AJP - Endo Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 296: E672-E680, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90839.2008
0193-1849/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
296/4/E672    most recent
90839.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bensch, K. G.
Right arrow Articles by Corbett, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bensch, K. G.
Right arrow Articles by Corbett, J. A.

Selective mtDNA mutation accumulation results in β-cell apoptosis and diabetes development

Kenneth G. Bensch,1 Justin L. Mott,2 Shin-Wen Chang,2 Polly A. Hansen,3 Michael A. Moxley,1 Kari T. Chambers,1 Wieke de Graaf,3 H. Peter Zassenhaus,2 and John A. Corbett3

1Edward A. Doisy Department of Biochemistry and Molecular Biology and 2Department of Molecular Microbiology and Immunology, St. Louis University School of Medicine, St. Louis, Missouri; and 3Comprehensive Diabetes Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 14 October 2008 ; accepted in final form 13 January 2009

To test the hypothesis that somatic mitochondrial (mt)DNA mutation accumulation predisposes mice to β-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 β-cell mass. Importantly, apoptosis of β-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 β-cell mass and diabetes development.

mitochondrial deoxyribonucleic acid; insulin; islet


Address for reprint requests and other correspondence: H. P. Zassenhaus, Dept. of Molecular Microbiology and Immunology, St. Louis Univ. School of Medicine, St. Louis, MO 63104 (e-mail: zassenp{at}SLU.edu); or J. A. Corbett, The Comprehensive Diabetes Center, Univ. of Alabama Birmingham, 12 Floor Shelby, 1530 3rd Ave. South, Birmingham, AL 35294 (email: corbettj{at}UAB.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.