A POSSIBLE ROLE FOR GLYCERALDEHYDE TRANSPORT IN THE STIMULATION OF HIT-T15 INSULINOMA CELLS

D-Glyceraldehyde was transported into HIT-T15 cells at a linear rate f or approx. 2 min and appeared to be unsaturable up to a concentration of 50 mM. Evidence was obtained for an electrogenic component of uptak e of the triose. The rate of D-glyceraldehyde transport was also reduc ed in the absence of Na+, suggesting that a component of uptake was Na f-linked. Transport of D-glyceraldehyde could be prevented by N-ethylm aleimide but not significantly by p-chloromercuribenzenesulphonic acid , L-glyceraldehyde, nor by a number of inhibitors of known transport s ystems. However, D-glyceraldehyde transport was inhibited by alpha-cya no-4-hydroxycinnamate, an inhibitor of some anion transport systems. D -Glyceraldehyde caused a marked depolarization of HIT-TIS cells accomp anied by a rise in cytosolic [Ca2+] and [Na+] and a gradual intracellu lar acidification. The glyceraldehyde-induced rise in cytosolic [Na+] and intracellular acidification, but not the depolarization or rise in cytosolic [Ca2+], were reduced by dithiothreitol and 5-aminoguanidine , compounds which form chemical adducts with alpha-ketoaldehydes. Incu bation of HIT cells with either D- or L-glyceraldehyde resulted in the formation of large amounts of D-lactate, the end product of methylgly oxal metabolism via the glyoxalase pathway. It is suggested that the d epolarizing action of glyceraldehyde is the result, at least in part, of its electrogenic transport, probably via Na+-coupled entry into HIT cells involving an unidentified transport system. The intracellular a cidification and a component of the increase in cytosolic [Na+] may be largely due to the presence of one or more dicarbonyl contaminants in the glyceraldehyde preparation.