Evidence map›Paper›PMID 20519125›Full record

ArticleCell metabolism2010

GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.

Yang Z De Marinis, Albert Salehi, Caroline E Ward, Quan Zhang, Fernando Abdulkader, Martin Bengtsson, Orit Braha, Matthias Braun, Reshma Ramracheya, Stefan Amisten and 11 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05616273 (Stimulated Glucagon as a Biomarker of Hypoglycemic Risk in Type 1 Diabetes), which is not on this map. Cited by 143 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
143citing papers in PubMed, 2 pooled it
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05616273 completednot on this mapstarted 2023, after this paper: background citation

Stimulated Glucagon as a Biomarker of Hypoglycemic Risk in Type 1 Diabetes

TypeobservationalSponsorUniversity of ExeterRan2023 to 2025Enrolled62ConditionsType 1 Diabetes, HypoglycemiaArmsMixed Meal Tolerance Test (MMTT), Arginine Stimulation Test (AST), Home Finger Prick Sample
3 · Its place in the literature

Who cites it

143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 255 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Susceptibility of Glucose Regulation to Social Isolation.bioRxiv : the preprint server for biology · 2025
    Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024 · on this map
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

83 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 4 countries.

Yang Z De Marinis *Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Albert Salehi *Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Caroline E Ward *Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Quan Zhang *Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Fernando AbdulkaderOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Martin BengtssonOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Orit BrahaOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Matthias BraunOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Reshma RamracheyaOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Stefan AmistenOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Abdella M HabibCambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, UK.
Yusuke MoritohOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Enming ZhangLund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Frank ReimannCambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, UK.
Anders RosengrenLund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Tadao ShibasakiDivision of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Fiona GribbleCambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, UK.
Erik RenströmLund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Susumu SeinoDivision of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
Lena EliassonLund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, SE20502 Malmö, Sweden.
Patrik RorsmanOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Churchill Hospital · GBLund University · SEUniversity of Cambridge · GBKobe University · JPUniversidade de São Paulo · BR

Funding

Medical Research Council G0600717Medical Research Council G0801995Wellcome Trust 084210Wellcome Trust 088357
6 · The paper itself

Abstract

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1-10 nM) and high (10 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on alpha cell electrical activity but selectively inhibits N-type Ca(2+) channels and exocytosis. Adrenaline stimulates alpha cell electrical activity, increases [Ca(2+)](i), enhances L-type Ca(2+) channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca(2+) channels via a small increase in intracellular cAMP ([cAMP](i)). Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP](i).

Indexed as

ExocytosisAnimalsCalcium Channels, L-TypeCalcium Channels, N-TypeCarrier ProteinsCells, CulturedColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesEpinephrineGlucagonGlucagon-Like Peptide 1Guanine Nucleotide Exchange FactorsIslets of LangerhansMembrane PotentialsMiceCalcium Channels, L-TypeCalcium Channels, N-TypeCarrier ProteinsColforsinCyclic AMPCyclic AMP-Dependent Protein KinasesEpinephrineGlucagonGlucagon-Like Peptide 1Guanine Nucleotide Exchange FactorsRapgef4 protein, mouse

Identifiers

PMID20519125
PMCPMC4310935
OpenAlexW2041346929

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.