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

EMBO J. 1993 Jul;12(7):2873-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Biological Transport
  • Cells, Cultured
  • DNA
  • Gene Expression
  • Glucokinase / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Glucose Transporter Type 2
  • Glutamate Dehydrogenase / metabolism
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Hexokinase / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism*
  • Male
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Oxidation-Reduction
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Proinsulin / biosynthesis
  • Protein Biosynthesis
  • Pyruvate Dehydrogenase Complex / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Amino Acids
  • Glucose Transporter Type 2
  • Monosaccharide Transport Proteins
  • Peptide Fragments
  • Pyruvate Dehydrogenase Complex
  • RNA, Messenger
  • glyceraldehyde 3-phosphate dehydrogenase (304-313)
  • DNA
  • Proinsulin
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Glutamate Dehydrogenase
  • Hexokinase
  • Glucokinase
  • Glucose