Evidence map›Paper›PMID 39475504›Full record

ArticleDiabetes2025

Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells.

Alexander Hamilton, Quan Zhang, Rui Gao, Thomas G Hill, Albert Salehi, Jakob G Knudsen, Matthew B Draper, Paul R V Johnson, Patrik Rorsman, Andrei I Tarasov

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Review
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

10 authors.

Alexander HamiltonOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Quan ZhangOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Rui GaoOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Thomas G HillOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Albert SalehiUnit of Molecular Metabolism, Clinical Research Centre, Lund University Diabetes Centre, Lund University and Malmö University Hospital, Malmö, Sweden.
Jakob G KnudsenOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.ORCID 0000-0001-7237-8457
Matthew B DraperSchool of Biomedical Sciences, Ulster University, Coleraine, U.K.
Paul R V JohnsonOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Patrik RorsmanOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.
Andrei I TarasovOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and Churchill Hospital, Oxford, U.K.ORCID 0000-0002-8883-176X

Funding

Diabetes UK PhD Studentship, AHOxford Biomedical Research Council Fellowship, AIT
6 · The paper itself

Abstract

Smoking is widely regarded as a risk factor for type 2 diabetes because nicotine contributes to insulin resistance by desensitizing the insulin receptors in muscle, liver, or fat. Little is known, however, about the immediate regulation of islet hormonal output by nicotine, an agonist of ionotropic cholinergic receptors. We investigated this by imaging cytosolic Ca2+ dynamics in mouse and human islets using confocal microscopy and measuring glucagon secretion in response to the alkaloid from isolated mouse islets. Nicotine acutely stimulated cytosolic Ca2+ in glucagon-secreting α-cells but not in insulin-secreting β-cells. The 2.8- ± 0.5-fold (P < 0.05) increase in Ca2+, observed in >70% of α-cells, correlated well with a 2.5- ± 0.3-fold stimulation of glucagon secretion. Nicotine-induced elevation of cytosolic Ca2+ relied on influx from the extracellular compartment rather than release of the cation from intracellular depots. Metabotropic cholinergic signaling, monitored at the level of intracellular diacylglycerol, was limited to 69% of α-cells versus 94% of β-cells. We conclude that parasympathetic regulation of pancreatic islet hormone release uses different signaling pathways in β-cells (metabotropic) and α-cells (metabotropic and ionotropic), resulting in the fine-tuning of acetylcholine-induced glucagon exocytosis. Sustained nicotinic stimulation is, therefore, likely to attenuate insulin sensitivity by increasing glucagon release. ARTICLE HIGHLIGHTS:

Indexed as

GlucagonGlucagon-Secreting CellsNicotineSignal TransductionAnimalsCalciumHumansInsulin-Secreting CellsMaleMiceMice, Inbred C57BLReceptors, NicotinicCalciumGlucagonNicotineReceptors, Nicotinic

Identifiers

PMID39475504
PMCPMC11663815

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.