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Cited by 142Pancreatic function and diabetesAmino Acid Enzymes and MetabolismIon channel regulation and function

Electrogenic arginine transport mediates stimulus‐secretion coupling in mouse pancreatic beta‐cells.

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Smith, P A, Sakura, H, Coles, B, Gummerson, N, Proks, P, Ashcroft, F M·1997·The Journal of Physiology
DOI 10.1113/jphysiol.1997.sp021955PMC PMC1159281
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Abstract

1. We have investigated the mechanism by which L‐arginine stimulates membrane depolarization, an increase of intracellular calcium ([Ca2+]i) and insulin secretion in pancreatic beta‐cells. 2. L‐Arginine failed to affect beta‐cell metabolism, as monitored by NAD(P)H autofluorescence. 3. L‐Arginine produced a dose‐dependent increase in [Ca2+]i, which was dependent on membrane depolarization and extracellular calcium. 4. The cationic amino acids L‐ornithine, L‐lysine, L‐homoarginine (which is not metabolized) and NG‐monomethyl‐L‐arginine (L‐NMMA, a nitric oxide synthase inhibitor) produced [Ca2+]i responses similar to that produced by L‐arginine. The neutral nitric oxide synthase inhibitors NG‐nitro‐L‐arginine (L‐NNA) and N omega‐monomethyl‐L‐arginine (L‐NAME) also increased [Ca2+]i. D‐Arginine was ineffective. 5. L‐Arginine did not affect whole‐cell Ca2+ currents or ATP‐sensitive K+ currents, but produced an inward current that was carried by the amino acid. 6. The reverse transcriptase‐polymerase chain reaction demonstrated the presence of messenger RNA for the murine cationic amino acid transporters mCAT2A and mCAT2B within the beta‐cell. 7. L‐Arginine did not affect beta‐cell exocytosis as assayed by changes in cell capacitance. 8. Our data suggest that L‐arginine elevates [Ca2+]i and stimulates insulin secretion as a consequence of its electrogenic transport into the beta‐cell. This uptake is mediated by the mCAT2A transporter.

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  • Electrogenic uptake of positively charged arginine or lysine evokes a small depolarizing current.

    “Electrogenic uptake of positively charged arginine (or lysine) evokes a small depolarizing current (636).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [636]

    The Abstract reports that L-arginine produces an inward current carried by the amino acid and links its electrogenic uptake to beta-cell depolarization. It reports a similar calcium response to L-lysine, but does not say that lysine evokes an inward current or describe the current as small. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Arginine and lysine enter the β-cell via the y+ family of cationic amino acid transporters.

    “They enter the β-cell via the y+ family of cationic amino acid transporters (636).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [636]

    The Abstract (page not specified in our copy) says that arginine enters mouse β-cells by electrogenic transport mediated by mCAT2A. It reports a similar calcium response to lysine, but does not establish that lysine enters β-cells through a y+ transporter. A cited reference identifies mCAT genes with y+-type transport. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Smith, P. A., Sakura, H., Coles, B., Gummerson, N., Proks, P., & Ashcroft, F. M.
Affiliations
University of Oxford (GB)
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
1997-03-15
Volume
499
Issue
3
Pages
625-635
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.1997.sp021955
PMC
PMC1159281
OpenAlex
W2027103431
Cited by
142
References
1
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 1 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 8
FWCI
6.71
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
Keywords
L-arginine, pancreatic beta cells, insulin secretion, intracellular calcium, membrane depolarization, cationic amino acid transporters, nitric oxide synthase inhibitors, L-NMMA, L-NNA, L-ornithine, L-lysine, L-homoarginine, amino acid uptake, exocytosis
MeSH terms
Insulin Secretion, Aniline Compounds, Animals, Arginine, Biological Transport, Calcium, Carrier Proteins, Electric Conductivity, Enzyme Inhibitors, Exocytosis, Fluorescent Dyes, Insulin, Islets of Langerhans, Kinetics, Membrane Glycoproteins, Membrane Potentials, Membrane Proteins, Nitric Oxide, Receptors, Virus, RNA, Messenger, Xanthenes, Alternative Splicing, Nitric Oxide Synthase, omega-N-Methylarginine, NG-Nitroarginine Methyl Ester, Nitroarginine, Mice

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