Refine
Year of publication
- 2020 (68) (remove)
Document Type
- Article (68)
Language
- English (68)
Has Fulltext
- yes (68)
Is part of the Bibliography
- no (68)
Keywords
- - (65)
- motor rehabilitation (4)
- proteomics (4)
- stroke (4)
- Delphi study (3)
- Germany (3)
- asthma (3)
- cattle trade (3)
- clinical (3)
- epidemic model (3)
- flux analysis (3)
- modularity (3)
- network analysis (3)
- osmotic stress adaptation (3)
- outcome measures (3)
- polyhydroxybutyrate (PHB) (3)
- proline (3)
- reactive oxygen species (3)
- sepsis (3)
- stochastic block model (3)
- transcriptomics (3)
- IL-33 (2)
- NGS (2)
- allergy (2)
- climate change (2)
- 1-MT (1)
- 16S rDNA amplicon sequencing (1)
- 16S rRNA (1)
- 3,5-diiodothyronine (1)
- Alzheimer (1)
- Alzheimer's disease (1)
- B cell response (1)
- B cells (1)
- BDNF (brain-derived neurotrophic factor) (1)
- Baltic Sea (1)
- CASP (1)
- CD4 (1)
- CNS—central nervous system (1)
- COVID-19 (1)
- Clp proteolysis (1)
- DEB-model (1)
- ESBL – (1)
- Europe (1)
- FreeSurfer (1)
- HCM (1)
- HCMV (1)
- HMGB1 (1)
- Hsp27 (1)
- IDO (1)
- IDO1 (1)
- IL10 (1)
- IgG (1)
- IgM (1)
- K (1)
- KREC (1)
- KYNA (1)
- L-type Ca (1)
- LepB (1)
- MALDI-TOF (1)
- MALDI-TOF MS (1)
- MDSC (myeloid-derived suppressor cell) (1)
- MRSA (1)
- MRSA - Methicillin-resistant (1)
- McsB arginine kinase (1)
- MgsR activity (1)
- MgsR degradation (1)
- MiD51 (1)
- Mongolia (1)
- NGF (nerve growth factor) (1)
- NN414 (1)
- PID (1)
- PKD (1)
- ROS (1)
- RareScreen (1)
- SCID (1)
- SLC22A9 (1)
- SRM (1)
- ST1159 (1)
- ST2 (1)
- Sec-translocon (1)
- Ser/Thr kinases (1)
- SigB (1)
- SplD (1)
- T cell (1)
- TREC (1)
- Tg4-42 (1)
- YidC (1)
- absolute protein quantification (1)
- affective disorders (1)
- aging (1)
- airway inflammation (1)
- alamandine (1)
- alpha-toxin (1)
- amino polymer (1)
- anti-steatotic action (1)
- antibody-secreting cells (1)
- antimicrobial susceptibility testing (1)
- antisense RNA (1)
- aquatic snail (1)
- arginine phosphorylation (1)
- audiovisual integration (1)
- autophagy (1)
- biofilm (1)
- biomarker (1)
- biotechnology (1)
- bipolar disorder (1)
- blood culture (1)
- blue intensity (1)
- body mass index (1)
- bone erosion (1)
- boreal forest (1)
- brackish water system (1)
- brain plasticity (1)
- broad-sense heritability (1)
- bud burst (1)
- calcium ion signaling (1)
- carbapenamase (1)
- carbon allocation (1)
- caveolae (1)
- chemoluminescence immunoassay (1)
- chemotherapy (1)
- childhood (1)
- chronic stroke (1)
- climate-growth relationship (1)
- clonal trees (1)
- coastal dunes (1)
- coffee metabolites (1)
- collagen-induced arthritis (1)
- competition (1)
- computational simulation (1)
- congenital hyperinsulinism (1)
- constant therapy (1)
- cross-reactivity (1)
- cross-sectional (1)
- dancers (1)
- deiodinase (1)
- dementia (1)
- dengue virus (1)
- diabetes mellitus (1)
- diazoxide (1)
- diffusion tension imaging (DTI) (1)
- dinutuximab beta (1)
- direct-on-target microdroplet growth assay (1)
- disturbance (1)
- dormancy induction (1)
- dormancy level (1)
- dormancy release (1)
- eddy covariance (1)
- emotion recognition (1)
- empathetic concern (1)
- empathy (1)
- environmental epidemiology (1)
- epigenome (1)
- epithelial-to-mesenchymal transition (1)
- estrone sulfate transporter (1)
- evidence (1)
- exacerbation (1)
- experimental stroke (1)
- extreme warming events (1)
- food spoilers (1)
- forest ecosystem research (1)
- forest growth-trends (1)
- forest inventory (1)
- functional magnetic resonance imaging (1)
- functional traits (1)
- funding priorities (1)
- genome (1)
- genomics (1)
- glucose metabolism (1)
- granulocyte subpopulation (1)
- group A streptococcus (1)
- growth rates (1)
- guideline (1)
- hand function (1)
- healtcare (1)
- heartbeat detection (1)
