Laboratory of Cell Signaling and Metabolic Disorders

Head: Agnieszka DOBRZYŃ

Staff: Anna Dziewulska (PhD student), Anna Gajda, Katarzyna Hanzelka, Justyna Janikiewicz, Magdalena Jazurek, Katarzyna Kolczyńska (PhD student), Kamil Koziński (PhD student), Katarzyna Maleńczyk (PhD student), Małgorzata Małodobra-Mazur, Katarzyna Mnich, Norbert Osiński (student), Aleksandra Pyrkowska, Aleksandra Rumińska (PhD student)

Research profile:

Our research group carries out multidisciplinary studies on signaling and transcriptional cascades that have far- reaching implications on cell metabolism and human metabolic diseases, mainly type 2 diabetes. The long-term goal of our research is to gain in-depth understanding of the functional interaction between transcription factors and obesity related disorders. Our main priority is to under- stand the role of lipid metabolites in the development of obesity-induced insulin resistance and beta-cell dysfunction. A second priority is to gain insights into the functional role of stearoyl-CoA desaturase (SCD) in the regulation of skeletal muscle, pancreatic islet and adipocyte metabolism because it will increase our understanding of how lipid partitioning is controlled, and may have important implications for pathogenesis of the Metabolic Syndrome

Methods:

• cellular and animal models of diabetes
• transfection/silencing of gene expression studies
• reporter gene assays
• real time PCR
• chromatography (TLC, HPLC, GC-MS)
• Western blot
• chromatin immunoprecipitation (ChIP)
DNA methylation
For more information see: http://team.nencki.gov.pl

Current research activities:

• identifying signaling pathways involved in the pathogenesis of insulin resistance and pancreatic beta-cell dysfunction in lipid-induced type 2 diabetes
• studies of transcription factors (FoxO1, TCF, STAT, PPAR, SREBP) as key molecules involved in lipotoxicity
• determining the role of metabolic and genetic abnormalities in endocannabinoid-related insulin resistance
• studies on epigenetic regulation of adipogenesis

Selected publications:

Dziewulska A., Dobrzyń P., Jazurek M., Pyrkowska A., Ntambi J.M, Dobrzyń A. (2012) Monounsaturated fatty acids are required for membrane translocation of protein kinase C-theta induced by lipid overload in skeletal muscle. Molecular Membrane Biology, 29: 309-320.

Dobrzyń P., Pyrkowska A., Jazurek M., Dobrzyń A. (2012) Increased availability of endogenous and dietary oleic acid contrib- utes to the upregulation of cardiac fatty acid oxidation. Mitochondrion 12: 132-137.

Dobrzyń P., Dobrzyń A., Miyazaki M., Ntambi J.M. (2010) Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice. Journal of Lipid Research, 51: 2202-2210.

Dobrzyń P., Jazurek M., Dobrzyń A. (2010) Stearoyl-CoA desaturase and insulin resistance – What is the molecular switch. Biochimica et Biophysica Acta, 1797: 1189-1194.

Dobrzyń P., Pyrkowska A., Jazurek M., Szymański K., Langfort J., Dobrzyń A. (2010) Endurance training-induced accumulation of muscle triglycerides is coupled to upregulation of stearoyl-CoA desaturase 1. Journal of Applied Physiology, 109: 1653-1661