Rapid and reversible secretion changes during uncoupling of rat insulin-producing cells.

To determine whether insulin secretion is affected by a block- age of gap junctions between B cells, we have studied the se- cretion of rat pancreatic islets of Langerhans, primary dis- persed islet cells, and cells of the RINm5F line, during short- term exposure to heptanol. Within minutes, this alkanol blocked gap junctions between the B cells of intact islets and abolished their normal secretory response to glucose. These two changes were rapidly and fully reversible after return of the islets to control medium. We further found that heptanol had no significant effect on the glucose-stimulated secretion of single B cells but inhibited that of B cell pairs. In the clone of RINm5F cells, whose junctional coupling and D-glyceralde- hyde-induced stimulation of insulin release by aggregated cells were also inhibited by heptanol, this alkanol did not perturb intracellular pH and Ca2+ and the most distal steps of the secretion pathway. In summary, a gap junction blocker af- fected the secretion of insulin-producing cells by a mechanism which is dependent on cell contact and is not associated with detectable pleiotropic perturbations of the cell secretory ma- chinery. The data provide evidence for the involvement of junctional coupling in the control of insulin secretion. ( J. Clin. Invest. 1990. 86:759-768.) Key words: B cells * calcium * gap junctions,, pancreatic islets * reverse hemolytic plaque assay X 104 cells per ml were plated initially. The number of cells labeled by Lucifer yellow was determined on photographs of the intact clusters, which were taken immediately after each injection.