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

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    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

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