The pancreatic β-cell recognition of insulin secretagogues XIII effects of sulphydryl reagents on cyclic AMP

Chloromercuribenzene-p-sulphonic acid (0.1 mM) or 5,5′-dithiobis-(2-nitrobenzoic acid) (1 mM) alone had no effect on cyclic AMP in microdissected pancreatic islets of non-inbred ob/ob mice. In the presence of 1 mM 3-isobutyl-1-methylxanthine, the mercurial increased and the disulphide decreased the cyclic AMP content. Both sulphydryl reagents stimulated insulin release whether 3-isobutyl-1-methylxanthine was present or not. The effects of chloromercuribenzene-p-sulphonic acid on insulin release and cyclic AMP were markedly inhibited by 1 mM 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid. In the absence of phosphodiesterase inhibitor, iodoacetamide (0.1 mM) potentiated insulin release in response to 20 mM glucose but had no demonstrable effect on cyclic AMP. In the presence of 20 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine, however, iodoacetamide increased the cyclic AMP content although insulin release was not further enhanced. It is suggested that chloromercuribenzene-p-sulphonic acid and iodoacetamide may stimulate the formation of cyclic AMP in pancreatic islets. This effect could contribute to the insulin-releasing action of these stimuli, although promotion of cyclic AMP is probably not the sole mechanism by which sulphydryl reagents stimulate secretion.