Iodoacetate and iodoacetamide-induced alterations of pancreatic alpha- and beta-cell responses.
Iodoacetate and iodoacetamide were compared as to their capacity to block islet glycolysis and interfere with glucose inhibition of glucagon release and glucose stimulation of insulin release. Glycolysis was measured in isolated rat islet by the rate of lactate formation from 27 mM glucose. Hormone release was investigated by perfusing isolated rat pancreas with a 10 mM mixture of 19 amino acids, with and without 5 mM glucose. In perfusion experiments, lactate (2.5 mM) and pyruvate (0.5 mM) were present to provide alternate source of energy independent of glycolysis. Iodoacetate was about twice as potent as iodoacetamide in blocking glycolysis in islets, 0.2 and 0.5 mM, respectively being needed for complete inhibition of lactate production. Levels of either agent lower than 0.05 mM did not affect lactate accumulation. Iodoacetate, at the level which completely inhibited glycolysis did not interfere with the permissive action of glucose for insulin release. In contrast, iodoacetamide at a level (0.05 mM) which had no effect on lactate production, changed the response of the beta-cell dramatically: amino acids now released insulin even in the absence of glucose and insulin release by 5 mM glucose alone was greatly augmented. Both thiol reagents at 0.025 mM concentration completely prevented glucose from suppressing amino acid stimulated glucagon release, iodoacetamide being more potent than iodoacetate. These data indicate that the opposite physiological actions of glucose in alpha and beta-cells are in each case dissociable from the fuel function of the sugar molecule, and the results best support the concept that glucose and thiol reagents effect insulin and glucagon secretion by acting on sulfhydryl groups related to receptor sites in the alpha-and beta-cell membrane.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D007460:Iodoacetamide / Q000494:pharmacology*; D007461:Iodoacetates / Q000494:pharmacology*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D013268:Stimulation, Chemical
D000596:Amino Acids; D007328:Insulin; D007461:Iodoacetates; D011955:Receptors, Drug; D005934:Glucagon; D005947:Glucose; D007460:Iodoacetamide