BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation
| Autor: | Gina Dörpholz, Cory Thomas Lee, Karen Ruschke, Josef Köhrle, Nancy Schanze, Claus-Eric Ott, Petra Knaus, Isabelle Schreiber, Bjørt K Kragesteen, Stefan Mundlos |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures MAP Kinase Signaling System Glucose uptake medicine.medical_treatment lcsh:Medicine Bone Morphogenetic Protein 2 SMAD Carbohydrate metabolism Article Mice 03 medical and health sciences Insulin resistance Downregulation and upregulation 3T3-L1 Cells medicine Animals Humans lcsh:Science Glucose Transporter Type 4 Multidisciplinary biology Chemistry Insulin lcsh:R Biological Transport medicine.disease Up-Regulation Cell biology PPAR gamma Glucose 030104 developmental biology embryonic structures biology.protein lcsh:Q Insulin Resistance Rosiglitazone GLUT4 Signal Transduction medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-17595-5 |
| Popis: | 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: | OpenAIRE |
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