A5064733533- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Diet and metabolism studies
- Liver Disease Diagnosis and Treatment
- Cellular transport and secretion
- Diabetes and associated disorders
- Cancer, Hypoxia, and Metabolism
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Exercise and Physiological Responses
- Diabetes Treatment and Management
- Advanced Proteomics Techniques and Applications
- Peroxisome Proliferator-Activated Receptors
- Protein Kinase Regulation and GTPase Signaling
- Genetic Mapping and Diversity in Plants and Animals
- Muscle metabolism and nutrition
- Metabolomics and Mass Spectrometry Studies
- Lipid metabolism and biosynthesis
- Genetic Associations and Epidemiology
- Cardiovascular Function and Risk Factors
- Cardiovascular Disease and Adiposity
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Regulation of Appetite and Obesity
Heinrich Heine University Düsseldorf
2016-2025
Deutsches Diabetes-Zentrum e.V.
2016-2025
German Center for Diabetes Research
2016-2025
Düsseldorf University Hospital
2023-2025
Hochschule Düsseldorf University of Applied Sciences
2022-2024
Helmholtz Zentrum München
2024
Universitätsklinikum Aachen
2020
Max Planck Institute of Immunobiology and Epigenetics
2018
Institute of Diabetes Research
2014
German Institute of Human Nutrition
2003-2013
OBJECTIVE We investigated whether metabolic biomarkers and single nucleotide polymorphisms (SNPs) improve diabetes prediction beyond age, anthropometry, lifestyle risk factors. RESEARCH DESIGN AND METHODS A case-cohort study within a prospective was designed. randomly selected subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were free at baseline. Of the 801 incident type 2 cases identified in cohort during 7 years follow-up, 579 remained for analyses after exclusions....
Intestinal vitamin C (Asc) absorption was believed to be mediated by the Na+-dependent ascorbic acid transporter SVCT1. However, Asc transport across intestines of SVCT1 knock-out mice is normal indicating that alternative mechanisms exist. To investigate these mechanisms, rodents were gavaged with or its oxidized form dehydroascorbic (DHA), and plasma concentrations measured. doubled following DHA but not gavage. We hypothesized transporters responsible facilitated glucose (GLUTs). Using...
The German Diabetes Study (GDS) is a prospective longitudinal cohort study describing the impact of subphenotypes on course disease. GDS aims at identifying prognostic factors and mechanisms underlying development related comorbidities.The comprises intensive phenotyping within 12 months after clinical diagnosis, 5-year intervals for 20 years annual telephone interviews in between. Dynamic tests, including glucagon, mixed meal, intravenous glucose tolerance hyperinsulinemic clamp serve to...
Muscle contraction during exercise is a major stimulus for the release of peptides and proteins (myokines) that are supposed to take part in beneficial adaptation exercise. We hypothesize application an vitro as electric pulse stimulation (EPS) human myotubes enables investigation molecular response clearly defined model. applied EPS 24 h primary studied whole genome-wide transcriptional well candidate myokines. observed 183 differentially regulated transcripts with fold changes >1.3. The...
Red blood cells (RBCs) influence rheology, and release ADP, ATP, nitric oxide, suggesting a role for RBCs in hemostasis thrombosis. Here, we provide evidence significant contribution of to thrombus formation. Anemic mice showed enhanced occlusion times upon injury the carotid artery. A small population was located platelet thrombi activation by direct cell contact via FasL/FasR (CD95) pathway known induce apoptosis. Activation platelets presence led FasL exposure that activated FasR on...
Exercise increases glucose uptake in skeletal muscle independently of insulin signaling. This makes exercise an effective stimulus to increase insulin-resistant muscle. AMPK has been suggested regulate during exercise/contraction, but findings from studies various transgenic animals have not reached consensus on this matter. Comparing methods used these reveals a hitherto unappreciated difference between those reporting role and that do not. led us test the hypothesis downstream target...
Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding complex network food intake energy balance regulation an essential prerequisite for pharmacological intervention obesity. G protein-coupled receptors (GPCRs) are among main modulators metabolism balance. They, instance, regulate appetite satiety in certain hypothalamic neurons, as well glucose lipid hormone secretion from adipocytes. Mutations some GPCRs, such...
The athlete’s paradox states that intramyocellular triglyceride accumulation associates with insulin resistance in sedentary but not endurance-trained humans. Underlying mechanisms and the role of muscle lipid distribution composition on glucose metabolism remain unclear. We compared highly trained athletes (ATHL) normal weight (LEAN) overweight-to-obese (OVWE) male female individuals. This observational study found ATHL show higher sensitivity, mitochondrial content, capacity, lower...
Dehydroascorbic acid (DHA), the first stable oxidation product of vitamin C, was transported by GLUT1 and GLUT3 in<i>Xenopus laevis</i> oocytes with transport rates similar to that 2-deoxyglucose (2-DG), but due inherent difficulties GLUT4 expression in it uncertain whether DHA (Rumsey, S. C., Kwon, O., Xu, G. W., Burant, C. F., Simpson, I., Levine, M. (1997) <i>J. Biol. Chem.</i>272, 18982–18989). We therefore studied 2-DG rat adipocytes, which express GLUT4. Without insulin, adipocytes...
The Rab-GTPase–activating proteins TBC1D1 and TBC1D4 (AS160) were previously shown to regulate GLUT4 translocation in response activation of AKT AMP-dependent kinase. However, knockout mice lacking either Tbc1d1 or Tbc1d4 displayed only partially impaired insulin-stimulated glucose uptake fat muscle tissue. aim this study was determine the impact combined inactivation on metabolism double-deficient (D1/4KO) mice. D1/4KO normal fasting concentrations but had reduced tolerance...
The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether is insulin well energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL)) and wild-type littermates were studied. Glucose tolerance, glucose utilization, hepatic production, tissue-specific insulin-mediated uptake determined. effect of insulin, AICAR, or contraction on transport studied...
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,...
Although uncoating of clathrin-coated vesicles is a key event in clathrin-mediated endocytosis it unclear what prevents pits before they pinch off to become vesicles. We have shown that the J-domain proteins auxilin and GAK are required for by Hsc70 vitro. In present study, we expressed cultured cells determine if this would block causing premature pits. found expression indeed inhibited endocytosis. However, with its mutated so no longer interacted also as did clathrin-assembly protein,...
The subcellular targeting of the two recently cloned novel mammalian glucose transporters, GLUT6 {previously referred to as GLUT9 [Doege, Bocianski, Joost and Schürmann (2000) Biochem. J. 350, 771–776]} GLUT8, was analysed by expression haemagglutinin (HA)-epitope-tagged GLUTs in transiently transfected primary rat adipose cells. Similar HA-GLUT4, both HA-GLUT6 HA-GLUT8, were retained intracellular compartments non-stimulated In contrast, mutation N-terminal dileucine motifs constructs led...
In the obesity-resistant SJL mouse strain, we previously identified a naturally occurring loss-of-function mutation in gene for Tbc1d1. Characterization of recombinant inbred mice that carried Tbc1d1(SJL) allele on C57BL/6J background indicated loss TBC1D1 protects from obesity, presumably by increasing use fat as energy source. To provide direct functional evidence an involvement substrate metabolism, generated and characterized conventional Tbc1d1 knockout mice. TBC1D1-deficient showed...
Enhanced activin A release from epicardial adipose tissue (EAT) has been linked to the development of cardiac dysfunction in type 2 diabetes (T2D). This study examined whether inhibition insulin action induced by adipokines cardiomyocytes can be ascribed alterations miRNA expression.Expression levels miRNAs were assessed real-time PCR primary adult rat (ARC) exposed conditioned media generated EAT biopsies (CM-EAT) patients with and without T2D. CM-EAT-T2D altered expression eight ARC vs....