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The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes

Author

Listed:
  • Rachel J. Perry

    (Yale University School of Medicine)

  • Varman T. Samuel

    (Yale University School of Medicine
    VA Connecticut Healthcare System West Haven)

  • Kitt F. Petersen

    (Yale University School of Medicine
    Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen)

  • Gerald I. Shulman

    (Yale University School of Medicine
    Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
    Yale University School of Medicine
    Howard Hughes Medical Institute, Yale University School of Medicine)

Abstract

Non-alcoholic fatty liver disease and its downstream sequelae, hepatic insulin resistance and type 2 diabetes, are rapidly growing epidemics, which lead to increased morbidity and mortality rates, and soaring health-care costs. Developing interventions requires a comprehensive understanding of the mechanisms by which excess hepatic lipid develops and causes hepatic insulin resistance and type 2 diabetes. Proposed mechanisms implicate various lipid species, inflammatory signalling and other cellular modifications. Studies in mice and humans have elucidated a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance. Therapeutic approaches based on this mechanism could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.

Suggested Citation

  • Rachel J. Perry & Varman T. Samuel & Kitt F. Petersen & Gerald I. Shulman, 2014. "The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes," Nature, Nature, vol. 510(7503), pages 84-91, June.
    • Handle: RePEc:nat:nature:v:510:y:2014:i:7503:d:10.1038_nature13478
    DOI: 10.1038/nature13478
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    Cited by:

    1. Anna Worthmann & Julius Ridder & Sharlaine Y. L. Piel & Ioannis Evangelakos & Melina Musfeldt & Hannah Voß & Marie O’Farrell & Alexander W. Fischer & Sangeeta Adak & Monica Sundd & Hasibullah Siffeti , 2024. "Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Oriol Juanola & Sebastián Martínez-López & Rubén Francés & Isabel Gómez-Hurtado, 2021. "Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors," IJERPH, MDPI, vol. 18(10), pages 1-24, May.
    3. Liu, Pengqiang & Li, Xin & Chang, Hsu-Ling & Su, Nan, 2024. "Natural resources Kuznets curve: The role of mineral resources, urbanization, and digitalization in BRICS economies," Resources Policy, Elsevier, vol. 90(C).

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