A5089470832- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Diabetes Treatment and Management
- Genetic Mapping and Diversity in Plants and Animals
- Peroxisome Proliferator-Activated Receptors
- Histone Deacetylase Inhibitors Research
- Genetic Associations and Epidemiology
- Diet, Metabolism, and Disease
- RNA modifications and cancer
- Diabetes and associated disorders
- Genetic and phenotypic traits in livestock
- Antifungal resistance and susceptibility
- Phytochemistry Medicinal Plant Applications
- Microfluidic and Bio-sensing Technologies
- Bioinformatics and Genomic Networks
- Agricultural and Food Sciences
- CRISPR and Genetic Engineering
- Environmental and biological studies
- Mitochondrial Function and Pathology
- Adipokines, Inflammation, and Metabolic Diseases
- Advanced Proteomics Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Lipid metabolism and biosynthesis
- Cholinesterase and Neurodegenerative Diseases
Deutsches Diabetes-Zentrum e.V.
2016-2025
Heinrich Heine University Düsseldorf
2016-2025
German Center for Diabetes Research
2018-2025
University of Bremen
2019
Universidade Federal de Santa Catarina
2015-2018
Universidade Regional Integrada do Alto Uruguai e das Missões
2013
Abstract The loss of functional insulin-producing β-cells is a hallmark diabetes. Mammalian sterile 20-like kinase 1 (MST1) key regulator pancreatic β-cell death and dysfunction; its deficiency restores normoglycemia. identification MST1 inhibitors represents promising approach for β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as potent inhibitor, which improves survival under multiple diabetogenic conditions in human...
Introduction Candida dubliniensis, a new species of that has been recovered from several sites in healthy people, associated with recurrent episodes oral candidiasis AIDS and HIV-positive patients. This is closely related to C. albicans. The enzymatic activity dubliniensis response oxidative stress interest for the development drugs combat dubliniensis. Methods Fluconazole- amphotericin B-resistant strains were generated as described by Fekete-Forgács et al. (2000). Superoxide dismutase...
Physical exercise training is associated with increased glucose uptake in skeletal muscle and improved glycemic control. HDAC5, a class IIa histone deacetylase, has been shown to regulate transcription of the insulin-responsive transporter GLUT4 cultured cells. In this study, we analyzed contribution HDAC5 transcriptional network beneficial effect contraction regular on metabolism.HDAC5 knockout mice (KO) wild-type (WT) littermates were trained for 8 weeks treadmills, metabolically...
The effect of 3β-hidroxihop-22(29)ene (3-BHO) on insulin and glucagon-like peptide 1 (GLP-1) secretion as well the mechanism action compound in pancreatic islet glucose homeostasis was investigated. data from vivo treatment show that 3-BHO significantly reduces hyperglycemia by increasing GLP-1 secretion, accumulating hepatic glycogen hyperglycemic rats. In rat β-cell, stimulates uptake, vesicles translocation to plasma membrane thus through involvement potassium channels (ATP-...
To explore the genetic determinants of obesity and Type 2 diabetes (T2D), German Center for Diabetes Research (DZD) conducted crossbreedings obese diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) obesity, 190 QTL diabetes-related traits 100 plasma metabolites outcross populations. A computational framework was...
Isoflavones widely distributed in plants prevent diabetes. This study investigated the vivo and vitro effect of 3',4'-dihydroxy-6″,6″,6″',6″'-tetramethylbis(pyrano[2″,3″:5,6::2″',3″':7,8]isoflavone (bis-pyrano prenyl isoflavone) on glucose homeostasis hyperglycemic rats. The ethyl acetate fraction from aerial parts Polygala molluginifolia that contain isoflavones was assayed tolerance, maltase activity protein glycation. isoflavone bis-pyrano isolated this homeostasis. action exhibits an...
Abstract To identify novel disease genes for type 2 diabetes (T2D) we generated two backcross populations of obese and diabetes-susceptible New Zealand Obese (NZO/HI) mice with the lean mouse strains 129P2/OlaHsd C3HeB/FeJ. Subsequent whole-genome linkage scans revealed 30 quantitative trait loci (QTL) T2D-associated traits. The strongest association blood glucose [12 cM, logarithm odds (LOD) 13.3] plasma insulin (17 LOD 4.8) was detected on proximal chromosome 7 (designated Nbg7p, NZO 7)...
The Rab guanosine triphosphatase–activating protein (RabGAP) TBC1D1 has been shown to be a key regulator of glucose and lipid metabolism in skeletal muscle. Its function pancreatic islets, however, is not yet fully understood. Here, we aimed clarify the specific impact on insulin secretion substrate use islets. We analyzed dynamics glucose-stimulated (GSIS) isolated islets from Tbc1d1-deficient (D1KO) mice. To further investigate underlying cellular mechanisms, conducted pharmacological...
