title: β-Cell dedifferentiation, reduced duct cell plasticity, and impaired β-cell mass regeneration in middle-aged rats.
abstract: Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration.
authors.affiliation: CIBER of Diabetes and Associated Metabolic Diseases, CIBERDEM, Barcelona, Spain; Bellvitge Biomedical Research Institute, IDIBELL, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain ntellez@ub.edu.
authors.forename: Noèlia
authors.identifier: 0000-0001-7879-3256
authors.initials: N
authors.lastname: Téllez
authors.affiliation: Bellvitge Biomedical Research Institute, IDIBELL, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Vilaseca
authors.affiliation: Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Martí
authors.affiliation: Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Pla
authors.affiliation: CIBER of Diabetes and Associated Metabolic Diseases, CIBERDEM, Barcelona, Spain; Bellvitge Biomedical Research Institute, IDIBELL, Barcelona, Spain; Endocrine Unit, Hospital Universitari de Bellvitge, Barcelona, Spain; and Department of Clinical Sciences, University of Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000502:physiology*; D000066670:Cell Plasticity; D048429:Cell Size; D005755:Gastrins / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010180:Pancreatectomy; D010183:Pancreatic Ducts / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005755:Gastrins; D009419:Nerve Tissue Proteins; D055758:SOX9 Transcription Factor; C498696:Neurog3 protein, rat
keywords: aging; duct cell plasticity; gastrin; regeneration; β-cell dedifferentiation; β-cell replication