title: Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport.
abstract: 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.
authors.affiliation: Department of Biochemistry, Vrije Universiteit Brussel, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Heimberg
authors.forename: A
authors.initials: A
authors.lastname: De Vos
authors.forename: A
authors.initials: A
authors.lastname: Vandercammen
authors.forename: E
authors.initials: E
authors.lastname: Van Schaftingen
authors.forename: D
authors.initials: D
authors.lastname: Pipeleers
authors.forename: F
authors.initials: F
authors.lastname: Schuit
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004247:DNA; D015870:Gene Expression; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051273:Glucose Transporter Type 2; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011384:Proinsulin / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; C068142:glyceraldehyde 3-phosphate dehydrogenase (304-313); D004247:DNA; D011384:Proinsulin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005969:Glutamate Dehydrogenase; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose