Role of thiol groups in insulin release: studies with poorly permeating disulphides

Research output: Contribution to journalArticle

Abstract

At a concentration of 1.0 mM, 6,6' dithiodinicotinic acid and 5,5' dithiobis (2 nitrobenzoic acid) stimulated insulin release from microdissected pancreatic islets of hereditary obese (ob/ob) mice. Microperifusion experiments showed that the secretory responses occurred promptly upon exposure to the sulfhydryl reagents. Perifusion with 6,6' dithiodinicotinic acid induced a sustained enhancement of insulin release without any signs of multiphasic secretion. This reagent induced a similar release pattern at both 3 and 17 mM glucose, although the high glucose concentration appeared to potentiate the effect of 6,6' dithiodinicotinic acid. The dynamics of insulin release in response to 5,5' dithiobis (2 nitrobenzoic acid) depended markedly, however, on the accompanying glucose concentration. At 0 and 3 mM glucose an initial peak of release was followed by a steady decline towards the basal release rate, whereas at 17 mM glucose 5,5' dithiobis (2 nitrobenzoic acid) produced a sustained enhancement of secretion. The omission of calcium significantly inhibited insulin release in response of either of the two disulfides, although clear cut stimulation was still obtained. In marked contrast, 17 glucose clucose did not elicit even an initial peak of insulin release when calcium was omitted from the perifusion medium. 6,6' Dithiodinicotinic acid (0.01-1.0 mM) had no effect on the oxidation of (U 14C)D glucose. Significant inhibition of glucose oxidation was obtained with 0.1 and 1.0 mM 5,5' dithiobis (2 nitrobenzoic acid), whereas at a concentration of 0.01 mM this reagent stimulated oxidation. Since the disulfides do not readily penetrate cell membranes, the results are consistent with the hypothesis that insulin release is regulated by relatively superficial thiol groups in the β cell plasma membrane. However, further studies are necessary to exclude the possibility that the observed effects were due to small amounts of disulphide entering the β cells.

Details

Authors
  • B. Hellman
  • L. A. Idahl
  • A. Lernmark
  • J. Sehlin
  • I. B. Täljedal
External organisations
  • Umeå University
Original languageEnglish
Pages (from-to)792-801
JournalMolecular Pharmacology
Volume9
Issue number6
Publication statusPublished - 1973 Dec 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes