The Impact of Aging on Macrophages in the Pancreatic Islet

Faculty Mentor Information

Dr. Lizbeth de la Cruz, Idaho State University

Presentation Date

7-15-2026

Abstract

Islet-resident macrophages are immune cells within pancreatic islets that play key roles in maintaining endocrine homeostasis and surveilling the local microenvironment. However, how aging affects these macrophages and their function in islets remains poorly understood. This study will examine how aging influences the abundance and spatial organization of islet-resident macrophages, with emphasis on their relationship to islet vasculature. We hypothesize that macrophage number increases with age and is associated with age-related enlargement of islet blood vessels, ultimately contributing to impaired islet function. Pancreatic tissues will be collected from young, middle-aged, and old mice, then sectioned and immunolabeled with antibodies against insulin, CD31 (blood vessels markers) and CD11 and F4/80 (macrophage markers). Confocal microscopy will be used for imaging. Preliminary work confirmed CD11 and F4/80 as reliable macrophage markers in islets. Future analyses will quantify macrophage abundance across age groups and assess their spatial relationship with islet vasculature to determine whether macrophages accumulate with age and whether this correlates with vascular remodeling and impaired islet structure and function. This work aims to provide insight into pancreatic aging and establish a foundation for understanding immune–vascular interactions in the pathogenesis of type 2 diabetes. Supported by NIH/NIGMS IDeA Program Grant #P20GM103408.

Works Cited

  • Arda, H. Efsun et al. (2016). Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function. Cell Metabolism, 23(5), 909–920. https://doi.org/10.1016/j.cmet.2016.04.002
  • Barajas-Martínez, A., Easton, J. F., Rivera, A. L., Martínez-Tapia, R., Robles-Cabrera, A., & Stephens, C. R. (2020). Metabolic Physiological Networks: The Impact of Age. Frontiers in Physiology, 11, 587994. https://doi.org/10.3389/fphys.2020.587994
  • Félix-Martínez GJ, de la Cruz L, Whisman D and Godínez-Fernández JR (2025) Impact of vascular density on pancreatic islet viability: a computational study. Front. Physiol. 16:1707026. https://doi/10.3389/fphys.2025.1707026
  • J.A. Carrero, D.P. McCarthy, S.T. Ferris, X. Wan, H. Hu, B.H. Zinselmeyer, A.N. Vomund, & E.R. Unanue, (2017) Resident Macrophages of Pancreatic Islets Have a Seminal Role in the Initiation of Autoimmune Diabetes of NOD Mice, Proc. Natl. Acad. Sci. U.S.A. 114 (48) E10418-E10427, https://doi.org/10.1073/pnas.1713543114
  • Leete, P. (2023). Type 1 diabetes in the pancreas: A histological perspective. Diabetic Medicine, 40(12), 1–19. https://doi.org/10.1111/dme.15228
  • Rong, B., Jiang, H., Zhu, W., Yang, G., Zhou, X., Lyu, Z., Li, X., & Zhang, J. (2025). Unraveling the role of macrophages in diabetes: Impaired phagocytic function and therapeutic prospects. Medicine, 104(8), e41613. https://doi.org/10.1097/MD.0000000000041613
  • ADA. (n.d.). American Diabetes Association. Understanding Type 2 Diabetes https://diabetes.org/about-diabetes/type-2
  • Elliott, A. D. (2020, March). Confocal Microscopy: Principles and Modern Practices – PMC. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6961134/

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    The Impact of Aging on Macrophages in the Pancreatic Islet

    Islet-resident macrophages are immune cells within pancreatic islets that play key roles in maintaining endocrine homeostasis and surveilling the local microenvironment. However, how aging affects these macrophages and their function in islets remains poorly understood. This study will examine how aging influences the abundance and spatial organization of islet-resident macrophages, with emphasis on their relationship to islet vasculature. We hypothesize that macrophage number increases with age and is associated with age-related enlargement of islet blood vessels, ultimately contributing to impaired islet function. Pancreatic tissues will be collected from young, middle-aged, and old mice, then sectioned and immunolabeled with antibodies against insulin, CD31 (blood vessels markers) and CD11 and F4/80 (macrophage markers). Confocal microscopy will be used for imaging. Preliminary work confirmed CD11 and F4/80 as reliable macrophage markers in islets. Future analyses will quantify macrophage abundance across age groups and assess their spatial relationship with islet vasculature to determine whether macrophages accumulate with age and whether this correlates with vascular remodeling and impaired islet structure and function. This work aims to provide insight into pancreatic aging and establish a foundation for understanding immune–vascular interactions in the pathogenesis of type 2 diabetes. Supported by NIH/NIGMS IDeA Program Grant #P20GM103408.

    Works Cited

  • Arda, H. Efsun et al. (2016). Age-Dependent Pancreatic Gene Regulation Reveals Mechanisms Governing Human β Cell Function. Cell Metabolism, 23(5), 909–920. https://doi.org/10.1016/j.cmet.2016.04.002
  • Barajas-Martínez, A., Easton, J. F., Rivera, A. L., Martínez-Tapia, R., Robles-Cabrera, A., & Stephens, C. R. (2020). Metabolic Physiological Networks: The Impact of Age. Frontiers in Physiology, 11, 587994. https://doi.org/10.3389/fphys.2020.587994
  • Félix-Martínez GJ, de la Cruz L, Whisman D and Godínez-Fernández JR (2025) Impact of vascular density on pancreatic islet viability: a computational study. Front. Physiol. 16:1707026. https://doi/10.3389/fphys.2025.1707026
  • J.A. Carrero, D.P. McCarthy, S.T. Ferris, X. Wan, H. Hu, B.H. Zinselmeyer, A.N. Vomund, & E.R. Unanue, (2017) Resident Macrophages of Pancreatic Islets Have a Seminal Role in the Initiation of Autoimmune Diabetes of NOD Mice, Proc. Natl. Acad. Sci. U.S.A. 114 (48) E10418-E10427, https://doi.org/10.1073/pnas.1713543114
  • Leete, P. (2023). Type 1 diabetes in the pancreas: A histological perspective. Diabetic Medicine, 40(12), 1–19. https://doi.org/10.1111/dme.15228
  • Rong, B., Jiang, H., Zhu, W., Yang, G., Zhou, X., Lyu, Z., Li, X., & Zhang, J. (2025). Unraveling the role of macrophages in diabetes: Impaired phagocytic function and therapeutic prospects. Medicine, 104(8), e41613. https://doi.org/10.1097/MD.0000000000041613
  • ADA. (n.d.). American Diabetes Association. Understanding Type 2 Diabetes https://diabetes.org/about-diabetes/type-2
  • Elliott, A. D. (2020, March). Confocal Microscopy: Principles and Modern Practices – PMC. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6961134/

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