Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action.
Exposure of rat pancreatic beta cells in monolayer culture to 2 mmol streptozotocin (STZ)/l for 1 h followed by thorough washing inhibited their uptake of [14C]nicotinamide and [3H]2-deoxyglucose [( 3H]2-DG) to about 50% and also reduced the intracellular ATP concentration to 50% of that in control cells. These changes were not due to a lethal cytotoxic effect of STZ, because cell viability, as estimated by succinic dehydrogenase activity, was 90% of that of control cells. Oligomycin and carbonylcyanide-m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, caused a dose-dependent decrease in intracellular ATP concentration while maintaining high cell viability. These ATP-depleted cells showed a decrease in insulin release and an inhibition of the uptake of [14C]nicotinamide and [3H]2-DG in a dose-dependent manner. Therefore oligomycin and CCCP reproduced the same effects as those found in beta cells treated with STZ. These results suggest that the uptake of nicotinamide and 2-DG by beta cells might be regulated by their intracellular ATP concentration. The decreased uptake of nicotinamide in ATP-depleted beta cells caused by STZ might explain the lack of protective effect of nicotinamide against STZ cytotoxicity when administered after the latter. Furthermore, the radiotracer experiments demonstrated that the transport of nicotinamide by intact beta cells was inhibited in a dose-dependent manner by 2-DG and vice versa, i.e. the transport of 2-DG was inhibited by nicotinamide. These findings suggest the existence of a common transport mechanism in beta cells responsible for the uptake of nicotinamide and 2-DG, the transport of which is known to occur by facilitated diffusion.
Sofue
M
M
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Yoshimura
Y
Y
Nishida
M
M
Kawada
J
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002250:Carbon Radioisotopes; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology*; D014316:Tritium
D002250:Carbon Radioisotopes; D007328:Insulin; D009840:Oligomycins; D014316:Tritium; D009536:Niacinamide; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D013311:Streptozocin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose