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

M Cnop, S.j. Hughes, M Igoillo-Esteve, M.b. Hoppa, F Sayyed, L Van De Laar, J.h. Gunter, E.j.p. De Koning, G.v. Walls, D.w.g. Gray, P.r.v. Johnson, B.c. Hansen, J.f. Morris, Miriam Marichal, Ivan Cnop

Research output: Contribution to journalArticlepeer-review

174 Citations (Scopus)

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 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. 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. 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 the LB-positive human beta cells (representing aged cells) increased from >or=90%
(or=97% (>20 years) and remained constant thereafter.
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.
Original languageEnglish
Pages (from-to)321-330
Number of pages10
JournalDiabetologia
Volume53
Publication statusPublished - 2010

Keywords

  • Lipofuscin
  • Age distribution
  • Cse of Death

Fingerprint

Dive into the research topics of 'The long lifespan and how turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation.'. Together they form a unique fingerprint.

Cite this