Evidence map›Paper›PMID 33168621›Full record

ArticleDiabetes2021

Pancreatic β-Cell-Specific Deletion of VPS41 Causes Diabetes Due to Defects in Insulin Secretion.

Christian H Burns, Belinda Yau, Anjelica Rodriguez, Jenna Triplett, Drew Maslar, You Sun An, Reini E N van der Welle, Ross G Kossina, Max R Fisher, Gregory W Strout and 7 more

Open access · greenAbstract read
In one paragraph

Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. EccDNA-Driven VPS41 Amplification Alleviates Genotoxic Stress via Lysosomal KAI1 Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  3. Article
  4. Review
  5. Genetics and diet shape the relationship between islet function and whole body metabolism.American journal of physiology. Endocrinology and metabolism · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 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

17 authors at 5 institutions in 4 countries.

Christian H BurnsDepartment of Biological Sciences, University of Denver, Denver, CO.
Belinda YauDiscipline of Physiology, School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia.
Anjelica RodriguezDepartment of Biological Sciences, University of Denver, Denver, CO.
Jenna TriplettDepartment of Biological Sciences, University of Denver, Denver, CO.
Drew MaslarDepartment of Biological Sciences, University of Denver, Denver, CO.
You Sun AnDiscipline of Physiology, School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia.
Reini E N van der WelleSection of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Ross G KossinaWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO.
Max R FisherWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO.
Gregory W StroutWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO.
Peter O BayguinovWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO.
Tineke VeenendaalSection of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
David ChitayatDivision of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
James A J FitzpatrickWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO.
Judith KlumpermanSection of Cell Biology, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Melkam A KebedeDiscipline of Physiology, School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia.
Cedric S AsensioDepartment of Biological Sciences, University of Denver, Denver, CO cedric.asensio@du.edu.ORCID 0000-0002-2284-0217
University of Denver · USWashington University in St. Louis · USThe University of Sydney · AUUtrecht University · NLUniversity of Toronto · CA

Funding

WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Formation of the Regulated Secretory Pathway: a View from the CytosolR01GM124035 · NIGMS · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI ASENSIO, CEDRIC STEPHANE · 2017 to 2021
$1.5M
Cellular Mechanisms Controlling the Formation of Large Dense Core VesiclesR15GM116096 · NIGMS · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI ASENSIO, CEDRIC STEPHANE · 2015 to 2015
$360k
NIDDK NIH HHS P30 DK020579NIGMS NIH HHS R01 GM124035NIGMS NIH HHS R15 GM116096
6 · The paper itself

Abstract

Insulin secretory granules (SGs) mediate the regulated secretion of insulin, which is essential for glucose homeostasis. The basic machinery responsible for this regulated exocytosis consists of specific proteins present both at the plasma membrane and on insulin SGs. The protein composition of insulin SGs thus dictates their release properties, yet the mechanisms controlling insulin SG formation, which determine this molecular composition, remain poorly understood. VPS41, a component of the endolysosomal tethering homotypic fusion and vacuole protein sorting (HOPS) complex, was recently identified as a cytosolic factor involved in the formation of neuroendocrine and neuronal granules. We now find that VPS41 is required for insulin SG biogenesis and regulated insulin secretion. Loss of VPS41 in pancreatic β-cells leads to a reduction in insulin SG number, changes in their transmembrane protein composition, and defects in granule-regulated exocytosis. Exploring a human point mutation, identified in patients with neurological but no endocrine defects, we show that the effect on SG formation is independent of HOPS complex formation. Finally, we report that mice with a deletion of VPS41 specifically in β-cells develop diabetes due to severe depletion of insulin SG content and a defect in insulin secretion. In sum, our data demonstrate that VPS41 contributes to glucose homeostasis and metabolism.

Indexed as

AnimalsCell LineDiabetes MellitusExocytosisGlucose Tolerance TestInsulin-Secreting CellsInsulin SecretionMiceMice, KnockoutRatsSecretory VesiclesVesicular Transport ProteinsVesicular Transport ProteinsVps41 protein, mouse

Identifiers

PMID33168621
PMCPMC7881869
OpenAlexW3101927480

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.