BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation.

Autor:	Schreiber I; Institute of Chemistry and Biochemistry - Biochemistry, Berlin, Germany.; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany., Dörpholz G; Institute of Chemistry and Biochemistry - Biochemistry, Berlin, Germany., Ott CE; Institute for Human Genetics and Medical Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany., Kragesteen B; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany.; Max Planck Institute for Molecular Genetics, Berlin, Germany., Schanze N; Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Lee CT; Institute of Chemistry and Biochemistry - Biochemistry, Berlin, Germany., Köhrle J; Institute for Experimental Endocrinology, Charité-Universitätsmedizin Berlin, Berlin, Germany., Mundlos S; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany.; Institute for Human Genetics and Medical Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Max Planck Institute for Molecular Genetics, Berlin, Germany., Ruschke K; Institute of Chemistry and Biochemistry - Biochemistry, Berlin, Germany., Knaus P; Institute of Chemistry and Biochemistry - Biochemistry, Berlin, Germany. knaus@chemie.fu-berlin.de.; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Berlin, Germany. knaus@chemie.fu-berlin.de.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2017 Dec 08; Vol. 7 (1), pp. 17192. Date of Electronic Publication: 2017 Dec 08.
DOI:	10.1038/s41598-017-17595-5
Abstrakt:	Insulin-resistance is the main cause of type 2 diabetes. Here we describe the identification and characterization of BMP2 and BMP6 as new insulin-sensitizing growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced insulin-mediated glucose uptake in both insulin-sensitive and -insensitive adipocytes. We exclude a direct effect of BMP2 or BMP6 on translocation of GLUT4 to the plasma membrane and demonstrate that these BMPs increase GLUT4 protein levels equipotent to Rosiglitazone. BMPs induce expression of PPARγ as the crucial mediator for the insulin-sensitizing effect. A comprehensive RNA-Seq analysis in mature adipocytes revealed regulation of both BMP/Smad and PPARγ target genes. The effects of BMP2 and BMP6 are not completely redundant and include regulation of genes involved in glucose and fatty acid metabolism and adipokine expression. Collectively, these findings suggest the BMP2 and BMP6 pathway(s) as promising new drug targets to treat insulin resistance.
Databáze:	MEDLINE
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