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The integrative biology of type 2 diabetes

Author

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  • Michael Roden

    (Medical Faculty, Heinrich-Heine University
    Leibniz Center for Diabetes Research at Heinrich-Heine University
    German Center for Diabetes Research, Partner Düsseldorf)

  • Gerald I. Shulman

    (Yale School of Medicine)

Abstract

Obesity and type 2 diabetes are the most frequent metabolic disorders, but their causes remain largely unclear. Insulin resistance, the common underlying abnormality, results from imbalance between energy intake and expenditure favouring nutrient-storage pathways, which evolved to maximize energy utilization and preserve adequate substrate supply to the brain. Initially, dysfunction of white adipose tissue and circulating metabolites modulate tissue communication and insulin signalling. However, when the energy imbalance is chronic, mechanisms such as inflammatory pathways accelerate these abnormalities. Here we summarize recent studies providing insights into insulin resistance and increased hepatic gluconeogenesis associated with obesity and type 2 diabetes, focusing on data from humans and relevant animal models.

Suggested Citation

  • Michael Roden & Gerald I. Shulman, 2019. "The integrative biology of type 2 diabetes," Nature, Nature, vol. 576(7785), pages 51-60, December.
    • Handle: RePEc:nat:nature:v:576:y:2019:i:7785:d:10.1038_s41586-019-1797-8
    DOI: 10.1038/s41586-019-1797-8
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    Cited by:

    1. Zvonimir Bosnić & František Babič & Viera Anderková & Mario Štefanić & Thomas Wittlinger & Ljiljana Trtica Majnarić, 2023. "A Critical Appraisal of the Diagnostic and Prognostic Utility of the Anti-Inflammatory Marker IL-37 in a Clinical Setting: A Case Study of Patients with Diabetes Type 2," IJERPH, MDPI, vol. 20(4), pages 1-19, February.
    2. Shaza B. Zaghlool & Anna Halama & Nisha Stephan & Valborg Gudmundsdottir & Vilmundur Gudnason & Lori L. Jennings & Manonanthini Thangam & Emma Ahlqvist & Rayaz A. Malik & Omar M. E. Albagha & Abdul Ba, 2022. "Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Emmanouela Tsagkaraki & Sarah M. Nicoloro & Tiffany DeSouza & Javier Solivan-Rivera & Anand Desai & Lawrence M. Lifshitz & Yuefei Shen & Mark Kelly & Adilson Guilherme & Felipe Henriques & Nadia Amran, 2021. "CRISPR-enhanced human adipocyte browning as cell therapy for metabolic disease," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    4. Dongliang Lu & Anyuan He & Min Tan & Marguerite Mrad & Amal El Daibani & Donghua Hu & Xuejing Liu & Brian Kleiboeker & Tao Che & Fong-Fu Hsu & Monika Bambouskova & Clay F. Semenkovich & Irfan J. Lodhi, 2024. "Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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