To characterize the role and mechanism of action (2E)-N'-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide (BZD) on incretin secretion, glucose uptake in skeletal muscle α-glucosidase activity intestine, targets for homeostasis. It was assayed tolerance test (GTT) to analyze GLP-1 secretion DPP-4 enzyme vitro. In muscle, carried out by vitro experiments. The intestinal disaccharidases performed after vivo compound improved around 30%, 25%, 20% at 15, 30, 60 min, respectively potentiated...
Exercise training induces white adipose tissue (WAT) beiging and improves glucose homeostasis mitochondrial function in rodents. This could be relevant for type 2 diabetes humans, but the effect of physical fitness on subcutaneous WAT (scWAT) remains unclear. translational study investigates if scWAT associates with healthy humans recent-onset a voluntary running wheel intervention is sufficient to induce mice.Gene expression levels established markers were measured biopsies (n = 28) or...
Abstract Type 2 diabetes (T2D) has a strong genetic component. Most of the gene variants driving pathogenesis T2D seem to target pancreatic β-cell function. To identify novel acting at early stage disease, we analyzed whole transcriptome data differential expression (DE) and alternative exon splicing (AS) transcripts in islets collected from two metabolically diverse mouse strains 6 weeks age after three high-fat-diet intervention. Our analysis revealed 1218 DE 436 AS genes NZO/Hl vs...
The objective of this study was to investigate the effect and mechanism action fernenediol as an insulin secretagogue. Wistar rats were treated with 0.1, 1, 10 mg/kg before inducing hyperglycemia by oral glucose. glycaemia, insulin, LDH, calcium, hepatic glycogen analyzed. Considering intestine pancreas targets for triterpene action, duodenum used verify influence on intestinal glycosidases. Additionally, pancreatic islets studies 14C-deoxyglucose uptake influx 45Ca2+ in hyperglycemic media...
To nominate novel disease genes for obesity and type 2 diabetes (T2D), we recently generated two mouse backcross populations of the T2D-susceptible New Zealand Obese (NZO/HI) strain genetically different, lean T2D-resistant strains, 129P2/OlaHsd C3HeB/FeJ. Comparative linkage analysis our female identified seven body fat-associated quantitative trait loci (QTL). Only locus Nbw14 (NZO weight on chromosome 14) showed to obesity-related traits in both populations, indicating that causal gene...
Type 2 diabetes (T2D) represents a multifactorial metabolic disease with strong genetic predisposition. Despite elaborate efforts in identifying the variants determining individual susceptibility towards T2D, majority of factors driving development remain poorly understood. With aim to identify novel T2D risk genes we previously generated an N2 outcross population using two inbred mouse strains New Zealand obese (NZO) and C3HeB/FeJ (C3H). A linkage study performed this led identification...
Background: The identification of novel diabetes risk genes is an essential field for prevention and treatment the disease. Mouse models represent useful tools to investigate diabetes-genetics factors associated respective cellular function. In this project, a backcross between diabetes-susceptible New Zealand Obese (NZO) lean C3HeB/FeJ mice was performed in order identify potential new diabetes-inducing or -protective candidate genes.
Background Obesity represents a major risk factor for the development of insulin resistance and T2D but polygenic factors promoting obesity still remain to be identified. We conducted linkage analyses in backcross population generated with T2D- prone New Zealand Obese (NZO) lean C3HeB/FeJ mice detected quantitative trait locus on chromosome 4 (Nbw4) that conferred protection from high-fat diet (HFD)-induced obesity. The aim study is identify underlying genetic variants assess their molecular...
To identify new diabetes-associated genes we investigated an outcross population generated by crossbreeding of diabetes-susceptible New Zealand Obese (NZO) mice with the diabetes-resistant C3HeB/FeJ mouse strain.
This study took advantage of our previously detected Quantitative Trait Loci (QTL) for blood glucose identified on chromosomes 7 (designated Nbg7 p) and 15 Nbg15 d) in a backcross obese, diabetes-susceptible NZO with lean C3 H mice (Schallschmidt et al., Genetics 2018 210:1527). For both QTL, the H-alleles were associated lower but higher plasma-insulin levels, indicating protective function pancreatic β-cells which further investigated by genotype-specific morphology.
Muscle derived IL-6 secretion following exercise has been linked to improvements of insulin sensitivity and maintenance glucose hemostasis via its endocrine, autocrine paracrine roles. Recently, it reported that histone acetylation can regulate transcription but involvement in muscle was not completely known. Exercise mediated changes have inhibit HDAC5, a class IIa deacetylase. In this study, we analyzed the role HDAC5 stimulation.
Despite the relative success from Genome-wide association studies (GWAs), vast majority of genetic determinants associated with type 2 diabetes (T2D) in humans remain uncharacterized. For identification novel risk genes for obesity and T2D, a crossbreeding approach obese, diabetes-prone NZO lean diabetes-resistant 129P2 mice was conducted.