β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance

Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B. Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A. Sullivan, James W. Johnson, Aref Ebrahimi, Jonathan M. Dreyfuss, Jan Van Deursen, Gordon C. Weir, Susan Bonner-Weir

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16ink4a, p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas. Acute induction of insulin resistance with an insulin receptor antagonist or chronic ER stress resulted in increased expression of aging markers, providing insight into how metabolic stress might accelerate dysfunction and decline of β cells. These novel findings about β cell and islet heterogeneity, and how they change with age, open up an entirely new set of questions about the pathogenesis of type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)898-910.e5
JournalCell Metabolism
Volume25
Issue number4
DOIs
StatePublished - Apr 4 2017

Keywords

  • aging markers
  • beta-cell heterogeneity
  • islets

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Aguayo-Mazzucato, C., van Haaren, M., Mruk, M., Lee, T. B., Crawford, C., Hollister-Lock, J., Sullivan, B. A., Johnson, J. W., Ebrahimi, A., Dreyfuss, J. M., Van Deursen, J., Weir, G. C., & Bonner-Weir, S. (2017). β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance. Cell Metabolism, 25(4), 898-910.e5. https://doi.org/10.1016/j.cmet.2017.03.015