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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cooksey, Robert C. Rutter, Jared Abel, E. Dale Smith, Tammy L. Cardon, Caleb M. Swiatek, Wojtek Hao, Huai-xiang Boudina, Sihem Mcclain, Donald A. Wilde, James |
| Description | Author Affiliation: Hao HX ( Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.); |
| Abstract | The metabolic syndrome, a complex set of phenotypes typically associated with obesity and diabetes, is an increasing threat to global public health. Fundamentally, the metabolic syndrome is caused by a failure to properly sense and respond to cellular metabolic cues. We studied the role of the cellular metabolic sensor PAS kinase (PASK) in the pathogenesis of metabolic disease by using PASK(-/-) mice. We identified tissue-specific metabolic phenotypes caused by PASK deletion consistent with its role as a metabolic sensor. Specifically, PASK(-/-) mice exhibited impaired glucose-stimulated insulin secretion in pancreatic beta-cells, altered triglyceride storage in liver, and increased metabolic rate in skeletal muscle. Further, PASK deletion caused nearly complete protection from the deleterious effects of a high-fat diet including obesity and insulin resistance. We also demonstrate that these cellular effects, increased rate of oxidative metabolism and ATP production, occur in cultured cells. We therefore hypothesize that PASK acts in a cell-autonomous manner to maintain cellular energy homeostasis and is a potential therapeutic target for metabolic disease. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 39 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Glucose Metabolism Protein-Serine-Threonine Kinases Genetics Physiology Animals Cell Line Gene Deletion Insulin Secretion Islets Of Langerhans Liver Mice Mice, Inbred C57BL Mice, Transgenic Muscle, Skeletal Oxygen Triglycerides Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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