{
  "abstract": "Intracellular Ca 2+ signaling is essential for glucose-induced insulin secretion (GIIS) and hepatic glucose production (HGP), yet how Ca 2+ dynamics are coordinated across organs remains unclear. Carbonic anhydrase VIII (CA8), an endogenous inhibitor of inositol 1,4,5-trisphosphate receptor 1 (IP3R1), was identified as a shared regulator of pancreatic and hepatic glucose metabolism. Using Car8 wdl mice, we showed that CA8 deficiency enhanced GIIS and HGP in vivo and ex vivo. In islets and hepatocytes, CA8 loss augments Ca 2+ oscillations, an effect abolished by IP3R inhibition or Car8 reexpression. Enhanced HGP persists independently of glucagon receptor, PLC, or PKA signaling and occurs without increased IP 1 , indicating heightened IP3R1 sensitivity rather than increased IP 3 production. In hepatocytes, chronic glucagon exposure attenuated acute glucagon responsiveness in a CA8-dependent manner. In obese diabetic mice, CA8 increased in islets but decreased in hepatocytes; hepatic CA8 restoration reduced excessive HGP. Collectively, these findings identify CA8 as a cross-organ regulator of IP3R1-dependent Ca 2+ signaling with translational relevance to diabetes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Diabetes, Endocrinology, and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan.",
    "Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.",
    "Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan.",
    "Department of Diabetes, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.",
    "Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.",
    "Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai, Osaka, Japan."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Muhammad Fauzi",
      "orcid": "0000-0001-9097-3938"
    },
    {
      "affs": [
        0
      ],
      "name": "Takaaki Murakami",
      "orcid": "0000-0003-3844-1138"
    },
    {
      "affs": [
        1
      ],
      "name": "Ryota Usui"
    },
    {
      "affs": [
        0
      ],
      "name": "Ainur Botagarova",
      "orcid": "0000-0001-5610-4659"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Otani",
      "orcid": "0009-0000-8185-673X"
    },
    {
      "affs": [
        0
      ],
      "name": "Kentarou Sakaki",
      "orcid": "0009-0003-3690-102X"
    },
    {
      "affs": [
        0
      ],
      "name": "Shinsuke Tokumoto",
      "orcid": "0000-0002-4070-6724"
    },
    {
      "affs": [
        0
      ],
      "name": "Toshinori Imaizumi",
      "orcid": "0000-0001-8808-1893"
    },
    {
      "affs": [
        2
      ],
      "name": "Hisato Tatsuoka"
    },
    {
      "affs": [
        3
      ],
      "name": "Masahito Ogura",
      "orcid": "0000-0002-7107-2752"
    },
    {
      "affs": [
        4
      ],
      "name": "Jonathan Campbell",
      "orcid": "0000-0003-4358-6331"
    },
    {
      "affs": [
        5
      ],
      "name": "Nobuya Inagaki"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Yabe",
      "orcid": "0000-0002-5334-7687"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ab6q2mnat8myj.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeh4948",
  "fulltext_url": null,
  "id": "ab6q2mnat8myj",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aeh4948",
  "language": null,
  "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": [
    [
      "openalex",
      "2746|Pancreatic function and diabetes"
    ]
  ],
  "openalex": "W7221070852",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/ab6q2mnat8myj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aeh4948",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aeh4948"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Pancreatic function and diabetes",
      "subfield": "surgery"
    }
  ],
  "title": "Carbonic anhydrase VIII regulates IP3R1-dependent Ca ²⁺ signaling to coordinate insulin secretion and hepatic glucose production",
  "title_text": "Carbonic anhydrase VIII regulates IP3R1-dependent Ca ²⁺ signaling to coordinate insulin secretion and hepatic glucose production",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:41Z",
  "url": "https://research.draconitic.com/paper/ab6q2mnat8myj",
  "venue": "Science Advances",
  "versions": []
}