A5003018370- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Biochemical Analysis and Sensing Techniques
- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Cold Atom Physics and Bose-Einstein Condensates
- Neuropeptides and Animal Physiology
- Atomic and Molecular Physics
- Atomic and Subatomic Physics Research
- Advanced Frequency and Time Standards
- Cannabis and Cannabinoid Research
- Laser-induced spectroscopy and plasma
- MicroRNA in disease regulation
- nanoparticles nucleation surface interactions
- Genetic Syndromes and Imprinting
- Hippo pathway signaling and YAP/TAZ
- Ion Channels and Receptors
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics and Neurodevelopmental Disorders
- Apelin-related biomedical research
- Growth Hormone and Insulin-like Growth Factors
- Alcohol Consumption and Health Effects
Novo Nordisk (Denmark)
2021-2025
Novo Nordisk Foundation
2015-2022
University of Copenhagen
1977-2022
Johannes Gutenberg University Mainz
2019-2020
University of Applied Sciences Mainz
2019-2020
Singapore Bioimaging Consortium
2014-2015
Agency for Science, Technology and Research
2014-2015
Hubrecht Institute for Developmental Biology and Stem Cell Research
2013-2014
University Medical Center Utrecht
2014
Leiden University Medical Center
2011
Objective Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising fibres. Here, we investigated whether soluble dietary fibre oligofructose improves metabolism modulating bacterial transformation of secondary bile acids in mice fed western-style diet. Design To assess impact supplementation on acid bacteria, conventional wild-type TGR5 knockout diet enriched or not with cellulose oligofructose. In addition, used...
G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate activity through GPCRs. However, types GPCRs expressed in are largely unknown. Here, we determined expression profile all mouse, with a special emphasis on those innervating tract. Using combination high-throughput quantitative PCR,...
Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing number. Here we present novel in vitro platform generate functional from three-dimensional cultures mouse human intestinal crypts. We show that short-chain fatty acids selectively increase the number cells, resulting an elevation This is accompanied by upregulation...
Significance The present study shows that glucagon-like peptide-1 (GLP-1) potentiates insulin release by inducing the PKA-mediated phosphorylation of synaptotagmin-7 in pancreatic β-cells, thereby documenting hormone GLP-1 acts directly enhancing Ca 2+ -triggered exocytosis. PKA phosphorylates at a single serine residue linker between transmembrane region and its C-terminal C 2 domains bind ; accordingly, enhances secretion without changing dependence secretion. documents efficacy...
Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion L-cell abundance. Here we identify G-protein–coupled bile acid receptor (GPBAR1) as a selective regulator intestinal differentiation. Lithocholic the synthetic GPBAR1 agonist, L3740, selectively increased density mouse human organoids elevated secretory capacity. L3740 induced expression Gcg transcription factors...
In the stomach, somatostatin (SST) acts as a general paracrine negative regulator of exocrine secretion gastric acid and pepsinogen endocrine gastrin, ghrelin, histamine. Using reporter mice expressing red fluorescent protein (RFP) under control SST promotor, we have characterized G protein-coupled receptors expressed in Sst-RFP-positive cells probed their effects on primary cell cultures. Surprisingly, besides SST, amylin PYY were also highly enriched cells. Several found to regulate and/or...
Glucagon-like peptide-1–based (GLP-1–based) therapies improve glycemic control in patients with type 2 diabetes. While these agents augment insulin secretion, they do not mimic the physiological meal-related rise and fall of GLP-1 concentrations. Here, we tested hypothesis that increasing number intestinal L cells, which produce GLP-1, is an alternative strategy to responses glucose tolerance. Blocking NOTCH signaling pathway γ-secretase inhibitor dibenzazepine increased cells organoid–based...
GPR142, which is highly expressed in pancreatic islets, has recently been deorphanized as a receptor for aromatic amino acids; however, its physiological role and pharmacological potential unclear. We find that GPR142 not only β- but also α-cells of the islets well enteroendocrine cells, we confirm selective sensor essential acids, particular Trp oligopeptides with N-terminal Trp. knock-out mice displayed very limited metabolic phenotype demonstrated L-Trp induced secretion gut hormones...
Enteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake storage. Our goal is decipher gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied role transcription factor Rfx6 which had been identified as cause Mitchell–Riley syndrome, characterized by neonatal diabetes congenital malabsorptive diarrhea. We previously reported...
Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist and inverse agonist of the ghrelin receptor, countering ghrelin's effects on cell signaling feeding. However, despite emerging interest in LEAP2's physiology pharmacology, its endocrine regulation remains unclear. Here, we report that plasma LEAP2 levels decrease significantly upon glucagon infusions during somatostatin clamps humans. This effect preserved patients with obesity type diabetes while diminished...
