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Diabetologia. 2003 Feb;46(2):296-9. Epub 2003 Jan 31.

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

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  • 1Department of Medicine, The Medical School, University of Newcastle upon Tyne, Framlington Place, NE2 4HH Newcastle upon Tyne, United Kingdom.

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.

[PubMed - indexed for MEDLINE]
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