Cited by 144Pancreatic function and diabetesMetabolism, Diabetes, and CancerDiabetes Treatment and Management

The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.

Open access
Heimberg, H, De Vos, A, Moens, K, Quartier, E, Bouwens, L, Pipeleers, D, Van Schaftingen, E, Madsen, O +1 more·1996·Proceedings of the National Academy of Sciences

Abstract

Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase.

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Crossref · 10.1073/pnas.93.14.7036

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Authors
Heimberg, H., De Vos, A., Moens, K., Quartier, E., Bouwens, L., Pipeleers, D., Van Schaftingen, E., Madsen, O., & Schuit, F.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • Diabetes Research Center, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Venue
Proceedings of the National Academy of Sciences
Published
1996-07-09
Volume
93
Issue
14
Pages
7036-7041
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2030386197
Cited by
142
References
36
Citations by year
2025: 3 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 5 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 3 · 2012: 9
FWCI
6.65
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • VUBIR (Vrije Universiteit Brussel) (publishedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
glucokinase, alpha cells, glucagon secretion, glucose detection, glucose phosphorylation, glucose utilization, glucagonoma, GLUT2, glucose homeostasis, pancreatic islets
MeSH terms
Animals, Base Sequence, Brain, Cells, Cultured, Glucagon, Glucagonoma, Glucokinase, Glucose, Glutamine, Homeostasis, Insulin, Islets of Langerhans, Liver, Male, Molecular Sequence Data, Monosaccharide Transport Proteins, Pancreatic Neoplasms, RNA, Messenger, Transcription, Genetic, Tumor Cells, Cultured, 1-Methyl-3-isobutylxanthine, Polymerase Chain Reaction, Rats, Wistar, DNA Primers, DNA, Complementary, Glucose Transporter Type 2, Rats

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