Impairment by aminooxyacetate of ionic response to nutrients in pancreatic islets.
Aminooxyacetate, an inhibitor of transamination reactions, was recently reported to prevent the induction of a more reduced state in the cytosolic redox couple, as normally evoked by glucose or 2-ketoisocaproate in rat pancreatic islets. The cationic effects of aminooxyacetate were examined, therefore, in perifused islets prelabeled with either 86Rb or 45Ca. Aminooxyacetate augmented the outflow of 86Rb from the islets whether in the absence or presence of an exogenous nutrient and slightly impaired the capacity of nutrients, especially 2-ketoisocaproate, to decrease 86Rb outflow. Aminooxyacetate abolished the nutrient-induced rise in 45Ca efflux that normally results from the stimulation by glucose or 2-ketoisocaproate of 40Ca influx into the islet cells. Aminooxyacetate, however, failed to suppress the early inhibitory effect of nutrients on 45Ca efflux. The alteration by aminooxyacetate of the cationic response to nutrient secretagogues coincided with a suppression of insulin release, whereas the cationic response to a nonnutrient stimulation by a high concentration of extracellular K+ was unaffected by aminooxyacetate. These findings suggest that the induction of a more reduced cytosolic redox state represents an essential link between metabolic events and both the decrease in K+ conductance and stimulation of Ca2+ inflow in the process of nutrient-induced insulin release.
D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000378:metabolism
D000085:Acetates; D000625:Aminooxyacetic Acid; D011189:Potassium Chloride; D005947:Glucose; D012413:Rubidium; D002118:Calcium