Evidence mapPaperPMID 30720465Full record

ArticleJCI insight2019

β Cell tone is defined by proglucagon peptides through cAMP signaling.

Megan E Capozzi, Berit Svendsen, Sara E Encisco, Sophie L Lewandowski, Mackenzie D Martin, Haopeng Lin, Justin L Jaffe, Reilly W Coch, Jonathan M Haldeman, Patrick E MacDonald and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.

0numbers the graph read from it
0cells of the map it votes in
148citing papers in PubMed
28.9field-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.

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

148 citing papers in PubMed, 247 citations in OpenAlex.

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  14. O-Acetyl-Serine Supplementation Enhances Insulin Secretion and Improves Postprandial Glycaemia in Lean and Prediabetic Mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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88 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

13 authors at 3 institutions in 2 countries.

Megan E CapozziDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Berit SvendsenDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Sara E EnciscoDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Sophie L LewandowskiDepartment of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Mackenzie D MartinDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Haopeng LinDepartment of Pharmacology and Alberta Diabetes Institute, University of Alberta, Alberta, Canada.
Justin L JaffeDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Reilly W CochDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Jonathan M HaldemanDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Patrick E MacDonaldDepartment of Pharmacology and Alberta Diabetes Institute, University of Alberta, Alberta, Canada.
Matthew J MerrinsDepartment of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Wisconsin-Madison, Madison, Wisconsin, USA.
David A D'AlessioDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Jonathan E CampbellDuke Molecular Physiology Institute, Duke University, Durham, North Carolina, USA.
Duke University · USUniversity of Alberta · CAUniversity of Wisconsin–Madison · US

Funding

PREDOCTORAL TRAINING IN MOLECULAR BIOPHYSICST32GM008293 · UNIVERSITY OF WISCONSIN MADISON · 1989 to 2005
$1.8M
Endocrinology and Metabolism Training ProgramT32DK007012 · DUKE UNIVERSITY · 1986 to 2025
$1.3M
Metabolic Functions of Pyruvate Kinase M2 in Pancreatic Beta-cellsR01DK113103 · UNIVERSITY OF WISCONSIN-MADISON · 2025 to 2025
$485k
NIA NIH HHS R21 AG050135NIDDK NIH HHS F32 DK116542NIDDK NIH HHS R01 DK101991NIDDK NIH HHS R01 DK113103NIDDK NIH HHS R01 DK123075NIDDK NIH HHS T32 DK007012NIGMS NIH HHS T32 GM008293
6 · The paper itself

Abstract

Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to β cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and nonmetabolic stimulation of mouse and human islets. This effect is due to reduced β cell cAMP and affects the quantity but not dynamics of insulin release, indicating that PGDPs dictate the magnitude of insulin output in an isolated islet. In healthy mice, additional factors that stimulate cAMP can compensate for loss of PGDP signaling; however, input from α cells is essential to maintain glucose tolerance during the metabolic stress induced by high-fat feeding. These findings demonstrate an essential role for α cell regulation of β cells, raising the possibility that abnormal paracrine signaling contributes to impaired insulin secretion in diabetes. Moreover, these findings support reconsideration of the role for α cells in postprandial glucose control.

Indexed as

Signal TransductionAnimalsCyclic AMPFemaleGastric Inhibitory PolypeptideGlucagon-Like Peptide 1Glucagon-Secreting CellsGlucoseHomeostasisHumansInsulinInsulin-Secreting CellsMaleMiceMice, Inbred C57BLProglucagonCyclic AMPGastric Inhibitory PolypeptideGlucagon-Like Peptide 1GlucoseInsulinProglucagonEndocrinologyG-protein coupled receptorsInsulinIslet cellsMetabolism

Identifiers

PMID30720465
PMCPMC6483521
OpenAlexW2914141586

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.