{
  "abstract": "Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the functional von Hippel–Lindau (VHL) complex and distinctive clear cell morphology associated with intracellular glycogen and lipid accumulation. However, the mechanism underlying glycogen storage remains unclear. This study was conducted to investigate the relationship between SGLT2, a glucose transporter predominantly expressed in proximal tubular epithelial cells; the cell of origin of ccRCC; and clear cell morphology in ccRCC. Using the VHL-null ccRCC cell line KMRC-1, we investigated the effects of the SGLT2 inhibitor dapagliflozin, SGLT2 knockdown, and VHL overexpression on cellular morphology, intracellular glycogen accumulation, and glucose uptake. Immunohistochemical expression of SGLT2, glucose transporter 1, and VHL was evaluated in morphologically heterogeneous ccRCC specimens. Periodic acid–Schiff (PAS) and PAS with diastase staining, together with quantitative image analysis of PAS-stained cells, showed that dapagliflozin treatment, SGLT2 knockdown, and VHL restoration reduced cytoplasmic area and cytoplasmic PAS staining intensity in KMRC-1 cells. In the fluorescent glucose uptake assay, dapagliflozin significantly reduced the fluorescence signal (p < 0.05). In paired intratumoral analyses of six VHL-deficient ccRCC specimens, SGLT2 immunohistochemical scores were significantly higher in clear cell components than in eosinophilic components (p = 0.026), whereas GLUT1 scores did not differ significantly (p = 0.850). These findings suggest that SGLT2-mediated glucose uptake contributes to glycogen accumulation and the glycogen-rich clear cell morphology of VHL-deficient ccRCC. The potential therapeutic relevance of SGLT2 inhibition in ccRCC warrants further investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan",
    "Department of Urology, Shimane University Faculty of Medicine, Izumo 693-8501, Shimane, Japan",
    "Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan",
    "Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Fukuoka, Japan",
    "Department of Urology, Kurate Hospital, Kurate 807-1311, Fukuoka, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Yujiro Nagata",
      "orcid": "0000-0001-6815-4266"
    },
    {
      "affs": [
        0
      ],
      "name": "Ikko Tomisaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Takuo Matsukawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Nguyen Thu Quynh",
      "orcid": "0000-0001-7468-9718"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuto Tsubonuma"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshihiro Sugita"
    },
    {
      "affs": [
        2
      ],
      "name": "Aya Nawata",
      "orcid": "0000-0002-7871-2425"
    },
    {
      "affs": [
        3
      ],
      "name": "Keiji Kokubu",
      "orcid": "0000-0001-6803-9321"
    },
    {
      "affs": [
        3
      ],
      "name": "Ryoko Baba",
      "orcid": "0000-0002-6071-7930"
    },
    {
      "affs": [
        3
      ],
      "name": "Hiroyuki Morimoto"
    },
    {
      "affs": [
        1
      ],
      "name": "Kohei Ogawa",
      "orcid": "0000-0002-0924-2669"
    },
    {
      "affs": [
        1
      ],
      "name": "Koichiro Wada"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Naohiro Fujimoto",
      "orcid": "0000-0002-5256-6415"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bsj241j81t94n.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209128",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705306/?tool=EBI",
  "id": "bsj241j81t94n",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9128",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Renal cell carcinoma treatment"
    ]
  ],
  "openalex": "W7221870862",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13705306/pdf/?tool=EBI",
  "pmcid": "PMC13705306",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/bsj241j81t94n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27209128",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9128"
    },
    {
      "first_seen": "2026-10-30T12:21:31Z",
      "native_id": "PMC:PMC13705306",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13705306"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Renal cell carcinoma treatment",
      "subfield": "general"
    }
  ],
  "title": "Sodium–Glucose Cotransporter 2-Mediated Glucose Uptake Contributes to Glycogen Accumulation in Clear Cell Renal Cell Carcinoma: Implications for Clear Cell Morphology and Potential Therapeutic Relevance",
  "title_text": "Sodium–Glucose Cotransporter 2-Mediated Glucose Uptake Contributes to Glycogen Accumulation in Clear Cell Renal Cell Carcinoma: Implications for Clear Cell Morphology and Potential Therapeutic Relevance",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:31Z",
  "url": "https://research.draconitic.com/paper/bsj241j81t94n",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}