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

被引:182
作者
Cnop, M. [2 ,3 ]
Hughes, S. J. [4 ]
Igoillo-Esteve, M. [2 ,3 ]
Hoppa, M. B. [1 ]
Sayyed, F. [1 ]
van de Laar, L. [1 ]
Gunter, J. H. [1 ]
de Koning, E. J. P. [1 ]
Walls, G. V. [5 ]
Gray, D. W. G. [4 ]
Johnson, P. R. V. [4 ]
Hansen, B. C. [6 ]
Morris, J. F. [7 ]
Pipeleers-Marichal, M. [8 ]
Cnop, I. [9 ]
Clark, A. [1 ]
机构
[1] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Diabet Res Labs, Oxford OX3 7LJ, England
[2] Univ Libre Bruxelles, Expt Med Lab, Brussels, Belgium
[3] Univ Libre Bruxelles, Div Endocrinol, Brussels, Belgium
[4] Churchill Hosp, Nuffield Dept Surg, DRWF Islet Isolat Facil, Oxford OX3 7LJ, England
[5] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Acad Endocrine Unit, Oxford OX3 7LJ, England
[6] Univ S Florida, Coll Med, Obes Diabet & Aging Res Ctr, Tampa, FL USA
[7] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England
[8] Vrije Univ Brussel, Diabet Res Ctr, Brussels, Belgium
[9] Vrije Univ Brussel, Dept Math, Brussels, Belgium
基金
英国惠康基金;
关键词
Ageing; Human; Islet; Longevity; Mathematical modelling; Monkey; Mouse; Neogenesis; Pancreatic beta cell; Type; 2; diabetes; LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS; PARTIAL-PANCREATECTOMY; INSULIN-SECRETION; MASS; AGE; PROLIFERATION; REGENERATION; APOPTOSIS; BIRTH;
D O I
10.1007/s00125-009-1562-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. 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. 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 a parts per thousand yen90% (< 10 years) to a parts per thousand yen97% (> 20 years) and remained constant thereafter. 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.
引用
收藏
页码:321 / 330
页数:10
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