Functional crosstalk of BMP and Insulin signaling within glucose metabolism of adipocytes

• Applicant: Professorin Dr. Petra Knaus, since 7/2015
• Subject Area: Endocrinology, Diabetology, Metabolism ; Biochemistry
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 231452680

Type 2 diabetes is a progressive metabolic disease characterized by hyperglycemia and reduced glucose uptake through the GLUT-4 transporter as a consequence of insulin resistance and a dysregulated insulin secretion. Type-2 diabetes patients with advanced malfunction of insulin producing beta cells are commonly treated with an insulin therapy, which further increases the insulin resistance in the skeletal musculature and in white adipose tissue. Therefore, the identification and development of alternative, insulin independent treatment pathways for the regulation of the cellular glucose uptake are of high relevance. In preliminary studies we have shown that the activation of the BMP signal cascade regulates the glucose homeostasis in adipocytes. A stimulation of 3T3-L1 adipocytes with BMP6 leads to an increase of glucose uptake via induction of GLUT-4 vesicle translocation. A combined BMP6/insulin treatment further increases the uptake of glucose significantly compared to insulin stimulation alone. For the first time, we have identified a protein-protein-interaction between factors of the BMP and insulin signal cascades and have proposed a molecular interplay between these two important signaling pathways. These findings suggest an insulin independent BMP6-induced functional interaction of the BMP- and insulin signal cascades, which translocates the GLUT-4 glucose transporter in adipocytes and thereby enhances the glucose uptake. The aims of this project are to elucidate i) which BMP receptors in adipocytes are involved in the BMP-induced glucose uptake, ii) if the identified protein interactions display a molecular and functional node in this process or iii) if further factors of the insulin cascade are regulated by an activated BMP signal cascade. Furthermore, potential alterations of the BMP and BMP receptor expressions in white adipose tissue will be investigated in insulin resistant mouse models to demonstrate both, the physiological and therapeutic relevance of the BMP pathway within the regulation of glucose homeostasis.

• DFG Programme: Research Grants
• Participating Person: Professor Matthias Blüher, Ph.D.
• Ehemalige Antragstellerin: Dr. Karen Ruschke, until 7/2015