ArticleNPJ Regenerative medicine2021
Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration.
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Article in NPJ Regenerative medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed.
- Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.Islets · 2026Article
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Acute and resolving inflammation differentially regulates beta cell function in mice via interactions between peritoneal and islet-associated macrophages.Diabetologia · 2026Article
- Transient ER stress cell-autonomously promotes beta cell cycling in mice.Diabetologia · 2026Article
- Fixation matters: duration in fixative prior to immunofluorescent analysis directly impacts macrophage visualization in epithelial tissues.Discovery immunology · 2026Article
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Bioengineering Platelets Presenting PD-L1, Galectin-9 and BTLA to Ameliorate Type 1 Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Single-cell RNA sequencing identifies endothelial-derived HBEGF as promoting pancreatic beta cell proliferation in mice via the EGFR-Kmt5a-H4K20me pathway.Diabetologia · 2025Article
- Stressed β-cells contribute to loss of peri-islet extracellular matrix in type 1 diabetes.Frontiers in endocrinology · 2025Article
- Mosaic ablation of pancreatic β cells induces de-differentiation and repetitive proliferation of residual β cells in adult mice.iScience · 2024Article
- The Pivotal Role of Macrophages in the Pathogenesis of Pancreatic Diseases.International journal of molecular sciences · 2024Review
- Vascular Contribution to Lung Repair and Fibrosis.American journal of respiratory cell and molecular biology · 2023Review
- Article
- Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss.American journal of physiology. Endocrinology and metabolism · 2023Article
- Pericytes modulate islet immune cells and insulin secretion through Interleukin-33 production in mice.Frontiers in endocrinology · 2023Article
- Using single-cell multi-omics screening of human fetal pancreas to identify novel players in human beta cell development.Diabetic medicine : a journal of the British Diabetic Association · 2022Review
- Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells.Transplant international : official journal of the European Society for Organ Transplantation · 2022Review
- Interactions between islets and regulatory immune cells in health and type 1 diabetes.Diabetologia · 2021Review
- Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.Frontiers in endocrinology · 2021Review
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Authors and funding
12 authors.
Diane C Saunders *Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-8849-6746
Kristie I Aamodt *Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-0065-0786
Tiffany M RichardsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-0272-6804
Alexander J HopkirkDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
Radhika AramandlaDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
Greg PoffenbergerDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
Regina JenkinsDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
David K FlahertyFlow Cytometry Shared Resource, Vanderbilt University Medical Center, Nashville, TN, USA.
Nripesh PrasadHudson Alpha Institute of Biotechnology, Huntsville, AL, USA.
Shawn E LevyHudson Alpha Institute of Biotechnology, Huntsville, AL, USA.
Alvin C PowersDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA. al.powers@vumc.org.
Marcela BrissovaDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA. marcela.brissova@vumc.org.ORCID http://orcid.org/0000-0002-4999-3280
Funding
Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8MCoordinating Center for Beta Cell Biology ConsortiumU01DK072473 · NIDDK · VANDERBILT UNIVERSITY · PI MAGNUSON, MARK A · 2005 to 2014
$61.0MTranslational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9MVanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3MTRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI POWERS, ALVIN C · 1986 to 2011
$28.1MShop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6MVanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9MMolecular Mechanisms of Human and Murine Beta Cell Proliferation and RegenerationU01DK089572 · NIDDK · VANDERBILT UNIVERSITY · PI GREINER, DALE LESLIE, HARLAN, DAVID MARSHALL · 2010 to 2014
$8.4MDiscovery of Pancreatic Signatures in Type 2 Diabetes MellitusR24DK106755 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CAI, LONG, CAPRIOLI, RICHARD M · 2015 to 2019
$6.2MMolecular Mechanisms of Physiologic Beta Cell Growth in Juvenile Human PancreasUC4DK104211 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KIM, SEUNG K, POWERS, ALVIN C · 2014 to 2015
$4.0MMolecular Mechanisms of Postnatal Islet alpha-cell ProliferationR01DK117147 · NIDDK · VANDERBILT UNIVERSITY · PI CHEN, WENBIAO, POWERS, ALVIN C · 2019 to 2023
$3.1MIslet Biology in Cystic Fibrosis Related DiabetesR01DK097829 · NIDDK · PACIFIC NORTHWEST RESEARCH INSTITUTE · PI AGUILAR-BRYAN, LYDIA, POWERS, ALVIN C · 2012 to 2016
$2.9MNCI NIH HHS P30 CA068485NEI NIH HHS P30 EY008126NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK068764NIDDK NIH HHS R01 DK069603NIDDK NIH HHS R01 DK094199NIDDK NIH HHS R01 DK097829NIDDK NIH HHS R01 DK117147NIDDK NIH HHS R21 DK062641NIDDK NIH HHS R21 DK063439NIDDK NIH HHS R21 DK066636NIDDK NIH HHS R24 DK106755NIDDK NIH HHS R33 DK066636NIDDK NIH HHS U01 DK072473NIDDK NIH HHS U01 DK089572NIDDK NIH HHS U24 DK059637NIDDK NIH HHS UC4 DK104211U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P30 CA68485U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK058404U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK104211U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK106755U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK117147U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK20593U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK62641U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK63439U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK66636U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK68764U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK69603U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK89572U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK94199U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK97829
Abstract
Endogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.
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