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

Authors :
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
Source :
Diabetologia [Diabetologia] 2010 Feb; Vol. 53 (2), pp. 321-30. Date of Electronic Publication: 2009 Oct 24.
Publication Year :
2010

Abstract

Aims/hypothesis: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusions/interpretation: 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.

Details

Language :
English
ISSN :
1432-0428
Volume :
53
Issue :
2
Database :
MEDLINE
Journal :
Diabetologia
Publication Type :
Academic Journal
Accession number :
19855953
Full Text :
https://doi.org/10.1007/s00125-009-1562-x