A5060858987- Pancreatic function and diabetes
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Pancreatitis Pathology and Treatment
- Diabetes Treatment and Management
- Circadian rhythm and melatonin
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Genetics and Neurodevelopmental Disorders
- Birth, Development, and Health
- Air Quality and Health Impacts
- Amino Acid Enzymes and Metabolism
- DNA Repair Mechanisms
- Biomedical Research and Pathophysiology
- Gestational Diabetes Research and Management
- Digestive system and related health
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Inflammasome and immune disorders
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Immune cells in cancer
University of Basel
2017-2024
University Hospital of Basel
2011-2024
University Hospital of Zurich
2009-2024
VA Puget Sound Health Care System
2013-2020
University of Washington
2013-2020
Seattle University
2018
University of Zurich
2012-2015
University of Geneva
2013
University of Würzburg
2010-2011
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...
A low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL LDL play a role in regulation pancreatic islet cell apoptosis, proliferation, secretory function. Isolated mouse human islets were exposed to healthy donors. In murine beta-cells, decreased both proliferation maximal glucose-stimulated insulin secretion. The comparative analysis...
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...
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...
Abstract Defective insulin processing is associated with obesity and diabetes. Prohormone convertase 1/3 (PC1/3) an endopeptidase required for the of neurotransmitters hormones. PC1/3 deficiency genome-wide association studies relate early onset obesity. Here, we find that deletion in obesity-related neuronal cells expressing proopiomelanocortin mildly transiently change body weight fail to produce a phenotype when targeted Agouti-related peptide- or nestin-expressing tissues. In contrast,...
Abstract Aims/hypothesis Colony stimulating factor 1 (CSF1) promotes the proliferation, differentiation and survival of macrophages, which have been implicated in both beneficial detrimental effects on glucose metabolism. However, physiological role CSF1 signalling homeostasis potential therapeutic implications modulating this pathway are not known. We aimed to study composition tissue macrophages (and other immune cells) following receptor (CSF1R) inhibition elucidate metabolic consequences...
Abstract Background Air pollution has emerged as an unexpected risk factor for diabetes. However, the mechanism behind remains ill-defined. So far, lung been considered main target organ of air pollution. In contrast, gut received little scientific attention. Since particles can reach after mucociliary clearance from lungs and through contaminated food, our aim was to assess whether exposure deposition in or drive metabolic dysfunction mice. Methods To study effects versus exposure, we...
The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, also of human islet amyloid polypeptide (hIAPP), the peptide component amyloid, which cosecreted with insulin. Thus, treatment promote formation its associated toxicity. Conversely, metformin decreases by decreasing secretory demand could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin has been...
Aging is the prime risk factor for development of type 2 diabetes. We investigated role interleukin-1 (IL-1) system on insulin secretion in aged mice. During aging, expression protective IL-1 receptor antagonist decreased islets, whereas IL-1beta gene increased specifically CD45 + islet immune cell fraction. One-year-old mice with a whole-body knockout had higher vivo and isolated along enhanced proliferation marker Ki67 elevated size number islets. Myeloid cell-specific preserved...
Abstract The obesity epidemic continues to worsen worldwide. However, the mechanisms initiating glucose dysregulation in remain poorly understood. We assessed role that colonic macrophage subpopulations play homeostasis mice fed a high-fat diet (HFD). Concurrent with intolerance, pro-inflammatory/monocyte-derived macrophages increased HFD. A link between numbers and glycemia was established by pharmacological dose-dependent ablation of macrophages. In particular, colon-specific depletion...
Glutamate-induced cytotoxicity (excitotoxicity) has been detected in pancreatic beta cells. The cystine/glutamate antiporter System xc- exports glutamate to the extracellular space and is therefore implicated as driving excitotoxicity. As of yet, it not investigated whether contributes islet function.This study describes implications deficiency on glucose metabolism both constitutive myeloid cell-specific knockout mice using metabolic tests diet-induced obesity. Pancreatic islets were...
Abstract Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, underlying mechanisms remain unclear. Based on well documented role inflammation in type 2 diabetes, aim was to investigate GDM. We established a mouse model for GDM basis its two major risk factors, obesity and aging. In these mice, we observed increased Interleukin-1β (IL-1β) expression uterus placenta along elevated circulating IL-1β concentrations compared normoglycemic...