2 and alpha 2-adrenoceptor modulation of glucose utilization and insulin secretion in pancreatic islets.
alpha 2-Adrenoceptor agonists inhibit glucose-stimulated insulin release and glucose utilization in pancreatic islets. In isolated pancreatic islets of the rat, the Ca2+ channel agonists CGP-28392 and BAY-K-8644 increased insulin release in the presence of clonidine. Neither CGP-28392 nor BAY-K-8644 antagonized the effect of clonidine on glucose utilization. The Ca2+ ionophore, ionomycin, also did not affect glucose utilization in the presence or absence of clonidine. Glucagon partly reversed the effects of clonidine on insulin release, and it potentiated glucose-stimulated insulin release in the absence of clonidine. Glucagon reversed the effects of clonidine on glucose utilization. Amiloride antagonized the effects of clonidine on insulin secretion but did not enhance markedly glucose utilization in the presence or absence of clonidine. Carbamylcholine and arecoline reversed the effects of clonidine on glucose utilization and partly reversed the effects on insulin release in the absence of extracellular Ca2+. Prostaglandin (PG) E2, but not PGF2 alpha, inhibited glucose utilization in a time- and concentration-dependent manner. PGE2 also inhibited glucose-stimulated insulin release. Pertussis toxin blocked both actions of PGE2. The cyclooxygenase inhibitor indomethacin did not affect insulin release or glucose utilization in the presence of clonidine. Thus, elevated intracellular Ca2+ levels antagonize the effects of clonidine on insulin release, whereas other mediators appear to be required to alter glucose utilization.
Laychock
S G
SG
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0524.
Bilgin
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D015232:Dinoprostone / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D002120:Calcium Channel Agonists; D007328:Insulin; D011942:Receptors, Adrenergic, alpha; D005934:Glucagon; D005947:Glucose; D015232:Dinoprostone; D003000:Clonidine; D002118:Calcium