hrp0092p1-30 | Diabetes and Insulin | ESPE2019

Effects of Glypican-4 Protein on INS1E Cell Viability and Insulin Signalling

Buhl Joseph , Garten Antje , Richter Sandy , Kiess Wieland , Penke Melanie

Background: Glypican-4 is a heparan sulphate proteoglycan. In addition to a membrane-bound glypican-4, a soluble form exists. Human and rodent adipose tissue were identified as source of circulating glypican-4. Glypican-4 serum levels are associated with obesity and insulin resistance, as in type 2 diabetes (T2D). Because of its positive effect on insulin sensitivity, glypican-4 might play a role in the development of obesity, insulin resistance, and T2D. We a...

hrp0089fc6.3 | Fat, Metabolism and obesity | ESPE2018

Role of PTEN in the Proliferation and Differentiation of Preadipocytes

Kirstein Anna , Kassner Franziska , Schmid Gordian L. , Handel Norman , Penke Melanie , Kiess Wieland , Garten Antje

Background/aim: The PTEN hamartoma tumor syndrome (PHTS) is an overgrowth syndrome caused mainly by germline mutations in the tumor suppressor PTEN. Patients are predisposed for the development of malignant and benign tumors. Children and adolescents with PHTS frequently develop single or multiple lipomas. PTEN antagonizes the phosphatidylinositide3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway, which promotes proliferation and differentiation in ...

hrp0089p2-p170 | Fat, Metabolism and Obesity P2 | ESPE2018

Development of Resistance to Sorafenib, a Multikinase Inhibitor, in Hepatocellular Carcinoma is Mediated by SIRT

Garten Antje , Grohmann Theresa , Barnikol-Oettler Anja , Kluckova Katharina , Lavery Gareth , Kiess Wieland , Penke Melanie

Background/aim: Sorafenib® is a multi-kinase inhibitor and one of the few systemic treatment options for patients with advanced hepatocellular carcinomas (HCCs). Resistance to Sorafenib® develops frequently and could be mediated by the NAD dependent deacetylase sirtuin (SIRT) 1, a master regulator of cellular energy metabolism and stress responses. We aimed to find out if Sorafenib® treatment depends on changes in cellular NAD le...

hrp0086p2-p708 | Endocrinology and Multisystemic Diseases P2 | ESPE2016

Inhibition of NAMPT Increases the Sensitivity of Leukemia Cells for Etoposide

Gorski Theresa , Petzold-Quinque Stefanie , Richter Sandy , Schuster Susanne , Penke Melanie , Kiess Wieland , Garten Antje

Background: Cancer cells have a high NAD turnover rate due to their increased cell proliferation and DNA repair. Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the NAD salvage pathway, a regulator of the intracellular NAD pool and of the activity of Sirtuins (SIRTs), a class of NAD-dependent deacetylases.Objective and hypotheses: Cancer cells are highly dependent on NAD and are expected to be more susceptible to an inhibition of NAD ...

hrp0082lbp-d3-1007 | (1) | ESPE2014

Hepatic NAD Metabolism is Dysregulated by an Excessive Supply of Lipids

Kiess Wieland , Penke Melanie , Treebak Jonas T , Schuster Susanne , Gorski Theresa , Garten Antje

Background: Animal and human studies have shown that nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme of mammalian NAD biosynthesis from nicotinamide, is modified in non-alcoholic fatty liver disease. Here, we investigated the effect of a high fat diet on hepatic NAD metabolism in mice.Objective and hypotheses: A dysregulation of NAD metabolism is a pathogenic factor for the development of steatohepatitis (NASH).Metho...

hrp0089p2-p159 | Fat, Metabolism and Obesity P2 | ESPE2018

Serum NAMPT Levels are not Associated with Parameters of Liver Function in Children and Adolescents

Penke Melanie , Schuster Susanne , Dietz Yvonne , Garten Antje , Grafe Nico , Karlas Thomas , Wiegand Johannes , Korner Antje , Kiess Wieland

Background/Aim: Serum NAMPT (nicotinamide phosphoribosyltransferase) levels are altered in adult patients with non-alcoholic fatty liver disease (NAFLD). However, less is known about NAMPT serum levels children and adolescents and their association with parameters of liver function.Methods: Blood and anthropometric data of 416 children and adolescents who participated in the LIFE Child Study Leipzig were collected. Serum NAMPT (Adipogen) and cytokeratin-...

hrp0086lbp3 | (1) | ESPE2016

The Growth Hormone – Insulin Like Growth Factor I (IGF-1) System in Early Non-Alcoholic Fatty Liver Disease: From an Animal Model to a Children’s Cohort

de Giorgis Tommaso , Penke Melanie , Schuster Susanne , Grafe Nico , Kiel Alexander , Karlas Thomas , Weigand Johannes , Vogel Mandy , Garten Antje , Antje Korner , Kiess Wieland

Background: Non-alcoholic fatty liver disease (NAFLD) represents one of the most common obesity complications and can progress to non-alcoholic stetohepatitis (NASH). NASH is associated with lower insulin like growth factor I (IGF-1) and IGFBP-3, however no data are available regarding the growth hormone (GH)-IGF-I axis in early stage of NAFLD, characterised by hepatic steatosis.Objective and hypotheses: We aimed to investigate the GH-IGF-1 pathway in a ...