The stimulus-secretion coupling of glucose-induced insulin release XXVI. Are the secretory and fuel functions of glucose dissociable by iodoacetate?
Iodoacetate inhibits glyceraldehyde-3-phosphate dehydrogenase activity in pancreatic islets and causes a time- and dose-related inhibition of glucose oxidation and lactate output by the islets. High concentrations of the drug (0.3 mM or more) fail to affect Ba2+-induced insulin secretion but inhibit glucose-stimulated proinsulin biosynthesis, 45Ca net uptake and insulin release. A mixture of fumarate, glutamate, and pyruvate, the oxidation of which is only partially reduced by iodoacetate, fails to protect the B-cell against the inhibitory effect of the drug. These findings are compatible with the view that glycolysis plays an essential role in the process of glucose-induced insulin release. At low concentrations of iodoacetate (up to 0.2 mM), the reduction in glucose metabolism coincides with a partial inhibition of proinsulin biosynthesis. However, the expected reduction in 45Ca net uptake and subsequent insulin release is masked by a concomitant facilitating action of iodoacetate, possibly due to interference with native ionophoretic processes. It is concluded that iodoacetate is not an adequate tool to dissociate, if they are dissociable, the fuel and secretory functions of glucose.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007461:Iodoacetates / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007773:Lactates / Q000378:metabolism; D010084:Oxidation-Reduction; D011384:Proinsulin / Q000096:biosynthesis; D051381:Rats
D007328:Insulin; D007461:Iodoacetates; D007773:Lactates; D001464:Barium; D011384:Proinsulin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005947:Glucose; D002118:Calcium