| First Author | Bensch KG | Year | 2009 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 296 |
| Issue | 4 | Pages | E672-80 |
| PubMed ID | 19158322 | Mgi Jnum | J:148133 |
| Mgi Id | MGI:3843575 | Doi | 10.1152/ajpendo.90839.2008 |
| Citation | Bensch KG, et al. (2009) Selective mtDNA mutation accumulation results in beta-cell apoptosis and diabetes development. Am J Physiol Endocrinol Metab 296(4):E672-80 |
| abstractText | To test the hypothesis that somatic mitochondrial (mt)DNA mutation accumulation predisposes mice to beta-cell loss and diabetes development, transgenic mice expressing a proofreading-deficient mtDNA polymerase-gamma under the control of the rat insulin-1 promoter were generated. At 6 wk of age, mtDNA mutations reached 0.01% (1.05 mutations/10,000 bp) in islets isolated from transgenic mice. This mutational burden is associated with impaired glucose tolerance and a diabetes prevalence of 52% in male transgenic mice. Female transgenic mice maintain slightly elevated fasting glucose levels, mild glucose intolerance, and a diabetes prevalence of 14%. Diabetes in transgenic animals is associated with insulin insufficiency that results from a significant reduction in beta-cell mass. Importantly, apoptosis of beta-cells is increased 7-fold in female and 11-fold in male transgenic mice compared with littermate controls. These results are consistent with a causative role of somatic mtDNA mutation accumulation in the loss of beta-cell mass and diabetes development. |