- hippocampal subfields (1)
- human association studies (1)
- human osteoblasts (1)
- hypertension (1)
- hypothyroidism (1)
- immune alterations (1)
- immune response (1)
- immune suppression (1)
- immunology (1)
- immunotherapy (1)
- infection (1)
- infection prevention (1)
- inflammasome (1)
- innate immune response (1)
- innate lymphoid cells (1)
- instrumentality of harm (1)
- interleukin 2 (1)
- interoception (1)
- ischemic stroke (1)
- kINPen (1)
- knowledge (1)
- kynurenine pathway (1)
- label-free quantification (1)
- latent class analysis (1)
- light intensity (irradiance) (1)
- light variability (1)
- low and mid income countries (1)
- machine learning (1)
- magnetic resonance imaging (1)
- manganese (1)
- mass spectometry (1)
- mass spectrometry (1)
- mathematical model (1)
- membrane proteins (1)
- metabolic syndrome (1)
- metabolism (1)
- metabolome (1)
- miRNA transcriptome (1)
- miRNA-Seq (1)
- microbiome (1)
- microbiota (1)
- microsite (1)
- mindreading (1)
- mitochondria (1)
- mitochondrial dynamics (1)
- mitochondrial fission (1)
- mitophagy (1)
- monocyte subpopulation (1)
- moral dilemmas (1)
- moral judgment (1)
- motor evoked potentials (1)
- motor function (1)
- musicians (1)
- mussel cultivation (1)
- navigation (1)
- neuroblastoma (1)
- neuronal plasticity (1)
- neurotrophic factors (1)
- newborn screening (1)
- nutrient supply (1)
- obesity (1)
- osmostress protectants (1)
- osteoporosis (1)
- oxidation-specific epitopes (1)
- oxidative dysbalance (1)
- pancreatic beta cells (1)
- parietal lobe (1)
- pathogenicity (1)
- peptide sharing (1)
- periodontal therapy (1)
- periplasm (1)
- perivascular adipose tissue (1)
- personal force (1)
- perspective taking (1)
- phosphatases (1)
- phosphopeptide enrichment (1)
- phosphoproteomics (1)
- photosynthetic rate (1)
- phytoplankton communities (1)
- pigment composition (1)
- planctomycetes (1)
- plasma medicine (1)
- plasma sources (1)
- polyelectrolyte multilayer (1)
- polymicrobial sepsis (1)
- polyreactive antibodies (1)
- potential natural vegetation (1)
- prediabetes (1)
- pregnancy (1)
- preterm birth (1)
- primary motor cortex (1)
- process dissociation procedure (1)
- profitability (1)
- protein production (1)
- proteome (1)
- psycho-physiological interaction (1)
- public health (1)
- rapid testing (1)
- reappraisal (1)
- recombinant protein (1)
- redox (1)
- regulatory monocytes (1)
- rehabilitation (1)
- renal denervation (1)
- research (1)
- resistance detection (1)
- resource availability (1)
- resource competition (1)
- rheumatoid arthritis (1)
- ring-width (1)
- risk communication (1)
- robot therapy (1)
- sample bias (1)
- schizophrenia (1)
- seizure (1)
- sensorimotor (1)
- septic arthritis (1)
- sex differences (1)
- sex steroids (1)
- shotgun-proteomics (1)
- smoking (1)
- social anxiety disorder (1)
- solid tumor models (1)
- spatial clustering (1)
- spatial representation (1)
- spatial transformation (1)
- spectral library (1)
- splenectomy (1)
- stand density (1)
- stiffness (1)
- stigma (1)
- stress response (1)
- stressors (1)
- stroke outcome (1)
- stroke rehabilitation (1)
- superior temporal sulcus (1)
- suppression (1)
- surface charge (1)
- susceptibility testing (1)
- systemic antibiotics (1)
- tDCS (1)
- targeted therapy (1)
- temperature adaptation (1)
- template magnetic resonance images (1)
- temporal variability (1)
- temporal voice area (1)
- thyroid hormone (1)
- titanium surface modification (1)
- titin (1)
- tolerance (1)
- toxicity (1)
- tractography (1)
- training (1)
- transcranial magnetic stimulation (1)
- transgenic mouse model (1)
- treatment tolerance (1)
- tree-rings (1)
- treeline (1)
- trees (1)
- tryptophan (1)
- tryptophan metabolites (1)
- type 2 immunity (1)
- virus replication (1)
- warm pulses (1)
