caa a22 4500 475773187 CHVBK 20180406123623.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1007/s001250051541 doi (NATIONALLICENCE)springer-10.1007/s001250051541 Sex hormones induce insulin resistance in 3T3-L1 adipocytes by reducing cellular content of IRS proteins [Elektronische Daten] [M. Collison, I. W. Campbell, I. P. Salt, A. F. Dominiczak, J. M. C. Connell, H. Lyall, G. W. Gould] 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 p85α 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. [Diabetologia (2000) 43: 1374-1380] Springer-Verlag Berlin Heidelberg, 2000 Keywords Estradiol, estrone, estriol, insulin resistance, IRS proteins nationallicence Collison M. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut Campbell I. W. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut Salt I. P. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut Dominiczak A. F. University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK, GB aut Connell J. M. C. University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK, GB aut Lyall H. University Department of Obstetrics and Gynaecology, 10 Alexandra Parade, Royal Infirmary, Glasgow, Scotland, UK, GB aut Gould G. W. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut https://doi.org/10.1007/s001250051541 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051541 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Collison M. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Campbell I. W. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Salt I. P. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Dominiczak A. F. University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Connell J. M. C. University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Lyall H. University Department of Obstetrics and Gynaecology, 10 Alexandra Parade, Royal Infirmary, Glasgow, Scotland, UK, GB aut NATIONALLICENCE 700 1- Gould G. W. Division of Biochemistry and Molecular Biology, Davidson Building, Institute of Biomedical and Life Sciences, University of Glasgow, Scotland, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer