Evidence map›Paper›PMID 32352931›Full record

ArticleJCI insight2020

Integrated human pseudoislet system and microfluidic platform demonstrate differences in GPCR signaling in islet cells.

John T Walker, Rachana Haliyur, Heather A Nelson, Matthew Ishahak, Gregory Poffenberger, Radhika Aramandla, Conrad Reihsmann, Joseph R Luchsinger, Diane C Saunders, Peng Wang and 5 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
7.6field-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

37 citing papers in PubMed, 54 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

15 authors at 5 institutions in 1 country.

John T WalkerDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Rachana HaliyurDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Heather A NelsonDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Matthew IshahakDepartment of Biomedical Engineering, University of Miami, Miami, Florida, USA.
Gregory PoffenbergerDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Radhika AramandlaDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Conrad ReihsmannDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Joseph R LuchsingerVanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Diane C SaundersDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Peng WangDiabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Adolfo Garcia-OcañaDiabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Rita BottinoInstitute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.
Ashutosh AgarwalDepartment of Biomedical Engineering, University of Miami, Miami, Florida, USA.
Alvin C PowersDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Marcela BrissovaDivision of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vanderbilt University Medical Center · USVanderbilt University · USIcahn School of Medicine at Mount Sinai · USUniversity of Miami · USAllegheny Health Network · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI JEFFREY E. PESSIN · 2015 to 2026
$27.7M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
The Human Islet Distribution Coordinating Center (UC4)UC4DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI EVANS-MOLINA, CARMELLA, NILAND, JOYCE CAROL · 2012 to 2017
$25.6M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
Integrated Islet Distribution Program (U24) - 2021U24DK098085 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI Carmella Evans-Molina, Joyce Carol Niland · 2021 to 2026
$17.8M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Supplement to Integrated Program for Human Pancreas Procurement and AnalysisUC4DK112232 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ATKINSON, MARK A., POWERS, ALVIN C · 2016 to 2020
$8.4M
Discovery of Pancreatic Signatures in Type 2 Diabetes MellitusR24DK106755 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAI, LONG, CAPRIOLI, RICHARD M · 2015 to 2019
$6.2M
Engineering a Human Physiomimetic Islet MicrosystemUC4DK104208 · NIDDK · UNIVERSITY OF FLORIDA · PI AGARWAL, ASHUTOSH, RICORDI, CAMILLO · 2014 to 2014
$4.9M
BLRD VA I01 BX000666NCI NIH HHS P30 CA068485NEI NIH HHS P30 EY008126NIAAA NIH HHS F30 AA027126NIDDK NIH HHS F30 DK112630NIDDK NIH HHS F30 DK118830NIDDK NIH HHS F31 DK118860NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK094199NIDDK NIH HHS R01 DK117147NIDDK NIH HHS R24 DK106755NIDDK NIH HHS U01 DK120456NIDDK NIH HHS U24 DK059637NIDDK NIH HHS U24 DK098085NIDDK NIH HHS UC4 DK098085NIDDK NIH HHS UC4 DK104208NIDDK NIH HHS UC4 DK104211NIDDK NIH HHS UC4 DK108120NIDDK NIH HHS UC4 DK112232NIDDK NIH HHS UG3 DK122638NIDDK NIH HHS UH3 DK122638NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM152284NIH HHS S10 OD021630
6 · The paper itself

Abstract

Pancreatic islets secrete insulin from β cells and glucagon from α cells, and dysregulated secretion of these hormones is a central component of diabetes. Thus, an improved understanding of the pathways governing coordinated β and α cell hormone secretion will provide insight into islet dysfunction in diabetes. However, the 3D multicellular islet architecture, essential for coordinated islet function, presents experimental challenges for mechanistic studies of intracellular signaling pathways in primary islet cells. Here, we developed an integrated approach to study the function of primary human islet cells using genetically modified pseudoislets that resemble native islets across multiple parameters. Further, we developed a microperifusion system that allowed synchronous acquisition of GCaMP6f biosensor signal and hormone secretory profiles. We demonstrate the utility of this experimental approach by studying the effects of Gi and Gq GPCR pathways on insulin and glucagon secretion by expressing the designer receptors exclusively activated by designer drugs (DREADDs) hM4Di or hM3Dq. Activation of Gi signaling reduced insulin and glucagon secretion, while activation of Gq signaling stimulated glucagon secretion but had both stimulatory and inhibitory effects on insulin secretion, which occur through changes in intracellular Ca2+. The experimental approach of combining pseudoislets with a microfluidic system allowed the coregistration of intracellular signaling dynamics and hormone secretion and demonstrated differences in GPCR signaling pathways between human β and α cells.

Indexed as

Biosensing TechniquesLab-On-A-Chip DevicesMicrofluidic Analytical TechniquesSignal TransductionFemaleGlucagon-Secreting CellsHumansInsulin-Secreting CellsInsulin SecretionMaleReceptors, G-Protein-CoupledReceptors, G-Protein-CoupledDiabetesEndocrinologyIslet cellsMetabolism

Identifiers

PMID32352931
PMCPMC7259531
OpenAlexW3022277769

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.