- wettability (1)
- white matter integrity (1)
- white spruce (1)
- wild birds (1)
- xylem anatomy (1)
- zeta potential (1)
- γδ T cells (1)
Institute
- Klinik und Poliklinik für Neurologie (9)
- Abteilung für Mikrobiologie und Molekularbiologie (7)
- Institut für Botanik und Landschaftsökologie & Botanischer Garten (5)
- Institut für Immunologie u. Transfusionsmedizin - Abteilung Immunologie (5)
- Institut für Psychologie (4)
- Institut für Klinische Chemie und Laboratoriumsmedizin (3)
- Institut für Med. Biochemie u. Molekularbiologie (3)
- Institut für Mikrobiologie - Abteilung für Genetik & Biochemie (3)
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung (MNF) (3)
- Friedrich-Loeffler-Institut für Medizinische Mikrobiologie (2)
Publisher
- Frontiers Media S.A. (68) (remove)
Dengue virus (DV) is a positive-strand RNA virus of the Flavivirus genus. It is one of the most prevalent mosquito-borne viruses, infecting globally 390 million individuals per year. The clinical spectrum of DV infection ranges from an asymptomatic course to severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter because of severe plasma leakage. Given that the outcome of infection is likely determined by the kinetics of viral replication and the antiviral host cell immune response (HIR) it is of importance to understand the interaction between these two parameters. In this study, we use mathematical modeling to characterize and understand the complex interplay between intracellular DV replication and the host cells' defense mechanisms. We first measured viral RNA, viral protein, and virus particle production in Huh7 cells, which exhibit a notoriously weak intrinsic antiviral response. Based on these measurements, we developed a detailed intracellular DV replication model. We then measured replication in IFN competent A549 cells and used this data to couple the replication model with a model describing IFN activation and production of IFN stimulated genes (ISGs), as well as their interplay with DV replication. By comparing the cell line specific DV replication, we found that host factors involved in replication complex formation and virus particle production are crucial for replication efficiency. Regarding possible modes of action of the HIR, our model fits suggest that the HIR mainly affects DV RNA translation initiation, cytosolic DV RNA degradation, and naïve cell infection. We further analyzed the potential of direct acting antiviral drugs targeting different processes of the DV lifecycle in silico and found that targeting RNA synthesis and virus assembly and release are the most promising anti-DV drug targets.
Over the past 10 years, the crisis of sepsis has remained a great challenge. According to data from 2016, the sepsis-related mortality rate remains high. In addition, sepsis consumes extensive medical resources in intensive care units, and anti-inflammatory agents fail to improve sepsis-associated hyperinflammation and symptoms of immunosuppression. The specific immune mechanism of sepsis remains to be elucidated. Reactive oxygen species (ROS) are triggered by energy metabolism and respiratory dysfunction in sepsis, which not only cause oxidative damage to tissues and organelles, but also directly and indirectly promote NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. NLRP3 inflammasomes enlarge the inflammatory response and trigger apoptosis of immune cells to exacerbate sepsis progression. Inhibiting the negative effects of ROS and NLRP3 inflammasomes therefore provides the possibility of reversing the excessive inflammation during sepsis. In this review, we describe the interaction of ROS and NLRP3 inflammasomes during sepsis, provide prevention strategies, and identify fields that need further study.
