Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance

Kitt Falk Petersen, Douglas Befroy, Sylvie Dufour, James Dziura, Charlotte Ariyan, Douglas L. Rothman, Loretta DiPietro, Gary W. Cline, Gerald I. Shulman

doi:10.1126/science.1082889

Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance

DOI Web Site 被引用文献75件

Kitt Falk Petersen

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Douglas Befroy

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Sylvie Dufour

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
James Dziura

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Charlotte Ariyan

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Douglas L. Rothman

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Loretta DiPietro

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Gary W. Cline

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Gerald I. Shulman

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.

抄録

<jats:p> Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by <jats:sup>1</jats:sup> Hnuclear magnetic resonance (NMR) spectroscopy, and with a ∼40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo <jats:sup>13</jats:sup> C/ <jats:sup>31</jats:sup> P NMR spectroscopy. These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. </jats:p>