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allergology (9)
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(Epi)genetic epidemiology (1)
(medical)genetics (5)
5jaars overleving (1)
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abdomen (1)
access to medicine (1)
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ACS-NSQIP surgical risk calculator (1)
activated clotting time (1)
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acute myocardial infarction (2)
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adverse side effects (1)
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ageing lungs (1)
Ageing, Nuclear Envelope, Nuclear Pore Complex (1)
aging (1)
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Allergy (1)
allogene stam cel transplantatie (2)
Allogeneic stem cell transplantation (1)
Alternative for epidural analgesia (1)
Amalgaam (2)
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ANCA associated vasculitis (1)
anesthesia (5)
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anesthesiology (2)
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Animal research (2)
ankylosing spondylitis (2)
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antibiotics (3)
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antidepressants (4)
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arterioveneuze fistel, dialyse shunt (1)
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autoimmune blistering diseases (1)
autoimmune disease (6)
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Autophagy (2)
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brain tumour (2)
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breast cancer (5)
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Calprotectin (2)
cancer (31)
cancer cell apoptosis (1)
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cancer patients (2)
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cardiac differentiation (1)
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cardiogenetics (2)
cardiology (10)
cardiometabolic health (1)
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Cardiovasculaire effecten (1)
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cardiovascular risk (1)
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care outside the guideliness (1)
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Catheterization lab (1)
celiac disease (4)
cell biology (1)
cell cycle (2)
cell death (3)
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Cervical spine (2)
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childbirth (1)
children (7)
ChIP assay (1)
cholangiocyte (1)
cholestasis (1)
cholesterol fluxes (1)
chromosomal abnormalities (1)
chromosome (1)
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chronic disease (2)
Chronic Kidney Disease (5)
chronic lung allograft dysfunction (1)
chronic ventilatory support (1)
Chronische pijn (2)
Circadian rhythmicity (1)
cirrhosis (2)
Clinical decision making (1)
clinical decision-making (1)
clinical diagnostics (4)
clinical epidemiology (1)
clinical genetics (1)
Clinical retrospective patient outcome study (1)
Clinical Severity Score (1)
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coagulation (1)
coating (1)
coccygodynie (1)
cochlear implant users (1)
cognition and outcome (2)
cognitive function (3)
cognitive impairment (1)
cognitive testing (1)
collect clinical information (1)
Colon carcinoma (1)
colonisation (1)
colorectal cancer (2)
colorectal cancer, CEA value, CT-scan, follow up (1)
colorectal surgery (3)
comorbidity: anxiety, aggression, emotion regulation problems, depression (1)
compensatory movements (1)
