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Heteroplasmic ratio of the A3243G mitochondrial DNA mutation in single pancreatic beta cells

Lookup NU author(s): Dr Stephen Lynn, Dr Gillian Borthwick, Richard Charnley, Professor Mark Walker, Professor Doug Turnbull

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Abstract

Aims/Hypothesis. To examine whether there is a high content of mutated mitochondrial DNA in individual pancreatic beta cells from a patient with the A3243G mitochondrial DNA mutation. Methods. Tissues were available from a patient with diabetes and the A3243G mutation including pancreatic tissue. We quantified the amount of mutated mitochondrial DNA in tissue homogenates and single pancreatic beta cells using hot last cycle PCR. Results. The percentage ratio of mutated to wild-type mtDNA was high in tissues such as muscle and brain (>60%), but surprisingly low in both pancreatic islets and in individual beta cells from these islets. The islets were smaller in the patient than in control subjects in keeping with a decreased beta-cell mass. Conclusions/interpretation. These observations suggest that either the beta cells show increased sensitivity to the effects mtDNA mutations on respiratory chain function, and/or cells with a high mutant load are preferentially removed leading to a progressive decrease in the islet beta-cell mass.


Publication metadata

Author(s): Lynn S, Borthwick GM, Charnley RM, Walker M, Turnbull DM

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2003

Volume: 46

Issue: 2

Pages: 296-299

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer

PubMed id: 12627331


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