{
  "abstract": "Abnormal myocardial fuel utilization contributes to heart failure (HF). Myocardial glucose uptake in response to insulin is suppressed in patients with HF, but the mechanisms of this metabolic inflexibility are not fully understood. The present studies employ culture surfaces with tunable stiffness, quantitatively mimicking the healthy and diseased heart milieu. We observe that human and rat adult cardiomyocytes cultured on stiff surfaces develop blunted insulin-mediated glucose uptake, associated with intracellular aggregation of the high-affinity glucose transporter GLUT4 within the microtubule network, and with impaired contractility. These effects are prevented by blocking stiffness-induced detyrosination of α-tubulin, and can be partially rescued by metformin, through AMPK activation. Similarly, disabling motor proteins that mediate microtubule-based trafficking of GLUT4 independently alter insulin-mediated glucose uptake and contractility in myocytes. These findings demonstrate a cell-autonomous mechanism of stiffness-induced impairment of GLUT4 trafficking and glucose uptake in adult rat and human cardiomyocytes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine and Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA",
    "Department of Pediatrics, Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA",
    "Department of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA",
    "Lead Contact"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alexia Vite"
    },
    {
      "affs": [
        0
      ],
      "name": "Tony Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Nesrine Bouhrira"
    },
    {
      "affs": [
        0
      ],
      "name": "Deborah M. Eaton"
    },
    {
      "affs": [
        0
      ],
      "name": "Kenneth C. Bedi"
    },
    {
      "affs": [
        0
      ],
      "name": "Claire F. Brady"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jonathan J. Edwards"
    },
    {
      "affs": [
        0
      ],
      "name": "Bea Duric"
    },
    {
      "affs": [
        2
      ],
      "name": "Keita Uchida"
    },
    {
      "affs": [
        0
      ],
      "name": "Cassidy Olsen"
    },
    {
      "affs": [
        0
      ],
      "name": "Lola Dong"
    },
    {
      "affs": [
        2
      ],
      "name": "Benjamin L. Prosser"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Zoltan Arany"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Kenneth B. Margulies"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cxkpf9v5nee29.bib",
  "cited_by": 2,
  "doi": "10.1016/j.celrep.2026.117577",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13729075/",
  "id": "cxkpf9v5nee29",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://doi.org/10.1016/j.celrep.2026.117577",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1307|Cellular Mechanics and Interactions"
    ]
  ],
  "openalex": "W7165541757",
  "pdf_url": null,
  "pmcid": "PMC13729075",
  "pmid": "42329768",
  "published": "2026-06-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cxkpf9v5nee29.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:21:54Z",
      "native_id": "PMC13729075",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.celrep.2026.117577"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Cellular Mechanics and Interactions",
      "subfield": "cell-biology"
    }
  ],
  "title": "Stiffness-Induced Impairment of GLUT4 Trafficking in Adult Cardiomyocytes",
  "title_text": "Stiffness-Induced Impairment of GLUT4 Trafficking in Adult Cardiomyocytes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:54Z",
  "url": "https://research.draconitic.com/paper/cxkpf9v5nee29",
  "venue": "Cell reports",
  "versions": []
}