competency development (1)
complement (3)
complex congenital heart disease (1)
compliance (1)
complications (4)
Comprehensice geriatric assessment (1)
computed tomography (CT) (3)
Congenital anomalies (1)
congenital heart disease (3)
connective tissue disease (1)
Constipation (1)
continue glucose monitoring (1)
contraction (1)
contrastmiddel (1)
COPD (14)
Coronair angiografie (1)
coronary arteries (1)
coronary artery bypass grafting (1)
Coronary Artery Disease (3)
cosmetic outcome (1)
costs (3)
COVID-19 (6)
craniopharyngioma (2)
Craniotomy (1)
Crohn's disease (2)
Crohn's disease (3)
Crohn's disease (1)
CT (1)
CT imaging (2)
CT-scan (1)
cystic fibrosis (4)
cytokines (1)
Damage (1)
database (3)
database registry (1)
Deep brain stimulation (DBS) (4)
deletion (2)
delirium (1)
delivery agent (1)
dementia (3)
dental erosion (1)
dental hygiene (1)
dentist (1)
depression (4)
Depression, (2)
Depression, translational neuroscience (1)
dermatology (3)
development (3)
Developmental coordination disorder (1)
developmental disorder (1)
developmental disorders (1)
Developmental Dysplasia of the Hip (DDH) (1)
developmental psychopathology (1)
Dexamethasone (1)
diabetes (3)
Diabetes mellitus (4)
diabetis (1)
diagnostic importance (1)
diagnostic test (1)
diagnostics (3)
dialysis (3)
Diaphragm paralysis (1)
Diet (2)
dilated cardiomyopathy (1)
disease activity (1)
disease models (1)
Disease modifying therapy (1)
DNA (1)
DNA damage (1)
DNA damage response (1)
DNA methylation signatures (1)
donor (1)
Drosophila (2)
drug delivery (1)
Drug Interactions (1)
dry eye (2)
duplication (1)
Dupuytren's disease (1)
Dupuytren's disease (1)
Dystonia (4)
e-health (5)
early detection (1)
Early Onset Ataxia (2)
echo duplex, diagnotische waarde (1)
echocardiography (2)
echogenic bowel (1)
eco-anxiety (1)
Education (2)
EEG-EMG (1)
effects (1)
Ehealth (10)
Elder (1)
elderly (6)
elderly cancer patients (1)
elderly patients (2)
electroconvulsive therapy (1)
Electronic Nose (1)
EMG (1)
EMG-analysis (1)
emphysema (1)
EMSA (1)
enamel (1)
end-expiratory lung volume (1)
endocrine disrupting chemicals (1)
endocrine therapy (1)
endocrinology (1)
endometriosis (2)
Endophenotypes (1)
Endothelial Cell (2)
endothelial cells (1)
endoveneuze laser behandeling (1)
energy metabolism (3)
engineering (1)
enkelletsel (1)
eNose (1)
epidemiology (9)
epidermolysis bullosa (1)
epigenetics (4)
epithelial cells (1)
epithelial disorders (1)
ercp (1)
errors (1)
erythropoietin (1)
Esophageal cancer (1)
esophageal carcinoma (2)
Esophageal pressure (1)
esophagus surgery (2)
Essential tremor (3)
ESWL (2)
ethics (1)
evidence-based medicine (1)
EVLT (1)
Ex vivo lung perfussion (1)
exercise testing (1)
exercise therapy (1)
Exercise training (1)
Exergames (1)
exome sequencing (3)
Extreme prematuur (1)
Faecalibacterium prausnitzii (1)
familial hypercholesterolemia (1)
Family history (2)
Farmacologie (1)
farmacology (1)
fatigue (2)
fatty acids (1)
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FDG PET/CT (2)
fecal incontinence (1)
fertility (1)
fetal gender (1)
fibrosis (3)
filling (2)
First Episode Psychosis (2)
first trimester anomaly scan (1)
first trimester ultrasound (1)
fitness (1)
fluid administration, hemodynamic monitoring (1)
Fluorescence imaging (1)
fMRI (1)
fNIRS-monitoring (1)
foot ulcers (1)
frailty (2)
Frailty screening (2)
functional genetics (2)
Functional stroke mimic (1)
Fungal Infections (1)
fysiotherapie (1)
gait (1)
galectin-3 (1)
Galgangatresie (1)
game (1)
gangliosides (1)
GBA1-gene (1)
GECKO (1)
Gender (1)
gene enrichment (1)
gene expression (1)
gene regulation (1)
general medicine (1)
general movements (1)
general practice (3)
general practitioner (1)