The Immunomodulator 1-Methyltryptophan Drives Tryptophan Catabolism Toward the Kynurenic Acid Branch
(2020)
Background: Animal model studies revealed that the application of 1-methyltryptophan (1-MT), a tryptophan (TRP) analog, surprisingly increased plasma levels of the TRP metabolite, kynurenic acid (KYNA). Under inflammatory conditions, KYNA has been shown to mediate various immunomodulatory effects. Therefore, the present study aims to confirm and clarify the effects of 1-MT on TRP metabolism in mice as well as in humans.
Methods: Splenocytes from Balb/C or indoleamine 2,3-dioxygenase knockout (IDO1−/−) mice or whole human blood were stimulated with 1-MT for 6, 24, or 36 h. C57BL/6 mice received 1-MT in drinking water for 5 days. Cell-free supernatants and plasma were analyzed for TRP and its metabolites by tandem mass spectrometry (MS/MS).
Results: 1-MT treatment induced an increase in TRP and its metabolite, KYNA in Balb/C, IDO−/− mice, and in human blood. Concurrently, the intermediate metabolite kynurenine (KYN), as well as the KYN/TRP ratio, were reduced after 1-MT treatment. The effects of 1-MT on TRP metabolites were similar after the in vivo application of 1-MT to C57BL/6 mice.
Conclusions: The data indicate that 1-MT induced an increase of KYNA ex vivo and in vivo confirming previously described results. Furthermore, the results of IDO−/− mice indicate that this effect seems not to be mediated by IDO1. Due to the proven immunomodulatory properties of KYNA, a shift toward this branch of the kynurenine pathway (KP) may be one potential mode of action by 1-MT and should be considered for further applications.
Inflammatory Joint Disease Is a Risk Factor for Streptococcal Sepsis and Septic Arthritis in Mice
(2020)
Septic arthritis is a medical emergency associated with high morbidity and mortality, yet hardly any novel advances exist for its clinical management. Despite septic arthritis being a global health burden, experimental data uncovering its etiopathogenesis remain scarce. In particular, any interplay between septic arthritis and preceding joint diseases are unknown as is the contribution of the synovial membrane to the onset of inflammation. Using C57BL/6 mice as a model to study sepsis, we discovered that Group A Streptococcus (GAS) – an important pathogen causing septic arthritis - was able to invade the articular microenvironment. Bacterial invasion resulted in the infiltration of immune cells and detrimental inflammation. In vitro infected fibroblast-like synoviocytes induced the expression of chemokines (Ccl2, Cxcl2), inflammatory cytokines (Tnf, Il6), and integrin ligands (ICAM-1, VCAM-1). Apart from orchestrating immune cell attraction and retention, synoviocytes also upregulated mediators impacting on bone remodeling (Rankl) and cartilage integrity (Mmp13). Using collagen-induced arthritis in DBA/1 × B10.Q F1 mice, we could show that an inflammatory joint disease exacerbated subsequent septic arthritis which was associated with an excessive release of cytokines and eicosanoids. Importantly, the severity of joint inflammation controlled the extent of bone erosions during septic arthritis. In order to ameliorate septic arthritis, our results suggest that targeting synoviocytes might be a promising approach when treating patients with inflammatory joint disease for sepsis.
Interleukin-33 (IL-33) is a mucosal alarmin belonging to the IL-1 cytokine family and is now recognized to have a key role in innate and adaptive immunity, contributing to tissue homeostasis and response to environmental stresses. In addition, IL-33 has also been shown to work as a positive regulator that initiates and maintains a Th2 immune response. In the context of pregnancy, it has been recently demonstrated that upon certain stress conditions, such as an infection induced inflammation, IL-33 is released from the uterine mucosa and triggers decidual B cells to produce anti-inflammatory molecules, which in turn restore immune homeostasis and prevents the development of preterm birth. In this study we therefore performed a detailed characterization of IL-33 receptor (Il1rl1 or ST2) expression in B cells during normal pregnancy, as well as in a mouse model of preterm birth. We observed that splenic B cells significantly up-regulate the expression of Il1rl1 during pregnancy and identified the B1 B cell population as the main ST2-expressing B cell subset. A further kinetic analysis showed that percentages of ST2-expressing B1 B cells are significantly augmented on days 12 and 14 of pregnancy, both in the spleen and peritoneal cavity of pregnant mice, and then drop toward the end of pregnancy to the levels observed in non-pregnant animals. Furthermore, using a mouse model of LPS-induced preterm birth, we demonstrated that not only are the percentages of ST2-expressing B1 B cells significantly enlarged in the spleen during the acute phase of preterm birth, but decidual B cells also significantly up-regulate ST2 expression as compared to term-pregnant mice. Overall, our results suggest a functional role of ST2 expression in B cells during pregnancy and reinforce the importance of the IL-33/ST2 axis in B cells as a critical mechanism to control inflammation-induced preterm birth.
