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PMID: 8335003 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 12 ·No. 7 ·1993-07-00 ·Pages 2873-9

Heimberg H, De Vos A, Vandercammen A, Van Schaftingen E, Pipeleers D, Schuit F

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.

MeSH Terms
Amino Acids/metabolism Animals Biological Transport Cells, Cultured DNA Gene Expression Glucokinase/metabolism Glucose/metabolism,pharmacology Glucose Transporter Type 2 Glutamate Dehydrogenase/metabolism Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism Hexokinase/metabolism Islets of Langerhans/drug effects,enzymology,metabolism Male Monosaccharide Transport Proteins/genetics,metabolism Oxidation-Reduction Peptide Fragments/metabolism Phosphorylation Proinsulin/biosynthesis Protein Biosynthesis Pyruvate Dehydrogenase Complex/metabolism RNA, Messenger/metabolism Rats Rats, Wistar
Chemicals
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
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Heimberg H
Department of Biochemistry, Vrije Universiteit Brussel, Belgium.
De Vos A
Vandercammen A
Van Schaftingen E
Pipeleers D
Schuit F
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-07-00
Pages
2873-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413540
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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