Relationship between D-glucose oxidation and glycolysis in tumoral pancreatic islet cells with either rapid or decreased cell growth.
The relationship between glucose oxidation and glycolysis was examined in tumoral pancreatic islet cells with either rapid or decreased cell growth. In the control RINm5F cells, the utilization of D-[5-3H]glucose progressively augmented at increasing concentrations of D-glucose (0.2 to 16.7 mM), whereas D-[6-14C]glucose oxidation reached its maximal value at about 3.0 mM D-glucose. The 14CO2/3HOH ratio progressively decreased at increasing hexose concentrations, being about 5-times higher at 0.2 than 10.0-16.7 mM. These experiments were repeated in cells cultured in the presence of D,L-alpha-difluoromethylornithine, which inhibits RINm5F cell proliferation. At 0.2 mM D-glucose, 14CO2 output was severely decreased but 3HOH production little affected, resulting in a marked fall of the 14CO2/3HOH ratio. On the contrary, at 16.7 mM D-glucose, 3HOH formation was more markedly decreased than 14CO2 output, resulting in an increased 14CO2/3HOH ratio. These findings provide a model for the interference of cell growth with D-glucose metabolism in islet cells. Rapid growth causes a preferential stimulation of the Krebs cycle relative to glycolysis at a low glucose concentration, whilst increasing glycolysis more than oxidation at high concentrations of the hexose.