Format

Send to

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

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

Author information

1
The Kovler Diabetes Center, University of Chicago, 900 East 57th Street, Chicago, Illinois 60637, USA.

Abstract

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.

PMID:
22745242
PMCID:
PMC3431572
DOI:
10.1210/jc.2012-1206
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center