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Background
Insulin resistance is a hallmark of diabetes. Proper insulin action in adipose tissue is of utter importance for a healthy metabolism, as insulin regulates lipogenesis and protects against lipotoxic effects. Interestingly, diabetic patients exhibit decreased insulin receptor (IR) ex-pression in adipose tissue and lack IR expression in this tissue causes a lipodystrophy phenotype. Recently, we demonstrated that the trace element selenium regulates the expression of GPx3 and thereby controls IR expression in adipocytes. In addition, GPx3 positively correlates with IR expression in human adipose tissue. The aim of this thesis is to investigate the impact of GPx3 on insulin sensitivity in adipocytes and to identify a potential interaction of GPx3 with IR.
1. Downregulation of insulin receptors in obese man. Wigand JP, Blackard WG. Diabetes. 1979 Apr;28(4):287-91.
2. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function. Boucher J, et al., Diabetes. 2016 Aug;65(8):2201-13.
3. GPx3 dysregulation impacts adipose tissue insulin receptor expression and sensitivity. Hauffe R, et al., JCI Insight. 2020 Jun 4;5(11):136283.
Tasks:
We offer excellent working conditions in an interactive and multidisciplinary research environment.
If you are interested, please contact until 01.08.2020
Prof. Dr. André Kleinridders (andre.kleinriddersuuni-potsdampde)
University of Potsdam
Institute of Nutritional Science
Molecular and Experimental Nutritional Medicine
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
Potsdam, 15.06.2020
Background
Insulin action in the brain reduces food intake, improves metabolism and supports cognitive function. Brain insulin resistance is a hallmark of obese, diabetic patients. Increased food intake with high amounts of long chain fatty acids is sufficient to induce decreased insulin signaling in the central nervous system. Yet molecular causes for this observation are not fully understood. We have shown that palmitate stimulation is a causal factor for neuronal insulin resistance causing a reduction in insulin receptor phosphorylation. Thus, an elevated phosphatase activity might be responsible for palmitate-induced insulin resistance. The aim of this thesis is to investigate the interaction of an already identified phosphatase with the insulin receptor in neurons.
1. Interplay of Dietary Fatty Acids and Cholesterol Impacts Brain Mitochondria and Insulin Action. Schell M, Chudoba C et al., Nutrients. 2020 May 23;12(5):E1518
2. Insulin action in the brain regulates mitochondrial stress responses and reduces diet-induced weight gain. Wardelmann K, Blümel S, Rath M, et al., Mol Metab. 2019 Mar;21:68-81.
3. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders. A. Kleinridders et al., Proc Natl Acad Sci U S A 2015; 112, 3463-3468
4. Insulin action in brain regulates systemic metabolism and brain function. Kleinridders A, et al., Diabetes 2014; 63, 2232-2243
Tasks:
We offer excellent working conditions in an interactive and multidisciplinary research environment.
If you are interested, please contact until 01.08.2020
Prof. Dr. André Kleinridders (andre.kleinriddersuuni-potsdampde)
University of Potsdam
Institute of Nutritional Science
Molecular and Experimental Nutritional Medicine
Arthur-Scheunert-Allee 114-116
14558 Nuthetal
Potsdam, 15.06.2020
University of Potsdam
Molecular and Experimental Nutritional Medicine
Arthur-Scheunert.Alle 155
14558 Nuthetal
Tel.: +49 33200 88-5528
Fax: +49 33200 88-5573
E-Mail: idiesseluuni-potsdampde