A5041828957- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Knowledge Management and Sharing
- Regulation of Appetite and Obesity
- Fibroblast Growth Factor Research
- Monoclonal and Polyclonal Antibodies Research
- Quality and Supply Management
- Microscopic Colitis
- Protein Kinase Regulation and GTPase Signaling
- Neuroscience and Neuropharmacology Research
- Pancreatic function and diabetes
- Lipid Membrane Structure and Behavior
- Organizational Learning and Leadership
- Chemical Synthesis and Analysis
- Neuroscience and Neural Engineering
- Service and Product Innovation
- IL-33, ST2, and ILC Pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Digital Marketing and Social Media
- Adipose Tissue and Metabolism
- Inflammatory Bowel Disease
- Education, Healthcare and Sociology Research
- Sustainable Supply Chain Management
- Innovation and Knowledge Management
- Neurobiology and Insect Physiology Research
Zealand Pharma (Denmark)
2022-2025
Copenhagen Business School
2023
Technical University of Denmark
2006-2021
Novo Nordisk (Denmark)
2010-2021
University of Manchester
2019
KU Leuven
2019
Shenzhen University
2019
Democritus University of Thrace
2019
Danfoss (China)
2012
Novo Nordisk (United Kingdom)
2011
The glucagon-like peptide (GLP)-1 receptor is a promising target for the treatment of type 2 diabetes and obesity, there great interest in characterizing pharmacology GLP-1 its ligands. In present report, we have applied bioluminescence resonance energy transfer assays to measure agonist-induced recruitment betaarrestins G-protein-coupled kinase (GRK) addition traditional measurements second messenger generation. hormone oxyntomodulin described literature as full agonist on glucagon...
Much evidence indicates that, during activation of seven-transmembrane (7TM) receptors, the intracellular segments transmembrane helices (TMs) move apart with large amplitude, rigid body movements especially TM-VI and TM-VII. In this study, AspIII:08 (Asp113), anchor point for monoamine binding in TM-III, was used as starting to engineer activating metal ion sites between extracellular beta2-adrenergic receptor. Cu(II) Zn(II) alone complex aromatic chelators acted potent (EC50 decreased 0.5...
Abstract In rodent models of type 2 diabetes (T2D), sustained remission hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as brain area responsible for this effect. To better understand cellular response to FGF1 in MBH, we sequenced >79,000 single-cell transcriptomes from diabetic Lep ob/ob mice obtained on Days 5 after icv either or vehicle. A wide range...
Peptides are notoriously known to display very short in vivo half-lives often measured minutes which many cases greatly reduces or eliminates sufficient efficacy. To obtain long allowing for up once-weekly dosing regimen, fatty acid acylation (lipidation) have been used non-covalently associate the peptide serum albumin thus serving as a circulating depot. This approach is generally considered scientific and patent community standard protract almost any given peptide. However, it not trivial...
This study has focused on enhancing the signal generated from interaction between a G-protein-coupled receptor (GPCR) and beta-arrestin 2 (beta-arr2), measured by bioluminescence resonance energy transfer (BRET(2)) technology. Both class A (beta(2)-adrenergic [beta(2)-AR]) B (neurokinin-type 1 [NK1-R]) GPCRs, classified based their internalization characteristics, have been analyzed. It was evaluated whether BRET(2) can be enhanced using (1) beta-arr2 phosphorylation-independent mutant...
To dissect the interaction between beta-arrestin ((beta)arr) and family B G protein-coupled receptors, we constructed fusion proteins glucagon-like peptide 1 receptor (beta)arr2. The constructs had an increase in apparent affinity selectively for glucagon, suggesting that (beta)arr2 locks a high-affinity conformation, which can be explored by some, but not all, ligands. adopted signaling phenotype governed tethered with attenuated protein-mediated cAMP signal higher maximal internalization...
We recently reported that in rodent models of type 2 diabetes (T2D), a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1) induces remission hyperglycemia is sustained for weeks. To clarify the peripheral mechanisms underlying this effect, we used Zucker diabetic fatty
Members of the family adenosine deaminases acting on RNA (ADARs) can catalyze hydrolytic deamination to inosine and thereby change sequence specific mRNAs with highly double-stranded structures. The ADARs all contain one or more repeats binding motif (DRBM). By both in vitro vivo assays, we show that DRBMs rat ADAR2 are necessary sufficient for dimerization enzyme. Bioluminescence resonance energy transfer (BRET) demonstrates also exists as dimers living mammalian cells mutation DRBM1 lowers...
In rodent models of type 2 diabetes (T2D), sustained remission diabetic hyperglycemia can be induced by a single intracerebroventricular (icv) injection fibroblast growth factor 1 (FGF1). To identify the brain areas responsible for this effect, we first used immunohistochemistry to map hypothalamic distribution phosphorylated extracellular signal–related kinase 1/2 (pERK1/2), marker mitogen-activated protein kinase–ERK signal transduction downstream FGF receptor activation. Twenty minutes...
