Evidence map›Paper›PMID 27408771›Full record

ArticleMolecular metabolism2016

Comprehensive alpha, beta and delta cell transcriptomes reveal that ghrelin selectively activates delta cells and promotes somatostatin release from pancreatic islets.

Michael R DiGruccio, Alex M Mawla, Cynthia J Donaldson, Glyn M Noguchi, Joan Vaughan, Christopher Cowing-Zitron, Talitha van der Meulen, Mark O Huising

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed
29.8field-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.

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

228 citing papers in PubMed, 336 citations in OpenAlex.

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  19. Glycolytic activation of β-cell NaMolecular metabolism · 2026
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168 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

8 authors at 3 institutions in 2 countries.

Michael R DiGruccioDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA. Electronic address: mrdigruccio@ucdavis.edu.
Alex M MawlaDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA. Electronic address: ammawla@ucdavis.edu.
Cynthia J DonaldsonClayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines road, La Jolla, CA, USA. Electronic address: donaldson@salk.edu.
Glyn M NoguchiDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA. Electronic address: gmnoguchi@ucdavis.edu.
Joan VaughanClayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, 10010 North Torrey Pines road, La Jolla, CA, USA. Electronic address: vaughan@salk.edu.
Christopher Cowing-ZitronDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA.
Talitha van der MeulenDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA. Electronic address: tvandermeulen@ucdavis.edu.
Mark O HuisingDepartment of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, One Shields Avenue, 196 Briggs Hall, Davis, CA, USA. Electronic address: mhuising@ucdavis.edu.
University of California, Davis · USSalk Institute for Biological Studies · USUniversity of California System · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveComplex local crosstalk amongst endocrine cells within the islet ensures tight coordination of their endocrine output. This is illustrated by the recent demonstration that the negative feedback control by delta cells within pancreatic islets determines the homeostatic set-point for plasma glucose during mouse postnatal development. However, the close association of islet endocrine cells that facilitates paracrine crosstalk also complicates the distinction between effects mediated directly on beta cells from indirect effects mediated via local intermediates, such as somatostatin from delta cells.

methodsTo resolve this problem, we generated reporter mice that allow collection of pure pancreatic delta cells along with alpha and beta cells from the same islets and generated comprehensive transcriptomes for each islet endocrine cell type. These transcriptomes afford an unparalleled view of the receptors expressed by delta, alpha and beta cells, and allow the prediction of which signal targets which endocrine cell type with great accuracy.

resultsFrom these transcriptomes, we discovered that the ghrelin receptor is expressed exclusively by delta cells within the islet, which was confirmed by fluorescent in situ hybridization and qPCR. Indeed, ghrelin increases intracellular calcium in delta cells in intact mouse islets, measured by GCaMP6 and robustly potentiates glucose-stimulated somatostatin secretion on mouse and human islets in both static and perfusion assays. In contrast, des-acyl-ghrelin at the same dose had no effect on somatostatin secretion and did not block the actions of ghrelin.

conclusionsThese results offer a straightforward explanation for the well-known insulinostatic actions of ghrelin. Rather than engaging beta cells directly, ghrelin engages delta cells to promote local inhibitory feedback that attenuates insulin release. These findings illustrate the power of our approach to resolve some of the long-standing conundrums with regard to the rich feedback that occurs within the islet that is integral to islet physiology and therefore highly relevant to diabetes.

Indexed as

Alpha cellBeta cellCrhr2, Corticotropin-releasing hormone receptor type 2Delta cellFISH, Fluorescent in situ hybridizationGhrelinGhsr, Growth hormone secretagogue receptorGSSS, Glucose-stimulated somatostatin secretionIapp, Islet amyloid polypeptideRPKM, Reads per kilobase gene model per million reads sequencedSomatostatin releaseTranscriptomeTrpm2, Transient receptor potential melastatin 2Ucn3, Urocortin 3YFP, Yellow fluorescent protein

Identifiers

PMID27408771
PMCPMC4921781
OpenAlexW2346764160

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.