A5044094842- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diet, Metabolism, and Disease
- Lipoproteins and Cardiovascular Health
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Cancer, Lipids, and Metabolism
- Advanced Proteomics Techniques and Applications
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Protein Kinase Regulation and GTPase Signaling
- Lipid metabolism and biosynthesis
- Metabolism and Genetic Disorders
- Cardiovascular Function and Risk Factors
- Nutritional Studies and Diet
- Lipid metabolism and disorders
- Diabetes Treatment and Management
- Cardiovascular Disease and Adiposity
- Ovarian function and disorders
Paderborn University
2024-2025
Heinrich Heine University Düsseldorf
2015-2024
Deutsches Diabetes-Zentrum e.V.
2015-2024
German Center for Diabetes Research
2014-2024
Hochschule Düsseldorf University of Applied Sciences
2019-2023
University Hospital Heidelberg
2021
Heidelberg University
2021
Institut für Medizinische Informatik, Biometrie und Epidemiologie
2006
University of Cologne
1996-2005
Medical University of Graz
2005
The pathogenesis of fatty liver is not understood in detail, but lipid overflow as well de novo lipogenesis (DNL) seem to be the key points hepatocyte accumulation lipids. One transcription factor DNL sterol regulatory element-binding protein (SREBP)-1c. We generated mice with liver-specific over-expression mature human SREBP-1c under control albumin promoter and a enhancer (alb-SREBP-1c) analyze systemic perturbations caused by this distinct alteration. targets specific genes causes enzymes...
Nonalcoholic fatty liver disease is associated with hepatic insulin resistance and may result primarily from increased de novo lipogenesis (PRIM) or secondarily adipose tissue lipolysis (SEC). We studied mice hepatocyte- adipocyte-specific SREBP-1c overexpression as models of PRIM SEC. featured lipogenic gene expression in the tissue. Their selective, liver-specific was C18:1-diacylglycerol content protein kinase Cε translocation. SEC had decreased mediated by cholesterol responsive...
Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by severe deficiency the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective treat neonatal life-threatening manifestations and been cornerstone treatment for this disease. However, burdensome complications occur despite lifelong diet. For diseases, patient disease specific registry fundamental monitor lifespan pathology evaluate safety efficacy...
The classic sterol regulatory cis element (sre-1) in the LDL receptor promoter mediates binding protein (SREBP)-binding and effects of insulin platelet derived growth factor (PDGF). To elucidate whether SREBP-1a SREBP-2 play a direct role PDGF action, stable cell lines HepG2 deficient either SREBP-1 or were used. Transfection these cells with wild-type fragment low density lipoprotein (LDL) gene showed that significantly reduced both, SREBP-1-as well as SREBP-2-deficient cells. Insulin...
Transcription of the low density lipoprotein (LDL) receptor gene is regulated by intracellular cholesterol concentration, hormones, and growth factors. We studied mechanisms which insulin estradiol stimulate promoter activity LDL gene. Hormonal effects were analyzed in HepG2 cells after transient transfection with promotor reporter constructs. Successive 5' deletions fragment from -537 to +88 revealed sterol regulatory element 1 (SRE-1) between -65 -56 as an insulin- estradiol-sensitive...
Sterol regulatory element-binding protein (SREBP)-1a is a transcription factor sensing cellular cholesterol levels and integrating gene signals mediated by MAP kinase cascades. Here we report the identification of serine 117 in SREBP-1a as major phosphorylation site kinases Erk1/2. This was identified nanoelectrospray mass spectrometry peptide sequencing recombinant fusion proteins phosphorylated Erk1/2 <i>in vitro</i>. Serine verified vitro</i> mutagenesis. Mutation to alanine abolished...
The rs738409(G) single nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As recently described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether SNP differently hepatic lipid content (hepatocellular lipids [HCL]) insulin sensitivity recent-onset diabetes.A total 917 participants German Diabetes...
A novel clustering approach identified five subgroups of diabetes with distinct progression trajectories complications. We hypothesized that these differ in multiple biomarkers inflammation. Serum levels 74 inflammation were measured 414 individuals recent adult-onset from the German Diabetes Study (GDS) allocated to based on data-driven cluster analysis. Pairwise differences between for assessed generalized linear mixed models before (model 1) and after 2) adjustment variables. Participants...
•Hepatic lipids increase 2-fold in the early course of type 2 diabetes.•Patients with 1 diabetes do not develop steatosis first 5 years after diagnosis.•Adipose tissue mass and insulin resistance drive development steatosis.•Phosphorus metabolites decline due to low portal supply. Background & AimsNon-alcoholic fatty liver disease (NAFLD) is associated abnormal mitochondrial capacity. While oxidative capacity can be increased steatosis, hepatic ATP decreases long-standing diabetes. However,...
