Evidence mapPaperPMID 37494670Full record

ArticleDiabetes2023

Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells.

Sarah L Armour, Alexander Frueh, Margarita V Chibalina, Haiqiang Dou, Lidia Argemi-Muntadas, Alexander Hamilton, Georgios Katzilieris-Petras, Peter Carmeliet, Benjamin Davies, Thomas Moritz and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
8.9field-weighted citation impact, top 2% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 28 citations in OpenAlex.

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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

13 authors at 6 institutions in 5 countries.

Sarah L ArmourSection for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Alexander FruehSection for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Margarita V ChibalinaOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K.
Haiqiang DouDepartment of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Lidia Argemi-MuntadasNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Alexander HamiltonSection for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Georgios Katzilieris-PetrasSection for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Peter CarmelietLaboratory of Angiogenesis and Vascular Metabolism, Centre for Cancer Biology, Vlaams Instituut voor Biotechnologie (VIB), Department of Oncology, Leuven Cancer Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
Benjamin DaviesWellcome Centre for Human Genetics, University of Oxford, Oxford, U.K.
Thomas MoritzNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Lena EliassonDepartment of Clinical Sciences in Malmö, Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Malmö, Sweden.
Patrik RorsmanOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, U.K.
Jakob G KnudsenSection for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0001-7237-8457
University of Copenhagen · DKChurchill Hospital · GBCentre for Human Genetics · GBLund University · SESun Yat-sen University · CNUniversity of Gothenburg · SE

Funding

Medical Research Council MR/V011979/1Wellcome TrustWellcome Trust 203141/Z/16/Z
6 · The paper itself

Abstract

Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from α-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic α-cells remain unclear. Here we show that in α-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the α-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion. ARTICLE HIGHLIGHTS: It has become clear that dysregulation of glucagon secretion and α-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in α-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.

Indexed as

Glucagon-Secreting CellsIslets of LangerhansAdenosine TriphosphateAnimalsBlood GlucoseFatty AcidsGlucagonGlucoseHumansInsulinMiceAdenosine TriphosphateBlood GlucoseFatty AcidsGlucagonGlucoseInsulin

Identifiers

PMID37494670
PMCPMC10545563
OpenAlexW4385268385

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.