Glucose metabolism in insulin-producing tumoral cells.
Homogenates of insulin-producing tumoral cells catalyzed the phosphorylation of glucose, mannose, and fructose. The kinetics of phosphorylation at increasing glucose concentrations, the inhibitory effect of glucose 6-phosphate, and the comparison of results obtained with distinct hexoses indicated the presence of both low-Km hexokinase-like and high-Km enzymatic activities, the results being grossly comparable to those collected in normal pancreatic islets. Relative to protein content, the glucose-phosphorylating enzymatic activity was higher in tumoral than normal islet cells. The activity of other enzymes was either lower (glutamate dehydrogenase), moderately higher (phosphoglucomutase, lactate dehydrogenase) or considerably greater (ornithine decarboxylase) in tumoral than in normal islet cells. In intact tumoral cells, incubated under increasing glucose concentrations, the oxidation of D-[U-14C]glucose and the output of lactic and pyruvic acids reached a close-to-maximal value at 2.8 mM glucose. The ratios for glucose oxidation/utilization and lactate/pyruvate output were much lower in tumoral than in normal islet cells. Although glucose caused a modest increase in insulin output from the tumoral cells, this effect was saturated at a low glucose concentration (2.8 mM) and less marked than that of other secretagogues (e.g., L-leucine, L-ornithine, or forskolin). Thus, despite a close-to-normal enzymatic equipment for glucose phosphorylation, the tumoral cells displayed severe abnormalities in the metabolism and secretory response to this hexose. These findings point to regulatory mechanisms distal to glucose phosphorylation in the control of glucose metabolism in insulin-producing cells.
D000818:Animals; D002460:Cell Line; D005941:Glucokinase / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000378:metabolism; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D007328:Insulin; D005973:Glutamine; D005941:Glucokinase; D005947:Glucose