{
  "abstract": "Insulin is a central regulator of metabolic homoeostasis with diverse, tissue-specific actions across multiple organs. Despite major advances in insulin formulations, current therapies rely on systemic delivery and do not reproduce the physiological distribution of endogenous insulin, resulting in non-physiological tissue exposure and associated metabolic limitations. In this perspective, we discuss emerging strategies aimed at achieving tissue-selective insulin action, including molecular engineering of insulin analogues, modulation of insulin receptor isoform specificity and targeted delivery approaches. Attention is given to hepato-preferential, muscle-directed, brain-targeted and adipose-modulating strategies, highlighting their mechanistic basis, therapeutic potential and inherent limitations. While proof of principle has been established for several approaches, challenges remain in balancing tissue selectivity with whole-body metabolic control. Advances in protein design and delivery technologies may ultimately enable the development of next-generation insulin therapies that better mimic physiological insulin action and improve clinical outcomes in metabolic and neurodegenerative diseases.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences 1 , Prague, Czech Republic",
    "Department of Biochemistry, Faculty of Science, Charles University 2 , Prague, Czech Republic"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Maxmilián Hejl",
      "orcid": "0009-0000-3043-0165"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiří Jiráček",
      "orcid": "0000-0003-3848-2773"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1txbk6j1zq775.bib",
  "cited_by": 0,
  "doi": "10.1098/rsob.260175",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13716293/",
  "id": "1txbk6j1zq775",
  "issns": [
    "2046-2441"
  ],
  "landing_url": "https://royalsocietypublishing.org/rsob/article/16/10/260175/483582/Perspectives-on-tissue-selective-insulin",
  "language": "en",
  "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",
      "Biochemistry"
    ],
    [
      "heading",
      "Biotechnology"
    ],
    [
      "heading",
      "Cellular Biology"
    ],
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2712|Diabetes Management and Research"
    ]
  ],
  "openalex": "W7221676236",
  "pdf_url": "https://royalsocietypublishing.org/rsob/article-pdf/doi/10.1098/rsob.260175/6169739/rsob.260175.pdf",
  "pmcid": "PMC13716293",
  "pmid": "42869456",
  "published": "2026-10-07",
  "publisher": "The Royal Society",
  "ris": "https://research.draconitic.com/paper/1txbk6j1zq775.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:04Z",
      "native_id": "10.1098/rsob.260175",
      "source": "crossref",
      "url": "https://royalsocietypublishing.org/rsob/article/16/10/260175/483582/Perspectives-on-tissue-selective-insulin"
    },
    {
      "first_seen": "2026-11-01T12:23:19Z",
      "native_id": "PMC13716293",
      "source": "pmc",
      "url": "https://doi.org/10.1098/rsob.260175"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "heading:Biochemistry",
      "subfield": "general"
    },
    {
      "field": "biology",
      "origin": "heading:Biotechnology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Perspectives on tissue-selective insulin derivatives",
  "title_text": "Perspectives on tissue-selective insulin derivatives",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:19Z",
  "url": "https://research.draconitic.com/paper/1txbk6j1zq775",
  "venue": "Open Biology",
  "versions": []
}