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

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اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Publisher Information:
      2010
    • نبذة مختصرة :
      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 >or=90% (<10 years) to >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.
      Journal Article
      Research Support, N.I.H. Extramural
      Research Support, Non-U.S. Gov't
      SCOPUS: ar.j
      info:eu-repo/semantics/published
    • الموضوع:
      Sciences bio-médicales et agricoles; Adult; Age Distribution; Aging -- physiology; Animals; Biological Markers -- metabolism; Cause of Death; Cell Division; Diabetes Mellitus, Type 2 -- pathology; Humans; Insulin-Secreting Cells -- cytology; Insulin-Secreting Cells -- pathology; Insulin-Secreting Cells -- physiology; Lipofuscin -- metabolism; Macaca mulatta; Mice; Mice, Inbred C57BL; Models, Theoretical; Pancreas -- cytology; Pancreas -- pathology; Tissue Donors; info:eu-repo/semantics/article; info:ulb-repo/semantics/articlePeerReview; info:ulb-repo/semantics/openurl/article
    • Availability:
      Open access content. Open access content
      1 full-text file(s): info:eu-repo/semantics/restrictedAccess
    • Note:
      1 full-text file(s): application/pdf
      English
    • Other Numbers:
      EQY oai:dipot.ulb.ac.be:2013/59796
      uri/info:doi/10.1007/s00125-009-1562-x
      uri/info:pmid/19855953
      uri/info:scp/77949289481
      1363718908
    • Contributing Source:
      UNIVERSITE LIBRE DE BRUXELLES
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1363718908
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