title: Decrease in Ins+Glut2LOβ-cells with advancing age in mouse and human pancreas.
abstract: The presence and location of resident pancreatic β-cell progenitors is controversial. A subpopulation of insulin-expressing but glucose transporter-2-low (Ins+Glut2LO) cells may represent multipotent pancreatic progenitors in adult mouse and in human islets, and they are enriched in small, extra-islet β-cell clusters (<5 β cells) in mice. Here, we sought to identify and compare the ontogeny of these cells in mouse and human pancreata throughout life. Mouse pancreata were collected at postnatal days 7, 14, 21, 28, and at 3, 6, 12, and 18 months of age, and in the first 28 days after β-cell mass depletion following streptozotocin (STZ) administration. Samples of human pancreas were examined during fetal life (22-30 weeks gestation), infancy (0-1 year), childhood (2-9), adolescence (10-17), and adulthood (18-80). Tissues were analyzed by immunohistochemistry for the expression and location of insulin, GLUT2 and Ki67. The proportion of β cells within clusters relative to that in islets was higher in pancreas of human than of mouse at all ages examined, and decreased significantly at adolescence. In mice, the total number of Ins+Glut2LOcells decreased after 7 days concurrent with the proportion of clusters. These cells were more abundant in clusters than in islets in both species. A positive association existed between the appearance of new β cells after the STZ treatment of young mice, particularly in clusters and smaller islets, and an increased proportional presence of Ins+Glut2LOcells during early β-cell regeneration. These data suggest that Ins+Glut2LOcells are preferentially located within β-cell clusters throughout life in pancreas of mouse and human, and may represent a source of β-cell plasticity.
authors.affiliation: Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada.|Department of Physiology & PharmacologyWestern University, London, Ontario, Canada.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Beamish
authors.affiliation: Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada.
authors.forename: Brenda J
authors.initials: BJ
authors.lastname: Strutt
authors.affiliation: Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada.|Department of Pathology and Laboratory MedicineWestern University, London, Ontario, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: Department of MedicineUniversity of Chicago, Chicago, Illinois, USA.
authors.forename: Manami
authors.initials: M
authors.lastname: Hara
authors.affiliation: Lawson Health Research InstituteSt Joseph Health Care, London, Ontario, Canada david.hill@lhrionhealth.ca.|Department of Physiology & PharmacologyWestern University, London, Ontario, Canada.|Department of MedicineWestern University, London, Ontario, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D012741:Sexual Maturation; D055815:Young Adult
chemical_list: D051273:Glucose Transporter Type 2; D007328:Insulin; C495680:SLC2A2 protein, human; C495682:Slc2a2 protein, mouse
keywords: Glut2; aging; islet; regeneration; β-cell