Crabtree effect in tumoral pancreatic islet cells.
The relationship between glycolysis and respiration was examined in a model of pancreatic B-cell dysfunction, namely in tumoral insulin-producing cells of the RINm5F line. A rise in D-glucose concentration from 2.8 to 16.7 mM increased the utilization of D-[5-3H]glucose and production of [14C]lactate from D-[U-14C]glucose, whereas decreasing the oxidation of either D-[U-14C]glucose or D-[6-14C]glucose. Whereas 2.8 mM D-glucose augmented O2 uptake above basal value, a further rise in D-glucose concentration to 16.7 mM decreased respiration, which remained higher, however, than basal value. Whether at low or high concentration, D-glucose exerted a pronounced sparing action upon the oxidation of endogenous nutrients in cells prelabeled with either L-[U-14C]glutamine or [14C]palmitate and, nevertheless, augmented above basal value the rate of lipogenesis, ATP/ADP content, adenylate charge, and cytosolic NADH/NAD+ and NADPH/NADP+ ratios. The generation of ATP resulting from the catabolism of either exogenous D-glucose or endogenous nutrients was not affected by the rise in hexose concentration from 2.8 to 16.7 mM. Thus, in sharp contrast with the situation found in normal islet cells, a rise in D-glucose concentration, instead of stimulating mitochondrial oxidative events, caused, through a Crabtree effect, inhibition of hexose oxidation and O2 consumption in tumoral islet cells.
Sener
A
A
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Blachier
F
F
Malaisse
W J
WJ
D000227:Adenine Nucleotides / Q000378:metabolism; D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D008055:Lipids / Q000096:biosynthesis; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000227:Adenine Nucleotides; D007773:Lactates; D008055:Lipids; D010169:Palmitic Acids; D005973:Glutamine; D009243:NAD; D019308:Palmitic Acid; D019344:Lactic Acid; D009249:NADP; D005947:Glucose