Changes in the environment will alter the growth rate of trees and forests. Different disciplines assess such growth rates differently, for example, with tree-ring width data, forest inventories or with carbon-flux data from eddy covariance towers. Such data is used to quantify forests biomass increment, forest’s carbon sequestration or to reconstruct environmental variables before instrumental records. However, raw measurement data is typically not considered to be representative for the average growth rate of trees or forests. Depending on the research question, the effects of certain environmental variables or effects of tree and forest structure have to be removed first. It can be challenging to define and quantify a growth trend that can answer a specific research question because trees and forests grow and respond to environmental change in multiple ways simultaneously, for example, with altered radial increment, height growth, and stand density. Further challenges pose time-lagged feedback loops, for example, between height and radial increment or between stand density and radial increment. Generally, different environments will lead to different tree and forest structures, but because of tree’s longevity this adaptation to the new environment will take decades or even centuries. Consequently, there can be an offset between the present forest structure and what we term the potential natural forest (PNF): Similar to the potential natural vegetation (PNV), the PNF represents that forest that would develop under the current environmental conditions in the absence of human intervention. Because growth rates are affected by the tree and forest structure, growth-trend estimates will differ between the present and the potential forest. Consequently, if the legacy effects of the past are not of interest, the PNF is the theoretical baseline to correct and estimate growth trends.
Introduction: Following behavioral recommendations is key to successful containment of the COVID-19 pandemic. Therefore, it is important to identify causes and patterns of non-compliance in the population to further optimize risk and health communication.
Methods: A total of 157 participants [80% female; mean age = 27.82 years (SD = 11.01)] were surveyed regarding their intention to comply with behavioral recommendations issued by the German government. Latent class analysis examined patterns of compliance, and subsequent multinomial logistic regression models tested sociodemographic (age, gender, country of origin, level of education, region, and number of persons per household) and psychosocial (knowledge about preventive behaviors, risk perception, stigmatizing attitudes) predictors.
Results: Three latent classes were identified: high compliance (25%) with all recommendations; public compliance (51%), with high compliance regarding public but not personal behaviors; and low compliance (24%) with most recommendations. Compared to high compliance, low compliance was associated with male gender [relative risk ratio (RRR) = 0.08 (0.01; 0.85)], younger age [RRR = 0.72 (0.57; 0.93)], and lower public stigma [RRR = 0.21 (0.05; 0.88)]. Low compliers were also younger than public compliers [RRR = 0.76 (0.59; 0.98)].
Discussion: With 25% of the sample reporting full compliance, and 51% differing in terms of public and personal compliance, these findings challenge the sustainability of strict regulatory measures. Moreover, young males were most likely to express low compliance, stressing the need for selective health promotion efforts. Finally, the positive association between public stigma and compliance points to potential othering effects of stigma during a pandemic, but further longitudinal research is required to examine its impact on health and social processes throughout the pandemic.
Staphylococcus aureus (S. aureus) can secrete a broad range of virulence factors, among which staphylococcal serine protease-like proteins (Spls) have been identified as bacterial allergens. The S. aureus allergen serine protease-like protein D (SplD) induces allergic asthma in C57BL/6J mice through the IL-33/ST2 signaling axis. Analysis of C57BL/6J, C57BL/6N, CBA, DBA/2, and BALB/c mice treated with intratracheal applications of SplD allowed us to identify a frameshift mutation in the serine (or cysteine) peptidase inhibitor, clade A, and member 3I (Serpina3i) causing a truncated form of SERPINA3I in BALB/c, CBA, and DBA/2 mice. IL-33 is a key mediator of SplD-induced immunity and can be processed by proteases leading to its activation or degradation. Full-length SERPINA3I inhibits IL-33 degradation in vivo in the lungs of SplD-treated BALB/c mice and in vitro by direct inhibition of mMCP-4. Collectively, our results establish SERPINA3I as a regulator of IL-33 in the lungs following exposure to the bacterial allergen SplD, and that the asthma phenotypes of mouse strains may be strongly influenced by the observed frameshift mutation in Serpina3i. The analysis of this protease-serpin interaction network might help to identify predictive biomarkers for type-2 biased airway disease in individuals colonized by S. aureus.
