A5011163375- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Adipokines, Inflammation, and Metabolic Diseases
- Trace Elements in Health
- Dietary Effects on Health
- melanin and skin pigmentation
- Diet, Metabolism, and Disease
- Eating Disorders and Behaviors
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Chemokine receptors and signaling
- Ion channel regulation and function
- Pharmacology and Obesity Treatment
- Drug Transport and Resistance Mechanisms
- Gut microbiota and health
- Peptidase Inhibition and Analysis
University of Copenhagen
2016-2025
Novo Nordisk Foundation
2014-2025
Novo Nordisk (Denmark)
2018
Laboratory of Molecular Genetics
2016
St. Luke's-Roosevelt Hospital Center
2015
AGH University of Krakow
2015
Jagiellonian University
2015
Novo Nordisk Foundation Center for Basic Metabolic Research
2015
Columbia University
2015
Maj Institute of Pharmacology
2015
Abstract Ghrelin is a GH-releasing peptide that also has an important role as orexigenic hormone-stimulating food intake. By measuring inositol phosphate turnover or by using reporter assay for transcriptional activity controlled cAMP-responsive elements, the ghrelin receptor showed strong, ligand-independent signaling in transfected COS-7 human embryonic kidney 293 cells. and number of known nonpeptide GH secretagogues acted agonists stimulating further. In contrast, low potency antagonist,...
GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be for obestatin, a peptide derived from precursor. Here, we compare effect obestatin Zn(2+) on signal transduction and study food intake. Although stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well response element-dependent serum transcriptional activity in GPR39-expressing cells opposed mock-transfected cells, no reproducible obtained with cells. Moreover, specific...
GPR40 (FFAR1), a clinically proven anti-diabetes target, is Gq-coupled receptor for long chain fatty acids (LCFA) stimulating insulin secretion directly and mediating major part of the dietary triglyceride-induced incretins GLP-1 GIP. In phase-II studies agonist TAK-875 decreased blood glucose but surprisingly without incretins.Here we find that can signal through not only Gq IP3 also Gs cAMP when stimulated with certain agonists such as AM-1638 AM-5262 in contrast to endogenous LCFA ligands...
Three members of the ghrelin receptor family were characterized in parallel: receptor, neurotensin 2 and orphan GPR39. In transiently transfected COS-7 human embryonic kidney 293 cells, all three receptors displayed a high degree ligand-independent signaling activity. The structurally homologous motilin served as constitutively silent control; upon agonist stimulation, however, it signaled with similar efficacy to related receptors. constitutive activity through G<sub>q</sub>, phospholipase...
Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 placebo 4 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 microg kg(-1) (lower-dose) ghrelin; (upper-dose) ghrelin. Active total ghrelin, growth hormone (GH), insulin-like factor levels monitored at baseline (4-5 day 1), during treatment days, end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria cardiac examination) did not differ between...
The conserved tryptophan in position 13 of TM-VI (Trp-VI:13 or Trp-6.48) the CWXP motif located at bottom main ligand-binding pocket is believed to function as a rotameric microswitch activation process seven-transmembrane (7TM) receptors. Molecular dynamics simulations rhodopsin demonstrated that rotation around chi1 torsion angle Trp-VI:13 brings its side chain close equally highly Phe-V:13 (Phe-5.47) TM-V. In ghrelin receptor, engineering high affinity metal-ion sites between these...
The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, released together coact in the control of key metabolic target organs. However, recently, it became clear that several other can coexpressed intestinal-specific lineage enteroendocrine cells. Here, we focus on anatomical functional consequences coexpression neurotensin with GLP-1 PYY distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, triple...
Triglycerides (TGs) are among the most efficacious stimulators of incretin secretion; however, relative importance FFA1 (G Protein-coupled Receptor [GPR] 40), FFA4 (GPR120), and GPR119, which all recognize TG metabolites, ie, long-chain fatty acid 2-monoacylglycerol, respectively, is still unclear. Here, we find 3 receptors to be highly expressed enriched in fluorescence-activated cell sorting-purified GLP-1 GIP cells isolated from transgenic reporter mice. In vivo, TG-induced increase...
The gastric hormone ghrelin stimulates food intake and increases plasma glucose through activation of the growth secretagogue receptor (GHSR). Liver-expressed antimicrobial peptide 2 (LEAP2) has been proposed to inhibit actions inverse effects on GHSR activity. Here, we investigate exogenous LEAP2 postprandial metabolism ad libitum in a randomized, double-blind, placebo-controlled, crossover trial 20 healthy men. We report that infusion lowers concentrations decreases during an meal test. In...
Adaptor and scaffolding proteins determine the cellular targeting, spatial, thereby functional association of G protein-coupled seven-transmembrane receptors with co-receptors, transducers, downstream effectors adaptors post-signaling events such as receptor sequestration through interactions, mainly C-terminal intracellular tails receptors. A library from 59 representative members super family was probed glutathione S-transferase fusion for interactions four different adaptor previously...
Two nonpeptide (L692,429 and MK-677) two peptide [GH-releasing (GHRP)-6 ghrelin] agonists were compared in binding signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), serum-responsive (SRE) controlled transcription, as well arrestin mobilization. MK-677 acted a simple agonist having an affinity of 6.5 nm activated all systems with similar high potency (0.2-1.4 nm). L-692,429 also displayed very signaling assays (25-60 nm) but competed...
The receptor for the orexigenic peptide, ghrelin, is one of most constitutively active 7TM receptors known, as demonstrated under in vitro conditions. Change expression a associated with change signaling independent endogenous ligand. In following study, we found that ghrelin hypothalamus was up-regulated approximately 2-fold rats both during 48-h fasting and by streptozotocin-induced hyperphagia. separate experiment, to probe effect high basal vivo, used intracerebroventricular...
This study was undertaken to investigate the link between dietary fat content and intestinal levels of anorectic AŁacylethanolamines (NAEs), including oleoyleth-anolamide (OEA), palmitoylethanolamide (PEA), lino-leoylethanolamide (LEA). Male rats were fed high-fat diets (HFDs) with variable percentages [20–45% total energy (E%)] for 1–7 d;afterward, jejunums isolated, jejunal NAE measured by liquid-chromatography mass spectrometry. Enzyme activities mRNA expression two synthesizing enzymes,...
G protein-coupled receptor (GPR)-39 is a seven-transmembrane expressed mainly in endocrine and metabolic tissues that acts as Zn++ sensor signaling through the Gq G12/13 pathways. The expression of GPR39 regulated by hepatocyte nuclear factor (HNF)-1α HNF-4α, present study, we addressed importance for glucose homeostasis pancreatic islets function. localization were characterized pancreas cell lines. Gpr39(−/−) mice studied vivo, especially respect tolerance insulin sensitivity, vitro islet...
Zinc may act as a neurotransmitter in the central nervous system by activation of GPR39 metabotropic receptors.In present study, we investigated whether knockout would cause depressive-like and/or anxiety-like behavior, measured forced swim test, tail suspension and light/dark test. We also lack change levels cAMP response element-binding protein (CREB),brain-derived neurotrophic factor (BDNF) tropomyosin related kinase B (TrkB) hippocampus frontal cortex mice subjected to Western-blot...