Numerous studies have attested to the importance of extreme C terminus G protein α subunits in determining their selectivity receptor recognition. We previously reported that a highly conserved glycine residue within linker I is important for constraining fidelity recognition by Gα<sub>q</sub> proteins. Herein, we explored whether both modules (linker and terminus) interact cooperatively switching protein-coupled (GPCR)-to-effector specificity created as models mutant proteins which was...
Studies on rats have shown that lactic acid can improve excitability and function of depolarized muscles. The effect has been related to the ensuing reduction in intracellular pH causing inhibition muscle fibre Cl(-) channels. However, since several carboxylic acids with structural similarities lactate inhibit channels it is possible per se increase by exerting a direct these We therefore examined effects intact muscles skinned fibres together conductance (G(cl)). In where extracellular...
The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is largest family membrane-associated receptors. GPCRs are involved in pathophysiology numerous human diseases, and they constitute an estimated 30-40% all drug targets. During last two decades, GPCR oligomerization has been extensively studied using methods like bioluminescence resonance energy transfer (BRET) today, receptor-receptor interactions within a well-established phenomenon. Evidence impact on,...
In recent years peptide YY (PYY) has attracted attention within the area of diabetes and obesity due to its involvement in food intake regulation glucose homeostasis. It is well-known that PYY1-36 rapidly cleaved by dipeptidyl peptidase-4 more Y2 receptor selective analogue PYY3-36, which further inactive PYY3-34. order improve selectivity proteolytic stability C-terminus, we synthesized several analogues incorporating N-methyl amino acids or β-homo other non-natural acids. These were tested...
IL-22 facilitates mucosal healing by directly inducing epithelial regeneration and barrier integrity, which is essential for achieving remission thereby treating inflammatory bowel disease. Here, we evaluated efficacy of a novel lipidated alone in combination with immunomodulatory agents addressing chronic dextran sodium sulfate (DSS)-induced colitis mice demonstrated action on healing. Mice were treated DSS, followed various doses IL-22, anti-TNF antibody, fingolimod, or anti-mouse α4β7...
Several domains of G protein α subunits are implicated in the control receptor-G coupling specificity. Among these extreme N-and C-termini, α4/β6-loops, and loop linking N-terminal α-helix to β1-strand ras-like domain. In this study, we illustrate that single-point mutations a highly conserved glycine residue within linker I region Gα<sub>q</sub> subunit confers upon mutant ability be activated by Gα<sub>i</sub>- Gα<sub>s</sub> -coupled receptors, as evidenced guanosine...
Characterization of the GRKs participating in phosphorylation β2-adrenergic receptor (β2AR) have part been limited by lack a simple cell-free assay with membrane-bound β2AR and GRKs. We describe here for GRK postnuclear 600g fraction washed membranes intrinsic activity using phosphosite-specific antibody that recognizes pS(355,356). Treatment these preparations 1.0 μM isoproterenol (ISO) caused rapid maximal 10−15-fold increase site (t1/2 = 1 min) an EC50 ISO stimulation ∼80 nM. Extensively...
To analyze the interaction between neurokinin-1 (NK-1) receptor and G-protein coupled kinases (GRKs), we performed bioluminescence resonance energy transfer<sup>2</sup> (BRET<sup>2</sup>) measurements family A NK-1 GRK2 GRK5 as well their respective kinase-inactive mutants. We observed agonist induced of both with activated receptor. In saturation experiments, to interact in a monophasic manner while interacted biphasic low affinity phase corresponding for GRK5. Agonist was dependent on...
The signaling of seven transmembrane receptors/G-protein- coupled receptors (GPCRs) is regulated by a number receptor interacting proteins, including βarrestins (βarrs) and GPCR kinases (GRKs). In the present report, we have analyzed interaction pattern between glucagon-like peptide-1 (GLP-1) (GLP-1R), βarr2, GRK2 using bioluminescence resonance energy transfer assays. We found that βarr2 interacts with GLP-1R in biphasic manner phosphorylation-independent phosphorylation-dependent...
Purpose This paper aims to study the impact of intentionally developed communities practice (CoPs) on knowledge sharing and improvement in an administrative public sector organisation (PSO). Design/methodology/approach A case approach was used analyse CoPs by four different teams at a Danish PSO. The applied CoP development framework suggested literature develop CoPs. Findings Three out were successfully developed, they positively affected improvement. participants engaged conversations...
Communities of practice (CoPs) have been adopted by several industries, in particular healthcare, and researchers proposed explanatory frameworks guidelines for development. However, first‐line managers are left with sparse research‐based advice on how to develop CoP due a lack empirical studies from operations. In response, this paper proposes tests framework intentional development CoPs healthcare The is structured six steps, which incorporate seven factors as identified the literature. A...
The insulin receptor (IR) belongs to the tyrosine kinase super family and plays an important role in glucose homeostasis. interacts with several large docking proteins that mediate signaling from receptor, including substrate (IRS) Src homology-2-containing (Src). Here, we applied bioluminescence resonance energy transfer 2 (BRET2) technique study IR pathways. interaction between substrates IRS1, IRS4 Shc was examined response ligands different properties. association interacting partners...