A5035872776- Diabetes Treatment and Management
- Receptor Mechanisms and Signaling
- Chemokine receptors and signaling
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Metabolism, Diabetes, and Cancer
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Viral-associated cancers and disorders
- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Regulation of Appetite and Obesity
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Neuroendocrine Tumor Research Advances
- Cholesterol and Lipid Metabolism
- Diabetes Management and Research
- Chemical Synthesis and Analysis
- Biochemical Analysis and Sensing Techniques
- Drug Transport and Resistance Mechanisms
- Carbohydrate Chemistry and Synthesis
University of Copenhagen
2016-2025
Synergy University
2022
Novo Nordisk Foundation
2017-2021
Novo Nordisk (Denmark)
2021
Gentofte Hospital
2018
University of Florida
2016
Columbus Oncology and Hematology Associates
2016
Leiden University
2014
University of Southern Denmark
2013
Millennium Engineering and Integration (United States)
2007
The chemokine receptors CXCR4 and CCR5 have recently been shown to act as coreceptors, in concert with CD4, for human immunodeficiency virus–type 1 (HIV-1) infection. RANTES other chemokines that interact block infection of peripheral blood mononuclear cell cultures inhibit primary macrophages inefficiently at best. If used treat HIV-1–infected individuals, these could fail influence HIV replication nonlymphocyte compartments while promoting unwanted inflammatory side effects. A derivative...
Kaposi's sarcoma-associated herpesvirus encodes a chemokine called vMIP-II. This protein displayed broader spectrum of receptor activities than any mammalian as it bound with high affinity to number both CC and CXC receptors. Binding vMIP-II, however, was not associated the normal, rapid mobilization calcium from intracellular stores; instead, blocked induced by endogenous chemokines. In freshly isolated human monocytes virally encoded vMIP-II acted potent efficient antagonist chemotaxis...
The chemokine receptor CXCR4 is required, together with CD4, for entry by some isolates of HIV-1, particularly those that emerge late in infection. use these viruses likely has profound effects on viral host range and correlates the evolution immunodeficiency. Stromal cell-derived factor-1 (SDF-1), ligand CXCR4, can inhibit infection CXCR4-dependent viruses. To understand mechanism this inhibition, we used a monoclonal antibody specific to analyze phorbol esters SDF-1 surface expression...
The colonic epithelium harbors a large number of endocrine cells, but little is known about the functions colon. However, high density glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells great interest because potential antidiabetic antiobesity effects GLP-1 PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate free acid receptors FFAR2 (GPR43) FFAR3 (GPR41), stimulating cells. We used isolated perfused rat colon as model...
Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clinical outcomes beyond those achieved by selective agonist. Therefore, we hypothesized integrated potency signaling properties provide unique pharmacological profile tailored improving broad metabolic control. Here, establish methodology calculating...
The intra-islet theory states that glucagon secretion is suppressed when insulin stimulated, but glucagon's role in paracrine regulation controversial. This study investigated functions of mice. We examined glucagon-induced using isolated perfused pancreata from wild-type, GLP-1 receptor (GLP-1R) knockout, diphtheria toxin-induced proglucagon knockdown, β cell-specific (Gcgr) and global Gcgr knockout (Gcgr−/−) found stimulates through both GLP-1R. Moreover, loss either or GLP-1R does not...
Dietary fat is thought to stimulate release of incretin hormones via activation fatty acid receptors in the intestine. However, dietary (triacylglycerol) digested 2-monoacylglycerol and acids. Activation G protein-coupled receptor 119 (GPR119) stimulates glucagon-like peptide-1 (GLP-1) from intestinal L-cells. We aimed investigate if 2-oleoyl glycerol (2OG) can activate GPR119 vitro GLP-1 secretion vivo.Agonist activity for various lipids was tested on transiently expressed human COS-7...
Bile acids (BAs) facilitate fat absorption and may play a role in glucose metabolism regulation, stimulating the secretion of gut hormones. The relative importance mechanisms involved BA-stimulated appetite regulating hormones from pancreas is not well described was purpose this study. effects bile on pancreatic studied rats compared to most nutritional secretagogue: glucose. molecular that underlie by isolated perfused rat mouse small intestine preparations supported immunohistochemistry,...
The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted postprandially contribute importantly to postprandial glucose tolerance. In this study, we assessed the individual combined contributions of endogenous GIP GLP-1 changes in glucoregulatory using novel receptor antagonist GIP(3-30)NH2 well-established exendin(9-39)NH2 During 4-h oral tolerance tests (75 g) with an ad libitum meal test, 18 healthy men received on four...
Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes
AMD3100 is a symmetric bicyclam, prototype non-peptide antagonist of the CXCR4 chemokine receptor. Mutational substitutions at 16 positions located in TM-III, -IV, -V, -VI, and -VII lining main ligand-binding pocket receptor identified three acid residues: Asp171 (AspIV:20), Asp262 (AspVI:23), Glu288 (GluVII:06) as interaction points for AMD3100. Molecular modeling suggests that one cyclam ring interacts with TM-IV, whereas other sandwiched between carboxylic groups from TM-VI -VII,...
The 7TM receptor, US28, encoded by human cytomegalovirus binds a broad spectrum of endogenous CC chemokines with sub‐nanomolar affinity as determined in homologous competition binding assays. We here find that US28 also recognizes the membrane‐associated CX 3 C chemokine, fractalkine, (IC 50 =0.42±0.09 nM). Importantly, although fractalkine could compete high against chemokines, secreted were only able to for radioactive very low affinity. It is concluded which known enhance cell‐cell fusion...
The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. study performed as a cohort crossover study. volunteers received either 10 mg or intravenous on two separate days. Blood samples were collected at different time points following administration short infusion, respectively. Plasma concentrations determined by RIA technique. Pharmacokinetic analyses "the method residuals" compartmental analysis. pharmacokinetic variables: k a, t 1/2 absorption,...
A truncated form of human glucose-dependent insulinotropic polypeptide (GIP), GIP(3-30)NH2, was recently identified as an antagonist the GIP receptor. This study examined ability GIP(3-30)NH2 to antagonize physiological actions in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism humans. Eight lean subjects were studied by measuring arteriovenous concentrations metabolites ATBF on three different occasions during hyperglycemic-hyperinsulinemic...
Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to presumed GIP antagonist, (Pro3)GIP, its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between rodent system.Transiently transfected COS-7 cells were assessed for cAMP accumulation upon stimulation assayed...