A5085197434- Pancreatic function and diabetes
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Metabolism, Diabetes, and Cancer
- Growth Hormone and Insulin-like Growth Factors
- Diabetes Treatment and Management
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
- Diabetes Management and Research
- Regulation of Appetite and Obesity
- Diet, Metabolism, and Disease
- Bariatric Surgery and Outcomes
- Receptor Mechanisms and Signaling
- Birth, Development, and Health
- Inflammasome and immune disorders
- Cancer, Hypoxia, and Metabolism
- Hormonal Regulation and Hypertension
- Virus-based gene therapy research
- Gestational Diabetes Research and Management
- Ion Transport and Channel Regulation
- IL-33, ST2, and ILC Pathways
- Pharmacogenetics and Drug Metabolism
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Biochemical Analysis and Sensing Techniques
- Epigenetics and DNA Methylation
University of Basel
2014-2024
University Hospital of Basel
2015-2024
University of Zurich
1999-2010
Swiss Integrative Center for Human Health
2010
University Hospital of Zurich
1990-2009
Diabetes Australia
2007
Boston University
1986-1988
Howard Hughes Medical Institute
1986
Harvard University
1986
Massachusetts General Hospital
1986
Abstract Islets of patients with type 2 diabetes mellitus (T2DM) display features an inflammatory process including elevated levels the cytokine IL-1β, various chemokines, and macrophages. IL-1β is a master regulator inflammation, IL-1 receptor I (IL-1RI) blockage improves glycemia insulin secretion in humans T2DM high-fat-fed mice pointing to pivotal role IL-1RI activity intra-islet inflammation. Given association dyslipidemia T2DM, we tested whether free fatty acids (FFA) promote...
Elevated glucose levels impair islet function and survival, it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity.The objective was investigate mRNA in near-pure beta-cells patients with type 2 diabetes (T2DM) study the regulation by isolated human islets.Laser capture microdissection performed isolate from pancreas sections 10 diabetic donors nine controls, analyzed using gene arrays PCR. Cultured islets fluorescence-activated cell sorter-purified were...
Epidermal growth factor (EGF) receptor monomers and noncovalently associated dimers were isolated by sucrose density gradient centrifugation, their respective binding autophosphorylation activities determined. We find that are low-affinity receptors high-affinity receptors. In the absence of EGF, exhibit a 4-fold higher activity than do monomers. Addition EGF increases on an average 4.8-fold but has minimal effect dimers. Furthermore, shifts monomer-dimer equilibrium to dimer form. conclude...
Abstract Chronic inflammation impairs insulin secretion and sensitivity. β-cell dedifferentiation has recently been proposed as a mechanism underlying failure in T2D. Yet the effect of on identity T2D not studied. Therefore, we investigated whether pro-inflammatory cytokines induce anti-inflammatory treatments improve via redifferentiation. We observed that IL-1β, IL-6 TNFα promote cultured human mouse islets, with IL-1β being most potent one them. In particular, maintaining transcription...
Pancreatic α cells may process proglucagon not only to glucagon but also glucagon-like peptide-1 (GLP-1). However, the biological relevance of paracrine GLP-1 for β cell function remains unclear. We studied effects locally derived insulin secretagogues on and glucose homeostasis using mice with ablation cell-specific deficiency. Normally, intestinal compensates lack cell-derived GLP-1. upon aging metabolic stress, tolerance is impaired. This was partly rescued DPP-4 inhibitor sitagliptin,...
The initial cephalic phase of insulin secretion is mediated through the vagus nerve and not due to glycemic stimulation pancreatic β cells. Recently, IL-1β was shown stimulate postprandial secretion. Here, we describe that this incretin-like effect involves neuronal transmission. Furthermore, found release by originating from microglia. Moreover, activated induce regulated activity hypothalamus in response stimulation. Notably, impaired obesity, both mice humans, mice, dysregulated...
To evaluate the regulatory role of growth hormone (GH) and insulin on insulin-like factor I (IGF-I) mRNA levels, we employed primary rat hepatocytes. Cells were incubated for 16 h with 10 nM insulin, GH, or a combination thereof, IGF-I levels analyzed by Northern blotting. Insulin results in 2.5-fold GH 3.8-fold higher than hormone-free controls, had an additive effect (6.7-fold). The was constant at variable concentrations. Therefore, affect independently each other. half-maximal effective...
Treatment of the soluble insulin receptor from human placenta with 1.25 mM dithiothreitol and 75 Tris at pH 8.5 results in complete reduction interhalf disulfide bonds (class 1 disulfides) dissociation tetrameric into dimeric alpha beta form. The halves exhibit a reduced affinity for binding (Boni-Schnetzler, M., Rubin, J. B., Pilch, P. F. (1986) Biol. Chem. 261, 15281-15287). Kinetic experiments reveal that class disulfides is faster process than loss ligand, indicating events subsequent to...
Growth factor receptors for T lymphocytes, such as interleukin 2 and insulin, are present on activated but not resting lymphocytes. We sought to determine if insulin-like growth I (IGF-I) could act a human cells characterize its receptor cells. Recombinant IGF-I induced two separate functions. It was chemotactic increased incorporation of tritiated thymidine into both unactivated (resting) mitogen-activated High-affinity 125I-IGF-I binding saturable with an apparent Kd 1.2 +/- .6 X 10(-10) M...
Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but decreased islets from patients with T2D. The protective role of local IL-1Ra was investigated pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific knockout (KO) mice. Deletion cells, not myeloid resulted diminished expression. Myeloid cells were main source circulating obesity. βIL-1Ra KO mice had impaired insulin secretion, reduced...
Tetrameric insulin holoreceptor (alpha 2 beta 2) was reduced with dithiothreitol into alpha dimers such that they maintain up to 50% of binding at tracer ligand concentrations. Scatchard analysis revealed had a affinity for by factor 3-6 compared holoreceptor, whereas the maximum number high sites not affected. The can be separated from sucrose density gradient centrifugation, and hence, are associated noncovalent interactions. Insulin-dependent autophosphorylation isolated low ionic...