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Human islets contain four distinct subtypes of β cells

Author

Listed:
  • Craig Dorrell

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

  • Jonathan Schug

    (Obesity, and Metabolism; University of Pennsylvania School of Medicine
    University of Pennsylvania School of Medicine)

  • Pamela S. Canaday

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

  • Holger A. Russ

    (Diabetes Center, University of California San Francisco)

  • Branden D. Tarlow

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

  • Maria T. Grompe

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

  • Tamara Horton

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road
    Present address: Genentech Inc., San Francisco, California 94080, USA.)

  • Matthias Hebrok

    (Diabetes Center, University of California San Francisco)

  • Philip R. Streeter

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

  • Klaus H. Kaestner

    (Obesity, and Metabolism; University of Pennsylvania School of Medicine
    University of Pennsylvania School of Medicine)

  • Markus Grompe

    (Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road)

Abstract

Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1–4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant.

Suggested Citation

  • Craig Dorrell & Jonathan Schug & Pamela S. Canaday & Holger A. Russ & Branden D. Tarlow & Maria T. Grompe & Tamara Horton & Matthias Hebrok & Philip R. Streeter & Klaus H. Kaestner & Markus Grompe, 2016. "Human islets contain four distinct subtypes of β cells," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11756
    DOI: 10.1038/ncomms11756
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    Cited by:

    1. Monica E. Brown & Verda E. Miranda & Simone Nevills & Ruiying Hu & Prasanna K. Dadi & Alan J. Simmons & Yanwen Xu & Yilin Yang & Mahircan Yagan & Sadia Najam & Leesa L. Sampson & Mark A. Magnuson & Da, 2025. "Pancreatic islet β-cell subtypes are derived from biochemically-distinct and nutritionally-regulated islet progenitors," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    2. Léon Gurp & Leon Fodoulian & Daniel Oropeza & Kenichiro Furuyama & Eva Bru-Tari & Anh Nguyet Vu & John S. Kaddis & Iván Rodríguez & Fabrizio Thorel & Pedro L. Herrera, 2022. "Generation of human islet cell type-specific identity genesets," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Keiichi Katsumoto & Siham Yennek & Chunguang Chen & Luis Fernando Delgadillo Silva & Sofia Traikov & Dror Sever & Ajuna Azad & Jingdong Shan & Seppo Vainio & Nikolay Ninov & Stephan Speier & Anne Grap, 2022. "Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Chen Weng & Anniya Gu & Shanshan Zhang & Leina Lu & Luxin Ke & Peidong Gao & Xiaoxiao Liu & Yuntong Wang & Peinan Hu & Dylan Plummer & Elise MacDonald & Saixian Zhang & Jiajia Xi & Sisi Lai & Konstant, 2023. "Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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