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PMID: 19855953 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation.

Diabetologia ·Vol. 53 ·No. 2 ·2010-02-00 ·Pages 321-30

Cnop M, Hughes SJ, Igoillo-Esteve M, Hoppa MB, Sayyed F, van de Laar L, Gunter JH, de Koning EJ, Walls GV, Gray DW, Johnson PR, Hansen BC, Morris JF, Pipeleers-Marichal M, Cnop I, Clark A

Abstract

Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years. LB content was determined by electron microscopical morphometry in sections of beta cells from human (non-diabetic, n = 45; type 2 diabetic, n = 10) and non-human primates (n = 10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was estimated by three-dimensional (3D) mathematical modelling. LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n = 5) and alpha cells and in mouse beta cells (LB content in mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from >or=90% (<10 years) to >or=97% (>20 years) and remained constant thereafter. Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.

MeSH Terms
Adult Age Distribution Aging/physiology Animals Biomarkers/metabolism Cause of Death Cell Division Diabetes Mellitus, Type 2/pathology Humans Insulin-Secreting Cells/cytology,pathology,physiology Lipofuscin/metabolism Macaca mulatta Mice Mice, Inbred C57BL Models, Theoretical Pancreas/cytology,pathology Tissue Donors
Chemicals
Biomarkers Lipofuscin
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Cnop M
Laboratory of Experimental Medicine and Division of Endocrinology, Université Libre de Bruxelles, Brussels, Belgium.
Hughes S J
Igoillo-Esteve M
Hoppa M B
Sayyed F
van de Laar L
Gunter J H
de Koning E J P
Walls G V
Gray D W G
Johnson P R V
Hansen B C
Morris J F
Pipeleers-Marichal M
Cnop I
Clark A
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
1432-0428
DOI
10.1007/s00125-009-1562-x
Published
2010-02-00
Epub
2009-00-24
Pages
321-30
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
Grants
Wellcome Trust · United Kingdom
Multiple Sclerosis Society · 913 · United Kingdom
NIA NIH HHS · N01 AG-3-1012 · United States
Medical Research Council · G0501780 · United Kingdom
Department of Health · 913 · United Kingdom
External Links
PubMed source DOI: 10.1007/s00125-009-1562-x View journal details
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