ACUTE STIMULATION OF PANCREATIC-ISLETS BY INHIBITORS OF LACTIC-ACID TRANSPORT

The transport of L-lactate into rat pancreatic islets and RINm5F insulinoma cells was inhibited by alpha-cyano-4-hydroxycinnamate, alpha-fluorocinnamate, quercetin and by p-chloromercuribenzene-sulphonic acid. The addition of each of these compounds to perifused islets resulted in an immediate, marked stimulation of insulin release. Enhanced insulin secretion was accompanied by a similarly rapid and pronounced increase in the rate of Ca-45(2+) efflux from pre-loaded, perifused islets. In general, these stimulatory effects were most pronounced in the presence of a threshold concentration of glucose (5 mM) in the perifusion medium. In islets pre-loaded with Rb-86+, the addition of alpha-fluorocinnamate or quercetin caused a modest diminution in efflux rate whilst enhanced rates of Rb-86+ outflow were apparent in the presence of 5 mM glucose. It is suggested that these inhibitors of lactic acid transport stimulate the beta-cell, at least in part, by increasing the intracellular: extracellular lactate gradient, thereby promoting the electrogenic efflux of endogenous lactate from the cell.