The coupling of metabolic to secretory events in pancreatic islets: inhibition by 2-cyclohexene-1-one of the secretory response to cyclic AMP and cytochalasin B.
In rat pancreatic islets perifused in the presence of 2-cyclohexene-1-one (CHX; 1.0 mM), the secretory response to either D-glucose or 2-ketoisocaproate, but not that evoked by the association of L-leucine and L-glutamine, was severely decreased. This coincided with a decreased stimulation of [45Ca] efflux from prelabelled islets, whereas the inhibitory action of D-glucose or 2-ketoisocaproate upon both [86Rb] and [45Ca] efflux appeared little or not affected. In the presence of D-glucose, the islets exposed to CHX were virtually unresponsive to either forskolin, theophylline or cytochalasin B. A severe decrease in the secretory response to forskolin was also observed in CHX-treated islets exposed to L-leucine and L-glutamine. Except for a somewhat lower sensitivity to NaF, no major change in adenylate cyclase activity or cyclic AMP production was observed in CHX-treated islets. The activity of protein kinase A was decreased in such islets but its responsiveness to cyclic AMP appeared unaltered. Transglutaminase activity was severely decreased in homogenates derived from CHX-treated islets. These findings suggest that CHX, possibly by lowering the GSH content of islet cells, impairs the functional capacity of the effector system for insulin release, in addition to and independently of any effect that it may exert upon nutrient catabolism and cationic fluxes in the islet cells.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D003571:Cytochalasin B / Q000494:pharmacology*; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007651:Keto Acids / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D011503:Transglutaminases / Q000378:metabolism
D003510:Cyclohexanes; D003512:Cyclohexanones; D007328:Insulin; D007651:Keto Acids; D005576:Colforsin; D003571:Cytochalasin B; C028215:2-cyclohexen-1-one; C013082:alpha-ketoisocaproic acid; D013806:Theophylline; D000242:Cyclic AMP; D011503:Transglutaminases; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D005947:Glucose