Evidence map›Paper›PMID 37891673›Full record

ArticleCardiovascular diabetology2023

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

Yu-Han Chen, Albert P Ta, Yumay Chen, Hsiao-Chen Lee, Wenjun Fan, Phang-Lang Chen, Maria C Jordan, Kenneth P Roos, Grant R MacGregor, Qin Yang and 3 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 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. 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
  7. Review
  8. Article
  9. [Regulatory Role of the AKT1/AMPK Pathway in Oxidative Stress of Lens Epithelial Cells in Cataract Patients].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025
    Article
  10. Article
  11. 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

13 authors at 4 institutions in 2 countries.

Yu-Han Chen *Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Room 1011, Gonda South Rm 1011, 1500 E. Duarte Rd., Duarte, CA, 91010-3000, USA.
Albert P Ta *Department of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Room 1011, Gonda South Rm 1011, 1500 E. Duarte Rd., Duarte, CA, 91010-3000, USA.
Yumay ChenDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Hsiao-Chen LeeDepartment of Medicine, University of California Irvine, Irvine, CA, USA.
Wenjun FanDepartment of Medicine, University of California Irvine, Irvine, CA, USA.
Phang-Lang ChenDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Maria C JordanDepartment of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Kenneth P RoosDepartment of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Grant R MacGregorDepartment of Developmental and Cell Biology, University of California Irvine, Irvine, CA, USA.
Qin YangDepartment of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
Robert A EdwardsDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA, USA.
Junfeng LiDepartment of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Room 1011, Gonda South Rm 1011, 1500 E. Duarte Rd., Duarte, CA, 91010-3000, USA.
Ping H WangDepartment of Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Room 1011, Gonda South Rm 1011, 1500 E. Duarte Rd., Duarte, CA, 91010-3000, USA. pwang@coh.org.
City Of Hope National Medical Center · USUniversity of California, Irvine · USUniversity of California, Los Angeles · USKaohsiung Medical University · TW

Funding

Insulin's Control of Myocardial Mitochondria Bioenergetics and BiogenesisR01HL096987 · NHLBI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WANG, PING H · 2010 to 2013
$1.5M
NHLBI NIH HHS R01 HL096987NIH HHS R01HL096987
6 · The paper itself

Abstract

backgroundThe PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation.

methodsTo focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart.

resultsUpon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver.

conclusionCAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

Indexed as

Diabetes MellitusDiabetic CardiomyopathiesProto-Oncogene Proteins c-aktAdenosine TriphosphateAnimalsEnergy MetabolismInsulinMiceMice, TransgenicMitochondria, HeartMyocardiumPhosphatidylinositol 3-KinasesAdenosine TriphosphateInsulinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktATP synthaseDiabetic cardiomyopathyFatty liverHeart failureMitochondria dysfunctionMitochondrial AKTObesity

Identifiers

PMID37891673
PMCPMC10612246
OpenAlexW4387969806

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.