title: Formation of a human β-cell population within pancreatic islets is set early in life.
abstract: BACKGROUND
  Insulin resistance can be compensated by increased functional pancreatic β-cell mass; otherwise, diabetes ensues. Such compensation depends not only on environmental and genetic factors but also on the baseline β-cell mass from which the expansion originates.
  
  
  OBJECTIVE
  Little is known about assembly of a baseline β-cell mass in humans. Here, we examined formation of β-cell populations relative to other pancreatic islet cell types and associated neurons throughout the normal human lifespan.
  
  
  METHODS
  Human pancreatic sections derived from normal cadavers aged 24 wk premature to 72 yr were examined by immunofluorescence. Insulin, glucagon, and somatostatin were used as markers for β-, α-, and δ-cells, respectively. Cytokeratin-19 marked ductal cells, Ki67 cell proliferation, and Tuj1 (neuronal class III β-tubulin) marked neurons.
  
  
  RESULTS
  Most β-cell neogenesis was observed preterm with a burst of β-cell proliferation peaking within the first 2 yr of life. Thereafter, little indication of β-cell growth was observed. Postnatal proliferation of α- and δ-cells was rarely seen, but a wave of ductal cell proliferation was found mostly associated with exocrine cell expansion. The β-cell to α-cell ratio doubled neonatally, reflecting increased growth of β-cells, but during childhood, there was a 7-fold change in the β-cell to δ-cell ratio, reflecting an additional loss of δ-cells. A close association of neurons to pancreatic islets was noted developmentally and retained throughout adulthood. Negligible neuronal association to exocrine pancreas was observed.
  
  
  CONCLUSIONS
  Human baseline β-cell population and appropriate association with other islet cell types is established before 5 yr of age.
authors: The Kovler Diabetes Center, University of Chicago, 900 East 57th Street, Chicago, Illinois 60637, USA.
authors: Brigid E
authors: BE
authors: Gregg
authors: Patrick C
authors: PC
authors: Moore
authors: Damien
authors: D
authors: Demozay
authors: Ben A
authors: BA
authors: Hall
authors: Mei
authors: M
authors: Li
authors: Aliya
authors: A
authors: Husain
authors: Amy J
authors: AJ
authors: Wright
authors: Mark A
authors: MA
authors: Atkinson
authors: Christopher J
authors: CJ
authors: Rhodes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001344:Autopsy; D015415:Biomarkers; D002452:Cell Count; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000254:growth & development*; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D046790:Pancreas, Exocrine / Q000166:cytology; D010187:Pancreatic Hormones / Q000032:analysis / Q000378:metabolism; D016612:Paraffin Embedding; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010187:Pancreatic Hormones