HETEROGENEITY IN GLUCOSE SENSITIVITY AMONG PANCREATIC BETA-CELLS IS CORRELATED TO DIFFERENCES IN GLUCOSE PHOSPHORYLATION RATHER THAN GLUCOSE-TRANSPORT

Rat beta-cells differ in their individual rates of glucose-induced ins ulin biosynthesis and release. This functional heterogeneity has been correlated with intercellular differences in metabolic redox responsiv eness to glucose. The present study compares glucose metabolism in two beta-celt subpopulations that have been separated on the basis of the presence (high responsive) or absence (low responsive) of a metabolic redox shift at 7.5 mM glucose. Mean rates of glucose utilization and glucose oxidation in high responsive beta-cells were 2- to 4-fold high er than in low responsive beta-cells, whereas their leucine and glutam ine oxidation was only 10-50% higher. This heterogeneity in glucose me tabolism cannot be attributed to differences in GLUT2 mRNA levels or i n glucose transport. In both cell subpopulations, the rates of glucose transport (13-19 pmol/min/10(3) beta-cells) were at least 50-fold hig her than corresponding rates of glucose utilization. On the other hand , rates of glucose phosphorylation (0.3-0.7 pmol/min/10(3) beta-cells) ranged within those of total glucose utilization (0.2-0.4 pmol/min/10 (3) beta-cells). High responsive beta-cells exhibited a 60% higher glu cokinase activity than low responsive beta-cells and their glucokinase mRNA level was 100% higher. Furthermore, glucose phosphorylation via low K(m) hexokinase was detected only in the high responsive beta-cell subpopulation. Heterogeneity in glucose sensitivity among pancreatic beta-cells can therefore be explained by intercellular differences in glucose phosphorylation rather than in glucose transport.