The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome
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- Kitt Falk Petersen
- Departments of *Internal Medicine;
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- Sylvie Dufour
- Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536; and
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- David B. Savage
- Departments of *Internal Medicine;
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- Stefan Bilz
- Departments of *Internal Medicine;
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- Gina Solomon
- Departments of *Internal Medicine;
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- Shin Yonemitsu
- Departments of *Internal Medicine;
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- Gary W. Cline
- Departments of *Internal Medicine;
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- Douglas Befroy
- Departments of *Internal Medicine;
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- Laura Zemany
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
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- Barbara B. Kahn
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
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- Xenophon Papademetris
- Diagnostic Radiology and Biomedical Engineering;
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- Douglas L. Rothman
- Diagnostic Radiology and Biomedical Engineering;
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- Gerald I. Shulman
- Departments of *Internal Medicine;
説明
<jats:p> We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by ≈60% in young, lean, insulin-resistant subjects compared with a similar cohort of age–weight–body mass index–activity-matched, insulin-sensitive, control subjects. In contrast, hepatic <jats:italic>de novo</jats:italic> lipogenesis and hepatic triglyceride synthesis were both increased by >2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an ≈20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-α, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic <jats:italic>de novo</jats:italic> lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-α, IL-6, high-molecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 104 (31), 12587-12594, 2007-07-31
Proceedings of the National Academy of Sciences