Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic β -cells
Abstract
Glucose stimulates insulin secretion from the pancreatic beta-cell by increasing the cytosolic calcium concentration. It is believed that this increment results mainly from Ca2+ influx through dihydropyridine-sensitive calcium channels because insulin secretion is abolished by dihydropyridine antagonists and is potentiated by dihydropyridine agonists. Glucose may influence Ca2+ influx through these channels in two ways: either by regulating the beta-cell membrane potential or by biochemical modulation of the channel itself. The former mechanism is well established. Glucose metabolism, by closing ATP-sensitive K+ channels, depolarizes the beta-cell membrane and initiates Ca2+-dependent electrical activity, with higher glucose concentrations further increasing Ca2+ influx by raising the frequency of action potentials. We show here that glucose metabolism also increases calcium influx directly, by modulating the activity of dihydropyridine-sensitive Ca2+ channels.
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In mouse β-cells, glucose increases the whole-cell Ca2+ current and stimulates Ca2+ channel activity.
“Furthermore, in mouse β-cells, glucose increases the whole-cell Ca2+ current and stimulates Ca2+ channel activity (635).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [635]
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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
Self-citationGembal, M., Gilon, P., & Henquin, J. C. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115714 · Cited by 494 · see citing works
Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells
Olofsson, C. S., Göpel, S. O., Barg, S., Galvanovskis, J., Ma, X., Salehi, A., Rorsman, P., & Eliasson, L. (2002) · Pflügers Archiv · doi:10.1007/s00424-002-0781-5 · Cited by 290 · see citing works
Self-citationStimulus-secretion coupling in pancreatic β cells
Ashcroft, F. M., Proks, P., Smith, P. A., Ämmälä, C., Bokvist, K., & Rorsman, P. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240550007 · Cited by 255 · see citing works
Self-citationRegulation of two insulin granule populations within the reserve pool by distinct calcium sources
Hao, M., Li, X., Rizzo, M. A., Rocheleau, J. V., Dawant, B. M., & Piston, D. W. (2005) · Journal of Cell Science · doi:10.1242/jcs.02684 · Cited by 56 · see citing works
- Authors
- Smith, P. A., Rorsman, P., & Ashcroft, F. M.
- Affiliations
- University of Oxford (GB)
- Venue
- Nature
- Published
- 1989-11
- Volume
- 342
- Issue
- 6249
- Pages
- 550-553
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2062100108
- Cited by
- 143
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 2 · 2019: 1 · 2017: 2 · 2014: 3 · 2013: 3
- FWCI
- 22.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- dihydropyridine-sensitive calcium channels, glucose metabolism, pancreatic beta cells, insulin secretion, calcium influx, ATP-sensitive potassium channels, channel modulation, glucose-stimulated insulin secretion
- MeSH terms
- Animals, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Calcium, Dihydropyridines, Electric Conductivity, Glucose, Islets of Langerhans, Membrane Potentials, Calcium Channels, Mice, In Vitro Techniques
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