Evidence map›Paper›PMID 36978133›Full record

ArticleCardiovascular diabetology2023

Aldose reductase inhibition alleviates diabetic cardiomyopathy and is associated with a decrease in myocardial fatty acid oxidation.

Keshav Gopal, Qutuba G Karwi, Seyed Amirhossein Tabatabaei Dakhili, Cory S Wagg, Liyan Zhang, Qiuyu Sun, Christina T Saed, Sai Panidarapu, Riccardo Perfetti, Ravichandran Ramasamy and 2 more

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

Article in Cardiovascular diabetology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
7.9field-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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. ExploringMolecules (Basel, Switzerland) · 2026
    Article
  4. Review
  5. Review
  6. Review
  7. Guidelines for diet-induced models of cardiometabolic syndrome.American journal of physiology. Heart and circulatory physiology · 2025
    Review
  8. Gut Microbiota-Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. TargetingFrontiers in bioinformatics · 2025
    Article
  15. Review
  16. Review
  17. Review
  18. MCU genetically altered mice suggest how mitochondrial CaTrends in endocrinology and metabolism: TEM · 2024
    Review
  19. Article
  20. Article
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

12 authors at 2 institutions in 2 countries.

Keshav GopalCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Qutuba G KarwiCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Seyed Amirhossein Tabatabaei DakhiliCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Cory S WaggCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Liyan ZhangCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Qiuyu SunCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Christina T SaedCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Sai PanidarapuCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Riccardo PerfettiApplied Therapeutics, New York, NY, USA.
Ravichandran RamasamyDiabetes Research Program, New York University Grossman Medical Center, New York, NY, USA.
John R UssherCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada.
Gary D LopaschukCardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada. gary.lopaschuk@ualberta.ca.
University of Alberta · CANew York University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCardiovascular diseases, including diabetic cardiomyopathy, are major causes of death in people with type 2 diabetes. Aldose reductase activity is enhanced in hyperglycemic conditions, leading to altered cardiac energy metabolism and deterioration of cardiac function with adverse remodeling. Because disturbances in cardiac energy metabolism can promote cardiac inefficiency, we hypothesized that aldose reductase inhibition may mitigate diabetic cardiomyopathy via normalization of cardiac energy metabolism.

methodsMale C57BL/6J mice (8-week-old) were subjected to experimental type 2 diabetes/diabetic cardiomyopathy (high-fat diet [60% kcal from lard] for 10 weeks with a single intraperitoneal injection of streptozotocin (75 mg/kg) at 4 weeks), following which animals were randomized to treatment with either vehicle or AT-001, a next-generation aldose reductase inhibitor (40 mg/kg/day) for 3 weeks. At study completion, hearts were perfused in the isolated working mode to assess energy metabolism.

resultsAldose reductase inhibition by AT-001 treatment improved diastolic function and cardiac efficiency in mice subjected to experimental type 2 diabetes. This attenuation of diabetic cardiomyopathy was associated with decreased myocardial fatty acid oxidation rates (1.15 ± 0.19 vs 0.5 ± 0.1 µmol min

conclusionsInhibiting aldose reductase activity ameliorates diastolic dysfunction in mice with experimental type 2 diabetes, which may be due to the decline in myocardial fatty acid oxidation, indicating that treatment with AT-001 may be a novel approach to alleviate diabetic cardiomyopathy in patients with diabetes.

Indexed as

Diabetes Mellitus, Type 2Diabetic CardiomyopathiesAldehyde ReductaseAnimalsBenzothiazolesDisease Models, AnimalFatty AcidsMaleMiceMice, Inbred C57BLMyocardiumPyrazinesPyridonesRandom AllocationAldehyde ReductaseBenzothiazolescaficrestatFatty AcidsPyrazinesPyridonesAldose reductaseAT-001Diabetic cardiomyopathyDiastolic dysfunctionFatty acid oxidation

Identifiers

PMID36978133
PMCPMC10053619
OpenAlexW4361211770

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.