Metabolic Fate of Glucose in Purified Islet Cells
Open accessAbstract
Previous studies in rat islets have suggested that anaplerosis plays an important role in the regulation of pancreatic beta cell function and growth. However, the relative contribution of islet beta cells versus non-beta cells to glucose-regulated anaplerosis is not known. Furthermore, the fate of glucose carbon entering the Krebs cycle of islet cells remains to be determined. The present study has examined the anaplerosis of glucose carbon in purified rat beta cells using specific 14C-labeled glucose tracers. Between 5 and 20 mM glucose, the oxidative production of CO2 from [3,4-14C]glucose represented close to 100% of the total glucose utilization by the cells. Anaplerosis, quantified as the difference between 14CO2 production from [3,4-14C]glucose and [6-14C]glucose, was strongly influenced by glucose, particularly between 5 and 10 mM. The dose dependence of glucose-induced insulin secretion correlated with the accumulation of citrate and malate in beta(INS-1) cells. All glucose carbon that was not oxidized to CO2 was recovered from the cells after extraction in trichloroacetic acid. This indirectly indicates that lactate output is minimal in beta cells. From the effect of cycloheximide upon the incorporation of 14C-glucose into the acid-precipitable fraction, it could be calculated that 25% of glucose carbon entering the Krebs cycle via anaplerosis is channeled into protein synthesis. In contrast, non-beta cells (approximately 80% glucagon-producing alpha cells) exhibited rates of glucose oxidation that were (1)/(3) to (1)/(6) those of the total glucose utilization and no detectable anaplerosis from glucose carbon. This difference between the two cell types was associated with a 7-fold higher expression of the anaplerotic enzyme pyruvate carboxylase in beta cells, as well as a 4-fold lower ratio of lactate dehydrogenase to FAD-linked glycerol phosphate dehydrogenase in beta cells versus alpha cells. Finally, glucose caused a dose-dependent suppression of the activity of the pentose phosphate pathway in beta cells. In conclusion, rat beta cells metabolize glucose essentially via aerobic glycolysis, whereas glycolysis in alpha cells is largely anaerobic. The results support the view that anaplerosis is an essential pathway implicated in beta cell activation by glucose.
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Almost all glucose entering glycolysis proceeds into the Krebs cycle in β-cells.
“An important aspect of glucose metabolism in the β-cell is that almost all the glucose entering glycolysis proceeds into the Krebs cycle (602) (520).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [602]
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Cites
Regulation of hepatic fatty acid oxidation and ketone body production
McGarry, J. D., & Foster, D. W. (1980) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.49.070180.002143 · Cited by 1,460 · see citing works
Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression.
De Vos, A., Heimberg, H., Quartier, E., Huypens, P., Bouwens, L., Pipeleers, D., & Schuit, F. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118308 · Cited by 425 · see citing works
Self-citationHeimberg, H., De Vos, A., Pipeleers, D., Thorens, B., & Schuit, F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.15.8971 · Cited by 188 · see citing works
Self-citationThe glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.
Heimberg, H., De Vos, A., Moens, K., Quartier, E., Bouwens, L., Pipeleers, D., Van Schaftingen, E., Madsen, O., & Schuit, F. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7036 · Cited by 142 · see citing works
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Research works printed but not linked: 2
- Henquin, J. C. (1994) in Joslin's Diabetes Mellitus (Kahn, C. R., and Weir, G. C., eds) pp. 56 -80, Lea & Febiger, Malvern, PA 4.
