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

doi:10.1016/j.cmet.2017.03.015

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

Pediatric and Adolescent Medicine

Research output: Contribution to journal › Article › peer-review

73 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 p16^ink4a, 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 language	English (US)
Pages (from-to)	898-910.e5
Journal	Cell Metabolism
Volume	25
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2017.03.015
State	Published - Apr 4 2017

Keywords

aging markers
beta-cell heterogeneity
islets

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2017.03.015

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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

Aguayo-Mazzucato, C, van Haaren, M, Mruk, M, Lee, TB, Crawford, C, Hollister-Lock, J, Sullivan, BA, Johnson, JW, Ebrahimi, A, Dreyfuss, JM, Van Deursen, J, Weir, GC & Bonner-Weir, S 2017, 'β Cell Aging Markers Have Heterogeneous Distribution and Are Induced by Insulin Resistance', Cell Metabolism, vol. 25, no. 4, pp. 898-910.e5. https://doi.org/10.1016/j.cmet.2017.03.015

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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.",

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AU - Hollister-Lock, Jennifer

AU - Sullivan, Brooke A.

AU - Johnson, James W.

AU - Ebrahimi, Aref

AU - Dreyfuss, Jonathan M.

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

Abstract

Keywords

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