A Role for Sphingolipids in Producing the Common Features of Type 2 Diabetes, Metabolic Syndrome X, and Cushing’s Syndrome
- Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, Utah
- Address correspondence and reprint requests to Scott A. Summers, Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132. E-mail: scott.summers{at}hsc.utah.edu
Abstract
Metabolic syndrome X and type 2 diabetes share many metabolic and morphological similarities with Cushing’s syndrome, a rare disorder caused by systemic glucocorticoid excess. Pathologies frequently associated with these diseases include insulin resistance, atherosclerosis, susceptibility to infection, poor wound healing, and hypertension. The similarity of the clinical profiles associated with these disorders suggests the influence of a common molecular mechanism for disease onset. Interestingly, numerous studies identify ceramides and other sphingolipids as potential contributors to these sequelae. Herein we review studies demonstrating that aberrant ceramide accumulation contributes to the development of the deleterious clinical manifestations associated with these diseases.
- FFA, free fatty acid
- IRS, insulin receptor substrate
- PI3K, phosphatidylinositol 3-kinase
- PKB, protein kinase B
- PPAR, peroxisome proliferator–activated receptor
- S1P, sphingosine 1-phosphate
- SPT, serine palmitoyltransferase
- TNF, tumor necrosis factor
- TZD, thiazolidinedione
Footnotes
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- Accepted December 6, 2004.
- Received October 1, 2004.
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