The long lifespan and low 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, A Clark

    Research output: Contribution to journalArticle

    158 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 <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. 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 <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from ≥90% (<10 years) to ≥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
    Issue number2
    Publication statusPublished - Feb 2010

    Keywords

    • Ageing
    • Human
    • Islet
    • Longevity
    • Mathematical modelling

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