Submit a Letter to the Editor for:
Charlotte Ling, Pernille Poulsen, Emma Carlsson, Martin Ridderstråle, Peter Almgren, Jørgen Wojtaszewski, Henning Beck-Nielsen, Leif Groop, Allan Vaag
J Clin Invest. 2004;
114(10):1518
doi:10.1172/JCI21889
Abstract |
Full text
|
PDF
G
enetic and environmental factors contribute to age-dependent susceptibility to type 2 diabetes. Recent studies have reported reduced expression of PPARγ coactivator 1α (PGC-1α) and PGC-1β genes in skeletal muscle from type 2 diabetic patients, but it is not known whether this is an inherited or acquired defect. To address this question we studied expression of these genes in muscle biopsies obtained from young and elderly dizygotic and monozygotic twins without known diabetes before and after insulin stimulation and related the expression to a Gly482Ser variant in the PGC-1α gene. Insulin increased and aging reduced skeletal muscle PGC-1α and PGC-1β mRNA levels. This age-dependent decrease in muscle gene expression was partially heritable and influenced by the PGC-1α Gly482Ser polymorphism. In addition, sex, birth weight, and aerobic capacity influenced expression of PGC-1α in a complex fashion. Whereas expression of PGC-1α in muscle was positively related to insulin-stimulated glucose uptake and oxidation, PGC-1β expression was positively related to fat oxidation and nonoxidative glucose metabolism. We conclude that skeletal muscle PGC-1α and PGC-1β expression are stimulated by insulin and reduced by aging. The data also suggest different regulatory functions for PGC-1α and PGC-1β on glucose and fat oxidation in muscle cells. The finding that the age-dependent decrease in the expression of these key genes regulating oxidative phosphorylation is under genetic control could provide an explanation by which an environmental trigger (age) modifies genetic susceptibility to type 2 diabetes.
Guidelines:
The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. All accepted letters will be posted on our website within one week of acceptance. The Editors reserve the right to edit any letter for length, content, and clarity. Authors of all accepted letters will be asked to preview any changes. Authors will be notified by e-mail if their letters were not accepted. As this is a final decision, no appeals will be considered.
Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML, if you wish. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editor directly at editors@the-jci.org.
