A5073563888- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Microfluidic and Capillary Electrophoresis Applications
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Adipose Tissue and Metabolism
- Cell Image Analysis Techniques
- Microfluidic and Bio-sensing Technologies
- Viral Infectious Diseases and Gene Expression in Insects
- Innovative Microfluidic and Catalytic Techniques Innovation
- CO2 Reduction Techniques and Catalysts
- Cannabis and Cannabinoid Research
- 3D Printing in Biomedical Research
- Electrohydrodynamics and Fluid Dynamics
- Erythrocyte Function and Pathophysiology
- RNA modifications and cancer
- Adenosine and Purinergic Signaling
- Neuroendocrine Tumor Research Advances
- Click Chemistry and Applications
Inspire
2016-2024
ETH Zurich
2015
During progression of type 2 diabetes, pancreatic β cells are subjected to sustained metabolic overload. We postulated that this state mediates a hypoxic phenotype driven by hypoxia-inducible factor-1α (HIF-1α) and treatment with the HIF-1α inhibitor PX-478 would improve cell function. Our studies showed protein was present in diabetic mouse models. In islets high glucose metabolism, emergence intracellular Ca2+ oscillations at low concentration abnormally basal release insulin were...
Insulin is released from pancreatic islets in a biphasic and pulsatile manner response to elevated glucose levels. This highly dynamic insulin release can be studied vitro with islet perifusion assays. Herein, novel platform perform glucose-stimulated secretion (GSIS) assays single presented for studying the dynamics of at high temporal resolution. A standardized human model developed microfluidic hanging-drop-based system engineered, which facilitates rapid switching, minimal sample...
Loss of pancreatic β-cell function is a critical event in the pathophysiology type 2 diabetes. However, studies its underlying mechanisms as well discovery novel targets and therapies have been hindered due to limitations available experimental models. In this study we exploited stable viability standardized human islet microtissues develop disease-relevant, scalable, reproducible model dysfunction by exposing them long-term glucotoxicity glucolipotoxicity. Moreover, establishing method for...
Abstract Aims/hypothesis In type 1 diabetes, the counterregulatory glucagon response to low plasma glucose is impaired. The resulting increased risk of hypoglycaemia necessitates novel strategies ameliorate alpha-cell impairment. Here, we aimed establish an in vitro model impairment diabetes using human islet microtissues (MTs) exposed proinflammatory cytokines. Additionally, investigated therapeutic potential incretin receptor agonists improving responses glucose. Methods Human MTs were...
Abstract The pro-inflammatory cytokines IFNα, IFNγ, IL-1β and TNFα may contribute to innate adaptive immune responses during islet inflammation (insulitis) in type 1 diabetes (T1D). We used deep RNA-sequencing analysis characterize the response of human pancreatic beta cells each cytokine individually compared signatures obtained with those present islets individuals affected by T1D. IFNα IFNγ had a much greater impact on cell transcriptome when TNFα. IFN-induced gene have strong correlation...
Type 1 diabetes is a heterogeneous group of disorders majorly characterized by autoimmune destruction pancreatic β-cells, resulting in absolute insulin deficiency. Current research models lack many functions critical for understanding the onset and progression this disease humans. Although isolated primary islets are considered standard tool research, their experimental use challenging due to inherent heterogeneity size, cellular composition purity, as well rapid decline functionality...
Modification of gene expression in pancreatic islets can be a powerful strategy for understanding the pathology diabetes and developing novel therapeutic strategies against it. However, amenability isolated to genetic manipulation has been limited only subset cells at periphery due poor penetration transduction particles. To address this issue, we developed standardized islet model, produced by optimized dissociation controlled scaffold-free reaggregation primary human cells. This process...
In 3D human islet microtissues from nondiabetic donors, pitolisant, a histamine 3 receptor antagonist, increased glucagon secretion >3-fold compared to vehicle control. However, the effect of pitolisant on was diminished in islets treated with cytokines, insulin, and low glucose mimic T1D hypoglycemia. The purpose this study determine if can restore impaired response hypoglycemia people T1D. double-blind randomized placebo-controlled five adults (3 2 placebo), 4 men, long-duration...
This experimental mouse study examined whether or not dedifferentiated β cells could be reversed targeted by pharmacological intervention for diabetes remission. They identified evidence β-cell dedifferentiation and dysfunction which single combined approaches.