A5044921536- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Immune Cell Function and Interaction
- Diet, Metabolism, and Disease
- Viral gastroenteritis research and epidemiology
- Pancreatitis Pathology and Treatment
- Celiac Disease Research and Management
- Immunodeficiency and Autoimmune Disorders
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Viral Infections and Immunology Research
- Endoplasmic Reticulum Stress and Disease
- Advanced Computational Techniques and Applications
- T-cell and B-cell Immunology
- Microscopic Colitis
- Inflammatory Bowel Disease
- Infant Nutrition and Health
- Parvovirus B19 Infection Studies
- Distributed and Parallel Computing Systems
- Gut microbiota and health
- Diabetes Treatment and Management
- Apelin-related biomedical research
- Metabolism, Diabetes, and Cancer
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
Uppsala University
2014-2024
Uppsala University Hospital
2009-2020
Pediatrics and Genetics
2013
The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at diagnosis of type 1 diabetes for presence viruses. Minimal tail resection was performed 3–9 weeks after onset in six adult patients (age 24–35 years). enteroviral capsid protein (VP1) and expression class I HLA were investigated by immunohistochemistry. Enterovirus RNA analyzed from isolated islets fresh-frozen whole using PCR sequencing. Nondiabetic organ donors served as controls. VP1 detected all...
A primary insult to the pancreatic islets of Langerhans, leading activation innate immunity, has been suggested as an important step in inflammatory process type 1 diabetes (T1D). The aim this study was examine whether interferon (IFN)-stimulated genes (ISGs) are overexpressed human T1D affected with insulitis. By using laser capture microdissection and a quantitative PCR array, 23 84 examined ISGs were found be by at least fivefold insulitic from living patients recent-onset T1D,...
The understanding of the etiology type 1 diabetes (T1D) remains limited. One objective Diabetes Virus Detection (DiViD) study was to collect pancreatic tissue from living subjects shortly after diagnosis T1D. Here we report insulin secretion ability by in vitro glucose perifusion and explore expression pathway genes isolated islets Langerhans these patients. Whole-genome RNA sequencing performed on six DiViD patients two organ donors who died at onset T1D, findings were compared with those...
The current view of type 1 diabetes (T1D) is that it an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing beta cells and cause overt diabetes. Although tissue resident immune have been demonstrated in several organs, composition human healthy islets scarcely studied. Here we aimed to investigate phenotype associated with non-diabetic organ donors. A flow cytometry analysis isolated from perfused pancreases (n = 38) was employed identify alpha, beta,...
Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of immune-mediated specific beta-cell loss. Since healthy pancreatic islets consist ~65% beta cells, this would lead to reduced islet size, while the number per pancreas volume (islet density) not be affected. In study, we compared density, and size distribution biopsies from subjects with recent-onset or long-standing T1D, that matched non-diabetic subjects. The results presented show preserved distribution,...
It has been proposed that unmethylated insulin promoter fragments in plasma derive exclusively from β cells, reflect their recent demise, and can be used to assess cell damage type 1 diabetes. Herein we describe an ultrasensitive assay for detection of a cell-specific DNA methylation signature, by simultaneous assessment 6 markers, identifies mixtures containing as little 0.03% (less than genome equivalent). Based on this assay, nondiabetic individuals (N = 218, aged 4-78 years) contained...
According to the consensus criteria developed for type 1 diabetes, an individual can be diagnosed with insulitis when ≥ 15 CD45+ cells are found within parenchyma or in islet–exocrine interface 3 islets. The aim of this study was determine frequency individuals 2 diabetes fulfilling these reference non-diabetic and diabetic individuals. Insulitis determined by examining pancreases 50, 13 44 organ donors no respectively. CD3+ (T cells) infiltrating islets were evaluated insulitic donors. In...
Summary In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within Nordic Network for Islet Transplantation. One thousand and thirty have been screened in Uppsala antibodies against glutamic acid decarboxylase (GADA) islet antigen-2 (IA-2A). The 32 that tested positive GADA (3·3% all donors) were studied more detail, together matched controls. Mean age among autoantibody-positive was 52·6 (range...
An early step in pancreas development is marked by the expression of transcription factor Pdx1 within pancreatic endoderm, where it required for specification all endocrine cell types. Subsequently, becomes restricted to β-cell lineage, plays a central role function. This pivotal at various stages makes an attractive target enhance differentiation and increase In this study, we used newly generated zebrafish reporter screen over 8000 small molecules modulators pdx1 expression. We found four...
Abstract Aims/hypothesis The Diabetes Virus Detection (DiViD) study is the first to laparoscopically collect pancreatic tissue and purified islets together with duodenal mucosa, serum, peripheral blood mononuclear cells (PBMCs) stools from six live adult patients (age 24–35 years) newly diagnosed type 1 diabetes. presence of enterovirus (EV) in these has previously been reported. Methods In present we used reverse transcription quantitative real-time PCR (RT-qPCR) sequencing characterise EV...