The transcription factor sterol regulatory element binding protein (SREBP)-2 plays a pivotal role in lipid metabolism. Previously, we have shown that the mature form of SREBP-2 is substrate Erk-mitogen-activated kinases (MAPK). aim present study was to identify Erk-specific phosphorylation sites. Using chemistry approach, could Ser-432 and Ser-455 as major Further characterization by electrophoretic mobility shift assay promoter reporter gene analyses revealed does not influence protein/DNA...
Insulin resistance reflects the inadequate insulin-mediated use of metabolites and predicts type 2 diabetes (T2D) but is also frequently seen in long-standing 1 (T1D) represents a major cardiovascular risk factor.We hypothesized that plasma metabolome profiles allow identification unique common early biomarkers insulin both types.Two hundred ninety-five were analyzed by mass spectrometry from patients prospective observational German Diabetes Study with T2D (n = 244) or T1D 127) known...
Although insulin resistance is known to underlie type 2 diabetes, its role in the development of 1 diabetes has been gaining increasing interest. In a model nonobese diabetic (NOD) mouse, we found that driven by lipid- and glucose-independent mechanisms already present liver prediabetic mice. Hepatic associated with transient rise mitochondrial respiration followed increased production lipid peroxides c-Jun N-terminal kinase activity. At onset adipose tissue lipolysis promotes myocellular...
Diabetes may feature impaired insulin kinetics, which could be aggravated by altered hepatic metabolism and glycemic control. Thus, we examined clearance its possible determinants in individuals with recent-onset diabetes.Participants of the German Study (GDS) type 1 diabetes (T1D) (n = 306), 2 (T2D) 489), or normal glucose tolerance (control [CON]) 167) underwent hyperinsulinemic-euglycemic clamps for assessment whole-body sensitivity (M value) (ICCLAMP). Insulin rates were further...
Background and Aims Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed to pre-specified patterns their associations with cardiovascular risk factors, kidney function, neuropathy among endotypes. Methods Results The cross-sectional analysis included 765 individuals recent-onset (67%) prevalent (33%) from German Diabetes Study (GDS) allocated into severe autoimmune (SAID, 35%), insulin-deficient (SIDD, 3%), insulin-resistant (SIRD,...
Abstract Objectives To investigate whether selective reduction of postchallenge hyperglycaemia influences acute endothelial dysfunction, a very early manifestation vascular disease, in patients with impaired glucose tolerance. Methods In randomized, double‐blind, placebo‐controlled, cross‐over study the effect 200‐mg acarbose was investigated 28 subjects diagnosed Flow‐mediated dilation (FMD) brachial artery determined as measure function before and 2 3 h after ingestion 100‐g saccharose....
Blood serum samples are the major source for clinical proteomics approaches, which aim to identify diagnostically relevant or treatment-response related proteins. But, presence of very high-abundance proteins and enormous dynamic range protein distribution hinders whole analysis. An innovative tool overcome these limitations, utilizes combinatorial hexapeptide ligand libraries (ProteoMiner). Here, we demonstrate that ProteoMiner can be used comparative quantitative analysis complex...
The transcription factor sterol regulatory element binding protein (SREBP)-1a plays a pivotal role in lipid metabolism. Using the SREBP-1a expressing human hepatoma cell line HepG2 we have shown previously that is phosphorylated at serine 117 by ERK-mitogen-activated kinases (MAPK). combination of biology and chemistry approach show also target other MAPK-families, i.e. c-JUN N-terminal (JNK) or p38 stress activated MAP kinases. Serine major phosphorylation site for JNK. In contrast to sites...
The transcription factor sterol regulatory element binding protein (SREBP)-1c plays a pivotal role in lipid metabolism. In this report we identified the main phosphorylation sites of MAPK-families, i.e. p38 stress-activated MAPK (p38), ERK-MAPK (ERK) or c-JUN N-terminal kinases (JNK) SREBP-1c. major p38, serine 39 and threonine 402, are identical to those recently splice-variant SREBP-1a. contrast, ERK JNK phosphorylate SREBP-1c at two sites, 81 93, instead one site Functional analyses...
Hepatic and myocardial ectopic lipid deposition has been associated with insulin resistance (IR) cardiovascular risk. Lipid overload promotes increased hepatic oxidative capacity, stress, impaired mitochondrial efficiency, driving the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that higher availability ischemia-induced cardiac dysfunction decreases efficiency. Mice adipose tissue–specific overexpression sterol element–binding protein 1c as model combined NAFLD-IR...