Fatty acid amide hydrolase (FAAH) degrades 2 major classes of bioactive fatty amides, the N-acylethanolamines (NAEs) and N-acyl taurines (NATs), in central peripheral tissues. A functional polymorphism human FAAH gene is linked to obesity mice lacking show altered metabolic states, but whether these phenotypes are caused by elevations NAEs or NATs unknown. To overcome problem concurrent elevation genetic pharmacological disruption vivo, we developed an engineered mouse model harboring a...
Binding of ghrelin to its receptor, growth hormone secretagogue receptor (GHSR), stimulates GH release, induces eating, and increases blood glucose. These processes may also be influenced by constitutive (ghrelin-independent) GHSR activity, as suggested findings in short people with naturally occurring GHSR-A204E mutations reduced food intake glucose rodents administered inverse agonists, both which impair activity. In this study, we aimed more fully determine the physiologic relevance We...
Abstract Most metabolic studies on mice are performed at room temperature, although under these conditions mice, unlike humans, spend considerable energy to maintain core temperature. Here, we characterize the impact of housing temperature expenditure (EE), homeostasis and plasma concentrations appetite- glucoregulatory hormones in normal-weight diet-induced obese (DIO) C57BL/6J fed chow or 45% high-fat-diet, respectively. Mice were housed for 33 days 22, 25, 27.5, 30 °C an...
Micro-RNAs (miRNAs) are crucial for many biological processes, but their role in the enteroendocrine development and differentiation has been neglected due to elusive nature of cells. However, transgenic mice expressing fluorescent reporter proteins under control promoters Cck, Gpr41, Lgr5, ie, two different markers a marker stem cells, now enables identification FACS purification cells at stages along crypt-villus axis. Surprisingly few 746 analyzed miRNAs differed expression pattern...
GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known to be mainly expressed in the parathyroid gland and epididymis. This investigation aimed delineate cellular expression of GPR64 throughout body with focus on gastrointestinal (GI) tract.Transgenic Gpr64mCherry reporter mice were histologically examined protein intestinal tuft cells was confirmed by specific cell ablation. The GPCR repertoire Gpr64mCherry-positive analyzed quantitative RT-PCR analysis situ...
Evaluation of weight loss drugs is usually performed in diet-induced obese mice housed at ∼22°C. This a cold stress that increases energy expenditure by ∼35% compared to thermoneutrality (∼30°C), which may overestimate drug-induced loss. We investigated five anti-obesity mechanisms have been clinical development, comparing 22°C vs. 30°C. Glucagon-like peptide-1 (GLP-1), human fibroblast growth factor 21 (hFGF21), and melanocortin-4 receptor (MC4R) agonist induced similar losses. Peptide YY...
We report on spectroscopy of cold dysprosium atoms the $1001\text{\ensuremath{-}}\mathrm{nm}$ transition and present measurements excited-state lifetime which is at least $87(7)\phantom{\rule{4pt}{0ex}}\mathrm{ms}$ long. Due to long we are able measure ratio polarizability ground-state $1064\phantom{\rule{4pt}{0ex}}\mathrm{nm}$ be 0.83(0.13) by parametric heating in an optical dipole trap. In addition isotope shifts three most abundant bosonic isotopes with accuracy better than...
Obesity is a complex disease associated with high risk of comorbidities. Gastric bypass surgery, an invasive procedure low patient eligibility, currently the most effective intervention that achieves sustained weight loss. This beneficial effect attributed to alterations in gut hormone signaling. An attractive alternative pharmacologically mimic effects bariatric surgery by targeting several hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed gastrointestinal tract has been...
Restoring the control of food intake is key to obesity management and prevention. The arcuate nucleus (ARC) hypothalamus extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces by its action in Y (NPY) neurons hypothalamic ARC, but detailed mode observed human missing, due lack human-neuron-based model for pharmacology testing. Here, we validated utilized human-neural-stem-cell-based (hNSC) ARC test effects NPFF on cellular...
Rydberg-state excitations in ${\mathrm{Ne}}^{+}$, ${\mathrm{Mg}}^{+}$ -He collisions have been studied the projectile energy range 10-75 keV by means of optical spectrometry a search for systematic trends. The relative excitation cross sections levels Rydberg-term series are found to follow general ${({n}^{*})}^{p}$ behavior (${n}^{*}$ being effective quantum number) with $p\ensuremath{\lesssim}\ensuremath{-}3$ varying collision and particles, regardless whether excited-state population...
We report on sawtooth-wave adiabatic-passage (SWAP) slowing of bosonic and fermionic dysprosium isotopes by using a 136-kHz-wide transition at 626 nm. A beam precooled atoms is further decelerated in one dimension the SWAP force amount near zero velocity measured. demonstrate that can be twice as fast conventional optical molasses operated same transition. In addition, we investigate parameter range for which efficiently usable our setup relate results to adiabaticity condition. Furthermore,...