Evidence map›Paper›PMID 41023280›Full record

ArticleNature cardiovascular research2025

Targeted glycophagy ATG8 therapy reverses diabetic heart disease in mice and in human engineered cardiac tissues.

K M Mellor, U Varma, P Koutsifeli, C L Curl, J V Janssens, L J Daniels, G B Bernasochi, A J A Raaijmakers, M Annandale, X Li and 16 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

K M MellorDepartment of Physiology, University of Auckland, Auckland, New Zealand.ORCID http://orcid.org/0000-0002-8443-9365
U VarmaDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
P KoutsifeliDepartment of Physiology, University of Auckland, Auckland, New Zealand.
C L CurlDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
J V JanssensDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
L J DanielsDepartment of Physiology, University of Auckland, Auckland, New Zealand.
G B BernasochiDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
A J A RaaijmakersDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
M AnnandaleDepartment of Physiology, University of Auckland, Auckland, New Zealand.
X LiDepartment of Physiology, University of Auckland, Auckland, New Zealand.
S L JamesDepartment of Physiology, University of Auckland, Auckland, New Zealand.
D J TaylorCedars-Sinai Medical Center, Los Angeles, CA, USA.
K RaedscheldersCedars-Sinai Medical Center, Los Angeles, CA, USA.
K L WeeksDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
R J MillsMurdoch Children's Research Institute, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-9735-2595
R G PartonCentre for Microscopy and Microanalysis and Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-7494-5248
X HuInstitute of Molecular Medicine, Peking University, Beijing, China.ORCID http://orcid.org/0000-0003-4911-5354
J R BellDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.
T J O'BrienDepartment of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
R KatareDepartment of Physiology, HeartOtago, University of Otago, Dunedin, New Zealand.ORCID http://orcid.org/0000-0001-5419-7935
E R PorrelloDepartment of Anatomy and Physiology, University of Melbourne, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-6105-7463
J E HudsonSchool of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0003-0832-9356
R P XiaoInstitute of Molecular Medicine, Peking University, Beijing, China.ORCID http://orcid.org/0000-0003-2448-409X
J E Van EykCedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-9050-148X
R A GottliebCedars-Sinai Medical Center, Los Angeles, CA, USA.
L M D DelbridgeDepartment of Physiology, University of Auckland, Auckland, New Zealand. lmd@unimelb.edu.au.ORCID http://orcid.org/0000-0003-1859-0152

Funding

Department of Health | National Health and Medical Research Council (NHMRC) 1027865, 628643, 1082215, 1037320, 1067869, 1157320Manatu Hauora | Health Research Council of New Zealand (HRC) 19/190U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01 HL144509-01
6 · The paper itself

Abstract

Diabetic heart disease is highly prevalent and is associated with the early development of impaired diastolic relaxation. The mechanisms of diabetic heart disease are poorly understood, and it is a condition for which there are no targeted therapies. Recently, disrupted glycogen autophagy (glycophagy) and glycogen accumulation have been identified in the diabetic heart. Glycophagy involves glycogen receptor binding and linking with an ATG8 protein to locate and degrade glycogen within an intracellular phagolysosome. Here we show that glycogen receptor protein starch binding domain protein 1 (STBD1) is mobilized early in the cardiac glycogen response to metabolic challenge in vivo, and that deficiency of a specific ATG8 family protein, γ-aminobutyric acid type A receptor-associated protein-like 1 (GABARAPL1), is associated with diastolic dysfunction in diabetes. Gabarapl1 gene delivery treatment remediated cardiomyocyte and cardiac diastolic dysfunction in type 2 diabetic mice and the diastolic performance of 'diabetic' human induced pluripotent stem cell-derived cardiac organoids. We identify glycophagy dysregulation as a mechanism and potential treatment target for diabetic heart disease.

Indexed as

AutophagyAutophagy-Related Protein 8 FamilyDiabetes Mellitus, Type 2Diabetic CardiomyopathiesGenetic TherapyGlycogenMicrotubule-Associated ProteinsMyocytes, CardiacTissue EngineeringAdaptor Proteins, Signal TransducingAnimalsDiabetes Mellitus, ExperimentalDisease Models, AnimalHumansInduced Pluripotent Stem CellsMaleAdaptor Proteins, Signal TransducingAutophagy-Related Protein 8 FamilyGABARAPL1 protein, humanGlycogenMicrotubule-Associated Proteins

Identifiers

PMID41023280

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.