A5031280886- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Ion channel regulation and function
- Alzheimer's disease research and treatments
- Erythrocyte Function and Pathophysiology
- Connective Tissue Growth Factor Research
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Ion Transport and Channel Regulation
- Cellular transport and secretion
- Animal Virus Infections Studies
- Animal Disease Management and Epidemiology
- Vector-Borne Animal Diseases
- Viral Infections and Vectors
- Metabolism, Diabetes, and Cancer
- Cystic Fibrosis Research Advances
- Cerebrovascular and Carotid Artery Diseases
- Blood properties and coagulation
- Cardiovascular Disease and Adiposity
- MicroRNA in disease regulation
- Diabetes Treatment and Management
- Genetic Syndromes and Imprinting
- Supramolecular Self-Assembly in Materials
- Circular RNAs in diseases
Lund University
2019-2025
Abstract Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that secretion regulated by a circular RNA containing the lariat sequence second intron gene. Silencing this intronic in islets leads decrease expression key components secretory machinery β-cells, resulting impaired glucose- or KCl-induced and calcium signaling. The effect exerted at transcriptional level involves an interaction with RNA-binding protein TAR...
Glucose-induced insulin secretion depends on β-cell electrical activity. Inhibition of ATP-regulated potassium (KATP) channels is a key event in this process. However, KATP channel closure alone not sufficient to induce activity; activation depolarizing membrane current also required. Here we examine the role mechanosensor ion PIEZO1 Yoda1, specific agonist, activates small and thereby triggers activity with resultant stimulation Ca2+-influx secretion. Conversely, antagonist GsMTx4 reduces...
Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic β cells. To identify candidate genes contributing to T2D pathophysiology, we studied human islets approximately 300 individuals. We found 395 differentially expressed (DEGs) in individuals with T2D, including, our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the expression changes may predispose diabetes, as these associated HbA1c not diagnosed T2D....
Alzheimer's disease is a neurodegenerative condition which involves heavy neuronal cell death linked to oligomers formed during the aggregation process of amyloid
Abstract Type 2 diabetes is associated with cardiovascular disease, possibly due to impaired vascular fibrous repair. Yet, the mechanisms are elusive. Here, we investigate alterations in repair processes type atherosclerotic plaque extracellular matrix by combining multi-omics from human Carotid Plaque Imaging Project cohort and functional studies. Plaques patients have less collagen. Interestingly, lower levels of transforming growth factor-ß distinguish plaques and, these patients, markers...
Abstract Voltage-gated Ca 2+ (Ca V ) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, accessory ones, including gamma that remains unexplored. Here, we demonstrate 4 γ4) is downregulated islets from human donors with diabetes, diabetic Goto-Kakizaki (GK) rats, as well under conditions of gluco-/lipotoxic stress. Reduction γ4 expression results decreased L-type...
Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), disease caused by mutations in the transmembrane conductance regulator (CFTR). The cause of CFRD unclear, but commonly observed reduction first-phase insulin secretion suggests defects at beta cell level. Here we aimed to examine alpha and function Cftr tm1 EUR /F508del mouse model (C57BL/6J), which carries most human mutation CFTR , F508del mutation. expression, mass, granule...
Fluorescence-based single molecule techniques provide important tools towards understanding the molecular mechanism of complex neurodegenerative diseases. This requires efficient covalent attachment fluorophores. Here we create a series cysteine mutants (S8C, Y10C, S26C, V40C, and A42C) Aβ42, involved in Alzheimer's disease, based on exposed positions fibril structure label them with Alexa-fluorophores using maleimide chemistry. Direct stochastic optical reconstruction microscopy imaging...
SYT11 and SYT13, two calcium-insensitive synaptotagmins, are downregulated in islets from type 2 diabetic donors, but their function insulin secretion is unknown. To address this, we investigated the physiological role of these synaptotagmins insulin-secreting cells.Correlations between gene expression levels were performed using previously described RNA-seq data on 188 human donors. SiRNA knockdown was EndoC-βH1 INS-1 832/13 cells. Insulin measured with ELISA. Patch-clamp used for...
Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic β-cells and contributes the development of type-2 diabetes (T2D). The role low-voltage gated T-type CaV channels remains obscure. Here we have measured global expression CaV3.2 human islets found that gene CACNA1H, encoding CaV3.2, is negatively correlated with HbA1c donors, positively islet as well capacity isolated islets. Silencing or pharmacological blockade attenuates...
Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells neuronal elements. We have previously established insulinotropic actions of CART human rodent islets. The receptor for the beta unidentified. used RNA sequencing Cartpt knockdown (KD) INS-1 832/13 identified GPR162 as most Cartpt-regulated receptor. therefore tested if mediates effects cells. Binding to was using proximity ligation assay, radioactive binding, co-immunoprecipitation, KD Gpr162 mRNA...
Abstract Exocytosis in excitable cells is essential for their physiological functions. Although the exocytotic machinery controlling cellular secretion has been well investigated, function of vesicular cargo, i.e. secretory granular content remains obscure. Here we combine dSTORM imaging and single-domain insulin antibody, to dissect situ structure granule cores (IGCs) at nano level. We demonstrate that size shape IGCs can be regulated by juxta-granular molecules Nucleobindin-2 Enolase-1,...