Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport

• Published in: The EMBO journal 1993-07, Vol.12 (7), p.2873-2879
• Main Authors: Heimberg, H, Vos, A. de, Vandercammen, A, Schaftingen, E. van, Pipeleers, D, Schuit, F
• Format: Article
• Language: English
• Subjects: active transport; Amino Acids - metabolism; animal proteins; Animals; Biological and medical sciences; Biological Transport; carbohydrate metabolism; Cells, Cultured; DNA; Endocrine pancreas; enzyme activity; Fundamental and applied biological sciences. Psychology; Gene Expression; glucokinase; Glucokinase - metabolism; glucose; Glucose - metabolism; Glucose - pharmacology; glucose transporter; Glucose Transporter Type 2; Glutamate Dehydrogenase - metabolism; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; hexokinase; Hexokinase - metabolism; Hormones. Régulation; islets of Langerhans; Islets of Langerhans - drug effects; Islets of Langerhans - enzymology; Islets of Langerhans - metabolism; Male; messenger RNA; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; oxidation; Oxidation-Reduction; Peptide Fragments - metabolism; Phosphorylation; Proinsulin - biosynthesis; Protein Biosynthesis; Pyruvate Dehydrogenase Complex - metabolism; Rats; Rats, Wistar; RNA, Messenger - metabolism; uptake; Vertebrates: endocrinology
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1993.tb05949.x

Rat beta-cells differ in their individual rates of glucose-induced insulin biosynthesis and release. This functional heterogeneity has been correlated with intercellular differences in metabolic redox responsiveness to glucose. The present study compares glucose metabolism in two beta-cell 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 higher than in low responsive beta-cells, whereas their leucine and glutamine oxidation was only 10-50% higher. This heterogeneity in glucose metabolism cannot be attributed to differences in GLUT2 mRNA levels or in glucose transport. In both cell subpopulations, the rates of glucose transport (13-19 pmol/min/10(3) beta-cells) were at least 50-fold higher 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 glucokinase activity than low responsive beta-cells and their glucokinase mRNA level was 100% higher. Furthermore, glucose phosphorylation via low Km 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.