- Heimberg, H., De Vos, A., Moens, K., Quartier, E., Bouwens, L., Pipeleers, D., Van Schaftingen, E., Madsen, O., and Schuit, F. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 7036 -7041
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Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
Muoio, D. M., & Newgard, C. B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2327 · Cited by 1,177 · see citing works
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
The Role of Oxidative Stress and Hypoxia in Pancreatic Beta-Cell Dysfunction in Diabetes Mellitus
Gerber, P. A., & Rutter, G. A. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6755 · Cited by 654 · see citing works
Regulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599 · see citing works
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451 · see citing works
Self-citationRegulation of ATP production by mitochondrial Ca2+
Tarasov, A. I., Griffiths, E. J., & Rutter, G. A. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.03.003 · Cited by 319 · see citing works
Glucose or Insulin, but not Zinc Ions, Inhibit Glucagon Secretion From Mouse Pancreatic α-Cells
Ravier, M. A., & Rutter, G. A. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1789 · Cited by 264 · see citing works
Xin, Y., Dominguez Gutierrez, G., Okamoto, H., Kim, J., Lee, A.-H., Adler, C., Ni, M., Yancopoulos, G. D., Murphy, A. J., & Gromada, J. (2018) · Diabetes · doi:10.2337/db18-0365 · Cited by 191 · see citing works
Simmons, R. A., Suponitsky-Kroyter, I., & Selak, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505695200 · Cited by 194 · see citing works
Detimary, P., Dejonghe, S., Ling, Z., Pipeleers, D., Schuit, F., & Henquin, J.-C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.51.33905 · Cited by 159 · see citing works
Self-citationOlsen, H. L., Theander, S., Bokvist, K., Buschard, K., Wollheim, C. B., & Gromada, J. (2005) · Endocrinology · doi:10.1210/en.2005-0800 · Cited by 156 · see citing works
Anaplerotic roles of pyruvate carboxylase in mammalian tissues
Jitrapakdee, S., Vidal-Puig, A., & Wallace, J. C. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5410-y · Cited by 149 · see citing works
In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion
Maechler, P., Carobbio, S., & Rubi, B. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.12.006 · Cited by 140 · see citing works
Boucher, A., Lu, D., Burgess, S. C., Telemaque-Potts, S., Jensen, M. V., Mulder, H., Wang, M.-Y., Unger, R. H., Sherry, A. D., & Newgard, C. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401167200 · Cited by 136 · see citing works
Mitochondrial signals drive insulin secretion in the pancreatic β-cell
Wiederkehr, A., & Wollheim, C. B. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.07.016 · Cited by 133 · see citing works
Shah, S., Iqbal, M., Karam, J., Salifu, M., & McFarlane, S. I. (2007) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1629 · Cited by 115 · see citing works
Hasan, N. M., Longacre, M. J., Stoker, S. W., Boonsaen, T., Jitrapakdee, S., Kendrick, M. A., Wallace, J. C., & MacDonald, M. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804170200 · Cited by 88 · see citing works
Grubelnik, V., Markovič, R., Lipovšek, S., Leitinger, G., Gosak, M., Dolenšek, J., Valladolid-Acebes, I., Berggren, P.-O., Stožer, A., Perc, M., et al. (2020) · Royal Society Open Science · doi:10.1098/rsos.191171 · Cited by 32 · see citing works
Modelling of energy-driven switch for glucagon and insulin secretion
Grubelnik, V., Zmazek, J., Markovič, R., Gosak, M., & Marhl, M. (2020) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2020.110213 · Cited by 15 · see citing works
A computational systems analysis of factors regulating α cell glucagon secretion
Fridlyand, L. E., & Philipson, L. H. (2012) · Islets · doi:10.4161/isl.22193 · Cited by 12 · see citing works
- Authors
- Schuit, F., De Vos, A., Farfari, S., Moens, K., Pipeleers, D., Brun, T., & Prentki, M.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Corresponding author
- Schuit, Frans
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-07
- Volume
- 272
- Issue
- 30
- Pages
- 18572-18579
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1987417071
- Cited by
- 421
- References
- 4
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 13 · 2022: 13 · 2021: 23 · 2020: 17 · 2019: 16 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 19 · 2014: 24 · 2013: 14 · 2012: 21
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Canadian Diabetes Association
- Vrije Universiteit Brussel
- Université de Genève
- Medical Research Council Canada
- Medical Research Council
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- glucose metabolism, pancreatic beta cells, anaplerosis, TCA cycle, glucose oxidation, insulin secretion, pyruvate carboxylase, alpha cells, lactate dehydrogenase, glycerol-3-phosphate dehydrogenase, pentose phosphate pathway, aerobic glycolysis, protein synthesis, citrate, malate
- MeSH terms
- Animals, Cycloheximide, Flavin-Adenine Dinucleotide, Flow Cytometry, Glucose, Glycerolphosphate Dehydrogenase, Islets of Langerhans, L-Lactate Dehydrogenase, Malates, Male, Models, Chemical, Oxidation-Reduction, Protein Synthesis Inhibitors, Pyruvate Carboxylase, Rats, Wistar, Pyruvic Acid, Citric Acid, Rats
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