A5044746874- Diabetes and associated disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Celiac Disease Research and Management
- Immune Cell Function and Interaction
- Digestive system and related health
- Diet, Metabolism, and Disease
- Gut microbiota and health
- Glycosylation and Glycoproteins Research
- Gestational Diabetes Research and Management
- Microscopic Colitis
- Ion channel regulation and function
- Birth, Development, and Health
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Adipose Tissue and Metabolism
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pancreatitis Pathology and Treatment
- Calcium signaling and nucleotide metabolism
- Liver Disease Diagnosis and Treatment
- Diabetes Treatment and Management
- Sphingolipid Metabolism and Signaling
Rigshospitalet
2016-2025
Copenhagen University Hospital
1984-2022
Moesgaard Museum
2009-2021
BioInnovation Institute
2014-2016
University of Copenhagen
1987-2011
Kommunedata (Denmark)
1978-2003
University of Naples Federico II
2003
University of Campania "Luigi Vanvitelli"
2003
Czech Academy of Sciences, Institute of Microbiology
2002
Inserm
1999
γ-Aminobutyric acid (GABA) has been proposed to function as a paracrine signaling molecule in islets of Langerhans. We have shown that rat β-cells release GABA by Ca2+-dependent exocytosis synaptic-like microvesicles. Here we demonstrate thus released can diffuse over sufficient distances within the islet interstitium activate GABAA receptors neighboring cells. Confocal immunocytochemistry revealed presence glucagon-secreting α-cells but not β- and δ-cells. RT-PCR analysis detected...
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, effects reducing gluten-rich food items including wheat, barley and rye cereals healthy adults are unclear. Here, we undertook randomised, controlled, cross-over trial involving 60 middle-aged Danish without known disorders with two 8-week interventions comparing (2 g gluten per day) high-gluten (18 day), separated by washout period at least six weeks habitual (12 day). We find that,...
We have monitored electrical activity, voltage-gated Ca2+ currents, and exocytosis in single rat glucagon-secreting pancreatic A-cells. The A-cells were electrically excitable generated spontaneous Na+- Ca2+-dependent action potentials. Under basal conditions, was tightly linked to influx through ω-conotoxin-GVIA–sensitive (N-type) channels. Stimulation of the with adrenaline (via β-adrenergic receptors) or forskolin produced a greater than fourfold PKA-dependent potentiation...
It is important for our understanding of the pancreatic islets to study whether new are able form in intact pancreas. We developed a method determine total number and mean volume islets, we used this expansion islet mass ob/ob mice (n = 8), using ob/+ 8) as controls. The was increased by factor 3.6 compared with mice, whereas, importantly, did not differ among (3,193 ± 160 vs. 3,184 142 P 0.97). coefficient variation distribution equal two groups, showing that existing expand their same...
Background Epidemiological as well animal studies have shown that environmental factors such nutrition contribute to the development of diabetes. In this study we investigated whether early introduction a gluten-free diet can influence onset and/or incidence diabetes, insulitis and number gut mucosal lymphocytes, in non-obese diabetic (NOD) mice. Methods Gluten-free standard Altromin diets (with same milk protein vitamin content) were given breeding pairs NOD mice first generation female...
In isolated rat pancreatic alpha-cells, glucose, arginine, and the sulfonylurea tolbutamide stimulated glucagon release. The effect of glucose was abolished by KATP-channel opener diazoxide as well mannoheptulose azide, inhibitors glycolysis mitochondrial metabolism. Glucose inhibited activity 30% (P<0.05; n=5) doubled free cytoplasmic Ca2+ concentration. cell-attached recordings, azide opened KATP channels. N-type Ca2+-channel blocker omega-conotoxin Na+-channel tetrodotoxin glucose-induced...
Glucagon, secreted by the pancreatic alpha-cells, stimulates insulin secretion from neighboring beta-cells cAMP- and protein kinase A (PKA)-dependent mechanisms, but it is not known whether glucagon also modulates its own secretion. We have addressed this issue combining recordings of membrane capacitance (to monitor exocytosis) in individual alpha-cells with biochemical assays cAMP content intact islets, as well analyses receptor expression pure alpha-cell fractions RT-PCR. Glucagon...
OBJECTIVE The aim if the study was to investigate whether children born older mothers have an increased risk of type 1 diabetes by performing a pooled analysis previous studies using individual patient data adjust for recognized confounders. RESEARCH DESIGN AND METHODS Relevant published before June 2009 were identified from MEDLINE, Web Science, and EMBASE. Authors contacted asked provide or conduct prespecified analyses. Risk estimates maternal age calculated each study, after adjustment...
Early-life interventions in the intestinal environment have previously been shown to influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet, known decrease incidence of type 1 diabetes, would protect against development when fed only during pregnancy and lactation period. Pregnant nonobese diabetic (NOD) mice were GF or standard diet until all pups weaned diet. The early-life dramatically decreased insulitis. Gut microbiota analysis by 16S rRNA gene sequencing...
Abstract Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also the immune system. This further suggested to link Cesarean section (C-section) an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section cross-fostering a genetically distinct strain influence key markers mice. Gut profiling by denaturing gradient gel electrophoresis 454/FLX-based 16S rRNA gene...
Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion controlling apoptosis, as studied animal models cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes increasing levels sulfatide would prevent NOD mice. We examined amount distribution pancreatic islets immunohistochemistry, immunofluorescence electron microscopy. Transcriptional analysis was used evaluate...
Abstract Objective To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. Design National prospective cohort study. Setting health information registries Denmark. Participants Pregnant Danish women enrolled into Birth Cohort, January 1996 October 2002, Main outcome measures Maternal intake, based on maternal consumption containing foods, was reported a 360 item food frequency questionnaire at week 25 pregnancy. Information occurrence...
1 Measurements of cell capacitance were used to investigate the molecular mechanisms by which somatostatin inhibits Ca2+-induced exocytosis in single rat glucagon-secreting pancreatic α-cells. 2 Somatostatin decreased exocytotic responses elicited voltage-clamp depolarisations 80 % presence cyclic AMP-elevating agents such as isoprenaline and forskolin. Inhibition was time dependent half-maximal within 22 s. 3 The inhibitory action concentration with an IC50 68 nm prevented pretreatment...
High-resolution capacitance measurements were used to explore the effects of gut hormones GLP-I(7-36) amide [glucagon-like peptide I(7-36) amide] and GIP (glucose-dependent insulinotropic polypeptide) on Ca2+-dependent exocytosis in glucagon-secreting rat pancreatic alpha-cells. Both peptides produced a greater than threefold potentiation secretion evoked by voltage-clamp depolarizations, an effect that was associated with approximately 35% increase Ca2+ current. The stimulatory actions...
The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. two forms of (GAD64 and GAD67) are encoded by different genes both rats humans. By situ hybridization analysis rat human pancreases, expression was detected islets, whereas only GAD64 mRNA islets. Immunocytochemical pancreatic sections or isolated islets with antibodies to GAD67 combination insulin, glucagon, SRIF confirmed that were β-cell specific In contrast, was, addition β-cells, also surprisingly...