{
  "abstract": "Diabetes induces progressive transcriptional reprogramming in the heart and kidney, yet their tissue-specific temporal dynamics and cellular mechanisms remain incompletely understood. In this study, we employed a longitudinal design with dense sampling intervals, performing time-series bulk RNA-seq on heart and kidney tissues across six bi-weekly intervals from Control, high-fat diet (HF), diabetes (DM), and insulin-treated (INS) mice (n=38 total samples). To cross-validate and resolve cell-type-specific variations, these data were integrated with a public single-cell RNA-seq dataset (16 mouse kidneys) spanning Control, diabetic kidney disease (DKD), and SGLT2 inhibitor (SGLT2i) treatment groups. Principal component analysis and differential expression sequencing revealed a more pronounced, earlier transcriptional divergence in the kidney than in the heart under diabetic conditions. Using maSigPro regression analysis, we identified 74 core time-dependent genes in the kidney; hierarchical clustering showed that the major dynamic module was enriched in immunometabolic and inflammatory pathways. Single-cell dissection localized Enpp2 upregulation within injured proximal tubule cells (Inj.PT) of the DKD group, while MHC class I molecules (H2-K1 and H2-D1) were suppressed in immune cells. UpSet plot analysis demonstrated an overlap of these dynamic hub genes between bulk and single-cell cohorts. While insulin reversed systemic metabolic and early-phase immune aberrations in the bulk cohort, the single-cell dataset—derived from an independent SGLT2i-treated cohort—provided cellular resolution for key dynamic genes (Enpp2, H2-K1, H2-D1) and suggested that SGLT2i may similarly suppress Enpp2 in injured proximal tubule cells. These parallel observations from two distinct therapeutic interventions are hypothesis-generating and warrant direct comparative studies. These discovery-phase findings were validated by independent qPCR and immunohistochemical analyses. Taken together, this exploratory longitudinal analysis identifies tissue-specific temporal transcriptional reprogramming in diabetic heart and kidney, with evidence of partial modulation by insulin treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Endocrinology, The Second Affiliated Hospital of Zunyi Medical University",
    "Department of Biomedical Sciences, Faculty of Medicine, University of Macau",
    "Thyroid and Breast Surgery, the Second Affiliated Hospital of Zunyi Medical University",
    "Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shan-shan Gao"
    },
    {
      "affs": [
        1
      ],
      "name": "Guoyue Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jing An"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingmei Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Chuyu Liu"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Yulan Cai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0gbjat7z6k5jb.bib",
  "cited_by": 0,
  "doi": "10.3389/fendo.2026.1950040",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727396/?tool=EBI",
  "id": "0gbjat7z6k5jb",
  "issns": [
    "1664-2392"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1950040/full",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2727|Chronic Kidney Disease and Diabetes"
    ]
  ],
  "openalex": "W7223054922",
  "pdf_url": "https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2026.1950040/pdf",
  "pmcid": "PMC13727396",
  "pmid": "42978585",
  "published": "2026-10-20",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0gbjat7z6k5jb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:20Z",
      "native_id": "10.3389/fendo.2026.1950040",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fendo.2026.1950040/full"
    },
    {
      "first_seen": "2026-11-04T15:20:45Z",
      "native_id": "PMC:PMC13727396",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13727396"
    },
    {
      "first_seen": "2026-11-06T12:23:16Z",
      "native_id": "PMC13727396",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fendo.2026.1950040"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1664-2392",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Integrated time-series multi-omics reveals temporal reprogramming and inter-organ divergence in diabetic cardiorenal syndrome",
  "title_text": "Integrated time-series multi-omics reveals temporal reprogramming and inter-organ divergence in diabetic cardiorenal syndrome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:35Z",
  "url": "https://research.draconitic.com/paper/0gbjat7z6k5jb",
  "venue": "Frontiers in Endocrinology",
  "versions": []
}