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 45Ca2+ 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 86Rb+, the addition of alpha-fluorocinnamate or quercetin caused a modest diminution in efflux rate whilst enhanced rates of 86Rb+ 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.
Best
L
L
Department of Medicine, University of Manchester, U.K.
Trebilcock
R
R
Tomlinson
S
S
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical
D002934:Cinnamates; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D002731:4-Chloromercuribenzenesulfonate; D011794:Quercetin