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Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats

Lookup NU author(s): Dr Helen Imrie


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Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders1−9. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension10, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells11−14. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosomes 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.

Publication metadata

Author(s): Aitman TJ, Gotoda T, Evans AL, Imrie H, Heath KE, Trembling PM, Truman H, Wallace CA, Rahman A, Dore C, Flint J, Kren V, Zidek V, Kurtz TW, Pravenec M, Scott J

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 1997

Volume: 16

Issue: 2

Pages: 197-201

Print publication date: 01/01/1997

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group


DOI: 10.1038/ng0697-197


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