title: Young capillary vessels rejuvenate aged pancreatic islets.
abstract: Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; Center for Plant Aging Research, Institute for Basic Science, and Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;
authors.forename: Joana
authors.initials: J
authors.lastname: Almaça
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;
authors.forename: Judith
authors.initials: J
authors.lastname: Molina
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136; Lee Kong Chien School of Medicine, Nanyang Technical University, Singapore; Imperial College, London, United Kingdom;
authors.forename: Rafael
authors.initials: R
authors.lastname: Arrojo E Drigo
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136;
authors.forename: Midhat H
authors.initials: MH
authors.lastname: Abdulreda
authors.affiliation: Division of NanoBio Technology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea;
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Jeon
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; Lee Kong Chien School of Medicine, Nanyang Technical University, Singapore; Imperial College, London, United Kingdom; Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm SE-17177, Sweden; and acaicedo@med.miami.edu per-olof.berggren@ki.se nam@dgist.ac.kr.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136; Department of Physiology and Biophysics and Program in Neuroscience, University of Miami Miller School of Medicine, Miami, FL 33136 acaicedo@med.miami.edu per-olof.berggren@ki.se nam@dgist.ac.kr.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Caicedo
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, and Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea; acaicedo@med.miami.edu per-olof.berggren@ki.se nam@dgist.ac.kr.
authors.forename: Hong Gil
authors.initials: HG
authors.lastname: Nam
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002196:Capillaries / Q000502:physiology*; D049109:Cell Proliferation; D005355:Fibrosis; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010477:Perfusion; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
keywords: aging; glucose metabolism; insulin secretion; pancreatic islets; vasculature