Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension

Nature

Volumn 402, Issue 6764, 1999, Pages 880-883

  Barroso, I ^a   Gurnell, M ^b   Crowley, V E F ^b   Agostini, M ^b   Schwabe, J W ^c   Soos, M A ^b   Maslen, G Li ^a   Williams, T D M ^d   Lewis, H ^e   Schafer, A J ^a   Chatterjee, V K K ^b   O'Rahilly, S ^b  

^a Incyte Europe Ltd ^*  (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

^d PRINCE PHILIP HOSPITAL   (United Kingdom)

^e SELLY OAK HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; FATTY ACID; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; THIAZOLIDINE DERIVATIVE; TRIACYLGLYCEROL;

ADOLESCENT; ADULT; ARTICLE; CASE REPORT; CRYSTAL STRUCTURE; FEMALE; GENE MUTATION; GENETIC TRANSCRIPTION; GLUCOSE HOMEOSTASIS; HUMAN; HYPERTENSION; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIGAND BINDING; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; TRANSACTIVATION;

ADULT; ANIMALS; BENZOXAZOLES; BINDING SITES; DIABETES MELLITUS, TYPE 2; FEMALE; GENES, DOMINANT; HUMANS; HYPERTENSION; INSULIN RESISTANCE; LIGANDS; MALE; MICE; MIDDLE AGED; MODELS, MOLECULAR; MUTATION; NICOTINIC ACIDS; PHENYLPROPIONATES; PROTEIN CONFORMATION; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, RETINOIC ACID; RETINOID X RECEPTORS; TETRAHYDRONAPHTHALENES; THIAZOLES; THIAZOLIDINEDIONES; TRANSCRIPTION FACTORS;

MAMMALIA;

EID: 0033599038     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/47254     Document Type: Article

References (30)

1. Day, C. Thiazolidinediones: a new class of antidiabetic drugs. Diabetic Med. 16, 179-192 (1999).
2. Spiegelman, B. M. PPAR-γ: adipogenic regulator and thiazolidinedione receptor. Diabetes 47, 507-514 (1998).
3. Hattersley, A. T. Maturity onset diabetes of the young; clinical heterogeneity explained by genetic heterogeneity. Diabetic Med. 15, 15-24 (1998).
4. Flier, J. S. Syndromes of insulin resistance - from patient to gene and back again. Diabetes 41, 1207-1219 (1992).
5. Krook, A. et al. Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes 43, 357-368 (1994).
6. Whitehead, J. P. et al. Molecular scanning of the insulin receptor substrate I gene in subjects with severe insulin resistance. Diabetes 47, 837-639 (1998).
7. Tontonoz, P., Hu, E. & Spiegelman, B. M. Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor. Cell 79, 1147-1156 (1994).
8. Lehmann, J. M. et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J. Biol. Chem. 270, 12953-12956 (1995).
9. Willson, T. M. et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the anti-hyperglycemic activity of thiazolidinediones. J. Med. Chem. 39, 665-668 (1996).
10. Matthews, D. R. et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412-419 (1985).
11. Danielian, P. S., White, R., Lees, J. A. & Parker, M. G. Identification of a conserved region required for hormone dependent transcriptional activation by steroid hormone receptors. EMBO J. 11, 1025-1033 (1992).
12. Chakravarti, D. et al. Role of CBP/P300 in nuclear receptor signalling. Nature 383, 99-103 (1996).
13. Di Renzo, J. et al. Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators and corepressors. Mol. Cell. Biol. 17, 2166-2176 (1997).
14. Mukherjee, R. et al. Sensitization of diabetic and obese mice to insulin by retinoid X receptor agonists. Nature 386, 407-410 (1997).
15. Collingwood, T. N., Adams, M., Tone, Y. & Chatterjee, V. K. K. Spectrum of transcriptional dimerization and dominant negative properties of twenty different mutant thyroid hormone β receptors in thyroid hormone resistance syndrome. Mol. Endocrinol. 8, 1262-1277 (1994).
16. Desbois, C. et al. A novel mechanism of action for v-ErbA: abrogation of the inactivation of transcription factor AP-1 by retinoic acid and thyroid hormone receptors. Cell 67, 731-740 (1991).
17. Nolte, R. T. et al. Ligand binding and coactivator assembly of the peroxisome proliferator-activated receptor-γ. Nature 395, 137-143 (1998).
18. Ristow, M. et al. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. New Engl. J. Med. 339, 953-959 (1998).
19. Adams, M. et al. Transcriptional activation by peroxisome proliferator-activated receptor γ is inhibited by phosphorylation at a consensus mitogen-activated protein kinase site. J. Biol. Chem. 272, 5128-5132 (1997).
20. Beamer, B. A. et al. Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-γ2 gene with obesity in two Caucasian populations. Diabetes 47, 1806-1808 (1998).
21. Deeb, S. S. et al. A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet. 20, 284-287 (1998).
22. Sarraf, P. et al. Loss-of-function mutations in PPARγ associated with human colon cancer. Mol. Cell 3, 799-804 (1999).
23. Libby, P. et al. PPARγ activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARγ as a potential mediator in vascular disease. Arterioscler. Thromb. Vasc. Biol. 19, 546-551 (1999).
24. Iijima, K. et al. Expression of peroxisome proliferator-activated receptor γ (PPARγ) in rat aortic smooth muscle cells. Biochem. Biophys. Res. Comm. 247, 353-356 (1998).
25. Ogihara, T., Rakugi, H., Ikegama, H. et al. Enhancement of insulin sensitivity by troglitazone lowers blood pressure in diabetic hypertensives. Am. J. Hyperten. 8, 316-320 (1995).
26. Nakamura, Y. et al. Inhibitory action of insulin-sensitizing agents on calcium channels in smooth muscle cells from resistance arteries of guinea-pig. Br. J. Pharmacol. 123, 675-682 (1998).
27. Satoh, H. et al. Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: A new possible role of PPARγ on vascular endothelial function. Biochem. Biophys. Res. Comm. 254, 757-763 (1999).
28. Doi, K. et al. PPARγ modulates endothelial function: effects of thiazolidinediones on endothelial cell growth and secretion of endothelin (E1) and C-type natriuretic peptide (CNP). Circulation 98, 192 (1998).
29. Young, P. W. et al. Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor γ. J. Pharmacol. Exp. Ther. 284, 751-759 (1998).
30. Forman, B. M. et al. 15-Dexoy-delta 12, 14-prostaglandin 12 is a ligand for the adipocyte determination factor PPARγ. Cell 83, 803-812 (1995).