Elastin Insufficiency Predisposes Mice to Impaired Glucose Metabolism
| Autor: | Beth A. Kozel, Justine A. Maedeker, Tezin A. Walji, Clarissa S. Craft, Jessica E. Wagenseil, Robert P. Mecham, Kellie V. Stoka, Antea J. DeMarsilis |
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| Rok vydání: | 2014 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Williams syndrome Adipose tissue 030209 endocrinology & metabolism Inflammation Carbohydrate metabolism Article Impaired glucose tolerance 03 medical and health sciences 0302 clinical medicine Diabetes mellitus Internal medicine medicine 030304 developmental biology 0303 health sciences biology business.industry Diabetes Cardiovascular disease medicine.disease Elastic fiber Elastin medicine.anatomical_structure Endocrinology biology.protein medicine.symptom business |
| Zdroj: | Journal of molecular and genetic medicine : an international journal of biomedical research |
| ISSN: | 1747-0862 |
| DOI: | 10.4172/1747-0862.1000129 |
| Popis: | Williams-Beuren syndrome is the consequence of a large contiguous-gene deletion on the seventh human chromosome that includes the elastin gene. Elastin is an extracellular matrix protein responsible for the cardiovascular abnormalities associated with Williams’s syndrome, including hypertension and aortic stenosis. A high percentage of individuals with Williams’s syndrome also have impaired glucose tolerance, independent of traditional risk factors for diabetes. Here, we show that murine adipose tissue does assemble elastic fibers; however, isolated elastin insufficiency (Eln+/−) in mice does not independently influence glucose metabolism or tissue lipid accumulation. Similarly, isolated ApoE deficiency (ApoE−/−), a model of hyperlipidemia and atherosclerosis, does not impair insulin sensitivity. However, Eln+/−; ApoE−/− double mutant mice exhibit notable hyperglycemia, adipocyte hypertrophy, inflammation of adipose tissue, and ectopic lipid accumulation in liver tissue. Further, Eln+/−; ApoE−/− mutants have significant impairment of insulin sensitivity by insulin tolerance testing, independent of body weight or diet, suggesting that elastin insufficiency predisposes to metabolic disease in susceptible individuals. |
| Databáze: | OpenAIRE |
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