Abstract Aims The existence of insulin- or glucagon-expressing extra-islet endocrine cells scattered in the pancreas is well-known, but they have been sparsely characterized. aim this study was to examine their density, distribution, transcription-factor expression, and mitotic activity young non-diabetic subjects. Methods Multispectral imaging used PDX1, ARX, Ki67, insulin glucagon pancreatic tissue from organ donors aged 1–25 years. Results Extra-islet glucagon-positive were frequent all...
Present knowledge of innate immunity in infected cells relies on studies cell lines and animal models. In this study, primary human pancreatic islets Langerhans were used to study virus–host interactions a model the possible induction type 1 diabetes by enterovirus (EV). Human with strain EV isolated at onset diabetes, or exposed synthetic dsRNA (poly(I:C)), commonly mimic viral infection. Induction effect female sex hormone 17β-estradiol, known have cell-protective effects, islet chemokine...
To elucidate the etiology of type 1 diabetes, affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested involved in pathology disease and a reduction sympathetic islets was recently reported. In present study, we hypothesized that parasympathetic would altered diabetes pancreas. Human pancreatic specimens were obtained from unique cohort individuals with recent onset or long standing diabetes. Density axons assessed by immunofluorescence morphometry....
Insulin secretion is impaired with increasing age. In this study, we aimed to determine whether aging induces specific transcriptional changes in human islets. Laser capture microdissection was used extract pancreatic islet tissue from 37 deceased organ donors aged 1–81 years. The transcriptomes of the extracted islets were analysed using Ion AmpliSeq sequencing. 346 genes that co-vary significantly age found. There an increased transcription linked senescence, and several aspects cell cycle...
Type 1 diabetes is a chronic disease characterized by the selective destruction of insulin-producing cells in pancreas. Enterovirus (EV) prime candidate to initiate this and several inflammatory chemokines are induced EV infection. Nicotinamide has been shown protect isolated human islets, modulate chemokine expression. The aim study was evaluate effect nicotinamide on replication EV-induced secretion cytolysis islets. Two strains were used infect islets vitro, one lytic (Adrian) from child...
The cause of type 1 diabetes remains unknown. To dissect the link between hyperexpression human leukocyte antigen (HLA) class I on islet cells, we examined its expression in subjects with recent-onset diabetes. IHC showed seemingly pronounced diabetes, as well some nondiabetic subjects. In all subjects, HLA exocrine tissue was low. However, no difference level found and using Western blot, flow cytometry, real-time quantitative PCR, or RNA sequencing analyses. Also, messenger not increased...
Advanced ileocecal Crohn's disease (ICD) is characterized by strictures, inflammation in the enteric nervous system (myenteric plexitis), and a high frequency of NOD2 mutations. Recent findings implicate role another CD susceptibility gene, ATG16L1, host response against single-stranded RNA (ssRNA) viruses. However, viruses unknown. We hypothesized that human enterovirus species B (HEV-B), which are ssRNA with dual tropism both for intestinal epithelium system, could play ICD.We used...
The transcriptome of different dissociated pancreatic islet cells has been described in enzymatically isolated islets both health and disease. However, the isolation, culturing, dissociation procedures likely affect profiles, distorting biological conclusions. aim current study was to characterize Langerhans from subjects with without type 1 diabetes a way that reflects vivo situation highest possible extent. Islets were excised using laser capture microdissection directly frozen tissue...
In type 1 diabetes (T1D), most insulin-producing β cells are destroyed, but the trigger is unknown. One of possible triggers a virus infection and aim this study was to test if enterovirus affects glucose stimulated insulin secretion effect replication on cellular macromolecules organelles involved in secretion.Isolated human islets were infected with different strains coxsackievirus B (CVB) glucose-stimulated release (GSIS) measured dynamic perifusion system. Classical morphological...
The gut microbiota can play a role in pancreatitis and, likely, the development of type 1 diabetes (T1D). Anti-microbial peptides and secretory proteins are important mediators innate immune response against bacteria but their expression human pancreas is not fully known. In this study, immunohistochemistry was used to analyze seven anti-microbial (Defensin α1, α4, β1-4 Cathelicidin) two with known antimicrobial properties (REG3A GP2) pancreatic duodenal biopsies from 10 non-diabetic organ...
Abstract In experimental studies, pancreatic islet microvasculature is essential for endocrine function and mass, vascular morphology altered in diabetic subjects. Even so, almost no information available concerning human microvascular endothelial cell (MVEC) physiology gene expression. this study, islets exocrine tissue were acquired from organ donors with normoglycemia or impaired glucose metabolism (IGM) immediately after isolation. Following single-cell dissociation, primary islet- MVECs...