Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets

被引：76

作者：

Cree, L. M. ^{[2
]}

Patel, S. K. ^{[3
]}

Pyle, A. ^{[2
]}

Lynn, S. ^{[4
]}

Turnbull, D. M. ^{[2
]}

Chinnery, P. F. ^{[2
]}

Walker, M. ^{[1
]}

机构：

[1] Newcastle Univ, Fac Med Sci, Sch Clin Med Sci, Diabet Res Grp,Med Sch, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Newcastle Univ, Fac Med Sci, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[3] Univ Melbourne, Dept Med, Cardiovasc Res Grp, Melbourne, Vic, Australia

[4] Newcastle Univ, Fac Med Sci, Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England

来源：

DIABETOLOGIA | 2008年 / 51卷 / 08期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

ageing; human islets; mitochondrial DNA copy number; mitochondrial DNA deletion; mitochondrial DNA depletion; pancreatic beta cell function;

D O I：

10.1007/s00125-008-1054-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aim/hipothesis Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. Methods We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets (n =20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. Results There was a significant negative correlation between mtDNA copy number and islet donor age (r=-0.53, p=0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged >= 50 years (n=8) compared with those aged <50 years (n=7) (median [interquartile range]: 418 [236-503] vs 596 [554-729] mtDNA copy number/diploid genome; p=0.032). None of the islet pmparations harboured high levels of deleted mtDNA affecting the major arc. Conclusion/interpretation Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity.

引用

页码：1440 / 1443

页数：4

共 12 条

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