Effects of possible beta-cell membrane label, metahexamide-isothiocyanate, on insulin release

To synthetize a specifically and covalently reacting label for the sulfonylurea receptor site, the sulfonylurea metahexmide was converted to its isothiocyano-derivative (MITC), and the effects of MITC on insulin release from the perfused rat pancreas were studied. MITC (2 micrometer) stimulated a large insulin release that persisted after the end of the MITC-infusion. At a higher concentration (50 micrometer) MITC produced only a short lasting stimulation, and thereafter inhibited either the sulfonylurea or the glucose-induced insulin release. It is suggested that the irreversible stimulation of insulin release by MITC reflects the convalent linkage of the label to the sulfonylurea receptor site, while excess isothiocyanate inhibited insulin release by reacting on less specific binding sites involved in the secretion process.