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Sex hormones induce insulin resistance in 3T3-L1 adipocytes by reducing cellular content of IRS proteins

Collison, M, Campbell, IW, Salt, IP, Dominiczak, AF, Connell, J, Lyall, H, and Gould, GW (2000) Sex hormones induce insulin resistance in 3T3-L1 adipocytes by reducing cellular content of IRS proteins. Diabetologia, 43 (11). pp. 1374-1380. ISSN 0012-186X (doi:10.1007/s001250051541)

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Abstract

Aim/hypothesis. Numerous studies have suggested a relation between sex hormones and insulin sensitivity but the ability of sex hormones to directly influence insulin action in peripheral tissues has not been investigated. Methods. We have examined the effects of estriol, estradiol and estrone on insulin action in cultured 3T3-L1 adipocytes, a useful model of adipocytes. Results. Treatment of these cells with each of these sex hormones resulted in a statistically significant reduction in the ability of insulin to stimulate glucose transport independently of a reduction in total cellular GLUT-4 content. This diminished ability of insulin to stimulate glucose transport was accompanied by a reduction in the total cellular content of insulin receptor substrates -1 and -2 and the p85 alpha subunit of phosphatidylinositol 3'-kinase. By contrast, cellular content of protein kinase B was unchanged by hormone treatment but the magnitude of insulin-stimulated kinase activity was statistically significantly reduced after incubation with each of the sex hormones tested. We have further shown that treatment of 3T3-L1 adipocytes with these hormones alters the subcellular distribution of insulin receptor substrate proteins such that the particulate and soluble pools of these proteins were differentially affected by hormone treatment. Conclusion/interpretation. These data show that sex hormones can directly induce a state of insulin resistance in 3T3-L1 adipocytes in culture. The mechanism of this defect seems to be at least in part due to decreased cellular content and altered subcellular distribution of insulin receptor substrate proteins which in turn results in a reduction in proximal insulin-stimulated signalling cascades.

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s):Gould, Prof Gwyn and Dominiczak, Prof Anna and Salt, Dr Ian and Connell, Prof John
Authors: Collison, M, Campbell, IW, Salt, IP, Dominiczak, AF, Connell, J, Lyall, H, and Gould, GW
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Diabetologia
ISSN:0012-186X

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