Formation of a human β-cell population within pancreatic islets is set early in life

J Clin Endocrinol Metab. 2012 Sep;97(9):3197-206. doi: 10.1210/jc.2012-1206. Epub 2012 Jun 28.


Context: 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.

Design and 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.

Conclusion: Human baseline β-cell population and appropriate association with other islet cell types is established before 5 yr of age.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autopsy
  • Biomarkers
  • Cell Count
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Fluorescent Antibody Technique
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature
  • Insulin-Secreting Cells / physiology*
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / growth & development*
  • Middle Aged
  • Neurons / physiology
  • Pancreas, Exocrine / cytology
  • Pancreatic Hormones / analysis
  • Pancreatic Hormones / metabolism
  • Paraffin Embedding
  • Young Adult


  • Biomarkers
  • Pancreatic Hormones