Background: This randomized controlled trial investigated if uni- and bihemispheric transcranial direct current stimulation (tDCS) of the motor cortex can enhance the effects of visuo-motor grip force tracking task training and transfer to clinical assessments of upper extremity motor function.
Methods: In a randomized, double-blind, sham-controlled trial, 40 chronic stroke patients underwent 5 days of visuo-motor grip force tracking task training of the paretic hand with either unilateral or bilateral (N = 15/group) or placebo tDCS (N = 10). Immediate and long-term (3 months) effects on training outcome and motor recovery (Upper Extremity Fugl-Meyer, UE-FM, Wolf Motor Function Test, and WMFT) were investigated.
Results: Trained task performance significantly improved independently of tDCS in a curvilinear fashion. In the anodal stimulation group UE-FM scores were higher than in the sham group at day 5 (adjusted mean difference: 2.6, 95%CI: 0.6–4.5, p = 0.010) and at 3 months follow up (adjusted mean difference: 2.8, 95%CI: 0.8–4.7, p = 0.006). Neither training alone, nor the combination of training and tDCS improved WMFT performance.
Conclusions: Visuo-motor grip force tracking task training can facilitate recovery of upper extremity function. Only minimal add-on effects of anodal but not dual tDCS were observed.
Clinical Trial Registration: https://clinicaltrials.gov/ct2/results?recrs=&cond=&term=NCT01969097&cntry=&state=&city=&dist=, identifier: NCT01969097, retrospectively registered on 25/10/2013.
Objective
Congenital hyperinsulinism (CHI) is a rare disease characterized by persistent hypoglycemia as a result of inappropriate insulin secretion, which can lead to irreversible neurological defects in infants. Poor efficacy and strong adverse effects of the current medications impede successful treatment. The aim of the study was to investigate new approaches to silence β-cells and thus attenuate insulin secretion.
Research Design and Methods
In the scope of our research, we tested substances more selective and more potent than the gold standard diazoxide that also interact with neuroendocrine ATP-sensitive K+ (KATP) channels. Additionally, KATP channel-independent targets as Ca2+-activated K+ channels of intermediate conductance (KCa3.1) and L-type Ca2+ channels were investigated. Experiments were performed using human islet cell clusters isolated from tissue of CHI patients (histologically classified as pathological) and islet cell clusters obtained from C57BL/6N (WT) or SUR1 knockout (SUR1-/-) mice. The cytosolic Ca2+ concentration ([Ca2+]c) was used as a parameter for the pathway regulated by electrical activity and was determined by fura-2 fluorescence. The mitochondrial membrane potential (ΔΨ) was determined by rhodamine 123 fluorescence and single channel currents were measured by the patch-clamp technique.
Results
The selective KATP channel opener NN414 (5 µM) diminished [Ca2+]c in isolated human CHI islet cell clusters and WT mouse islet cell clusters stimulated with 10 mM glucose. In islet cell clusters lacking functional KATP channels (SUR1-/-) the drug was without effect. VU0071063 (30 µM), another KATP channel opener considered to be selective, lowered [Ca2+]c in human CHI islet cell clusters. The compound was also effective in islet cell clusters from SUR1-/- mice, showing that [Ca2+]c is influenced by additional effects besides KATP channels. Contrasting to NN414, the drug depolarized ΔΨ in murine islet cell clusters pointing to severe interference with mitochondrial metabolism. An opener of KCa3.1 channels, DCEBIO (100 µM), significantly decreased [Ca2+]c in SUR1-/- and human CHI islet cell clusters. To target L-type Ca2+ channels we tested two already approved drugs, dextromethorphan (DXM) and simvastatin. DXM (100 µM) efficiently diminished [Ca2+]c in stimulated human CHI islet cell clusters as well as in stimulated SUR1-/- islet cell clusters. Similar effects on [Ca2+]c were observed in experiments with simvastatin (7.2 µM).
Conclusions
NN414 seems to provide a good alternative to the currently used KATP channel opener diazoxide. Targeting KCa3.1 channels by channel openers or L-type Ca2+ channels by DXM or simvastatin might be valuable approaches for treatment of CHI caused by mutations of KATP channels not sensitive to KATP channel openers.