genetic diseases (1)
Genetic sequencing (1)
genetic testing (1)
genetics (5)
genome analysis (1)
genomic instability (1)
genotype-phenotype correlation (1)
geriatric oncology (1)
geriatrics (2)
glaucoma (2)
Glioblastoma (1)
Gliomas (1)
global child health (1)
global health (2)
Glomerular filtration rate (1)
Glucocorticoids (1)
glucose homeostasis (1)
Group antenatal care (1)
growth hormone deficiency (1)
Guidelines (2)
Gunanine Nucleotide Exchange Factor (1)
Gut Microbiota Composition (2)
gut-liver acis (1)
gyneacological oncology (1)
gynecological oncology surgery (1)
haemophilia (2)
hand (1)
Head and neck cancer (5)
Health care professionals (1)
Health care utilization (1)
health economics (3)
Health indicators (1)
Health literacy (1)
health-related quality of life (4)
healthcare education (1)
hearing impairment (1)
hearing rehabilitation (1)
heart (14)
heart failure (7)
heart transplantation (1)
heart valve replacement (1)
heat shock proteins (1)
Heel prick Screening (1)
hematology, cancer, critical care, outcome (3)
hematopoiesis (5)
hemodynamic monitoring (2)
hemodynamics (1)
hemostasis (2)
heparin induced thrombocytopenia (1)
hepatitis (2)
hepatocellular carcinoma (1)
hereditary cancer (1)
hereditary kidney disease (1)
hereditary tumours (1)
herniated discs (1)
HFOV (2)
Hibernation (4)
Hidradenitis suppurativa (1)
hip (1)
hip and knee prothesis (2)
Hip artroplasty (1)
Historical controls (1)
HIV (3)
Hodgkin lymphoma (2)
Home mechanical ventilation (3)
Honours education (1)
hormone receptors (1)
HPB surgery (1)
huisarts (1)
Huisartsgeneeskunde (1)
human genetics (1)
human hematopoietic stem cells (3)
Humeral Fractures (1)
hydrochlorothiazide (1)
hydrogen sulfide (1)
hymenoptera venom allergy (1)
hyperglycaemia (1)
Hyperkinetic movement disorders (2)
Hypertensie (1)
hypoglycemia (1)
hypophospatemic rickets (1)
hypoplastic left heart syndrome (1)
hypotension (1)
IBD (4)
IGF-1 (1)
image biomarker (2)
imaging (10)
imaging, biomarkers (1)
Immune checkpoint inhibitors (3)
immune response (1)
immune suppression (1)
Immune-related adverse events (1)
immunity (1)
immunology (11)
immunosuppression (1)
immunotherapy (4)
implant infection (2)
in vitro (1)
in vitro fertilization (1)
Inborn Error of Metabolism (1)
incidence (1)
incontinence (2)
individualised treatment (1)
infant (2)
infant assessment (2)
infant development (3)
Infant Stool Colour Card (1)
infection (3)
Infectious diseases (1)
Infective Endocarditis (1)
inflammation (5)
Inflammatory bowel disease (3)
Inflammatory rheumatic disease (3)
Informatie-uitwisseling (1)
Information technology (1)
Inguinal Hernia Surgery (1)
innovatie van zorg (2)
insulin (1)
insuline-glucose metabolism (1)
insulitis (1)
Integrative care (1)
intellectual disability (1)
interactie (1)
interprofessional education (2)
interventions in obstetrics (1)
Interviews (1)
Interviewstudie (1)
intestinal disease (2)
intestinal disorder (1)
intestinal integrity (1)
intestinal transplantation (2)
Intestinal wall permeability (1)
intestine (1)
Intracraniele druk (1)
Intraoperative neurophysiology (1)
IONM (1)
iPSC (1)
iron deficiency (2)
ischemia (3)
ischemia-reperfusion injury (1)
ischemia/reperfusion injury (2)
ischemic stroke (2)
Isolation (1)
isotopes (1)
IVF (3)
jaundice (2)
joint (2)
Ki67 proliferation index (1)
kidney (6)
kidney disease (5)
Kidney Donation (3)
kidney transplantation (13)
kidneydonor (1)
kinetic modeling (1)
Klinische onderzoeksstage (1)
knockout mouse (1)
kwaliteit van leven (2)
kwaliteit van zorg (1)
laboratory animals (10)
language development (1)
language screening (1)
laparoscopy (1)
laryngectomy (3)
late effects of treatment (1)
Leadership (1)
learning curve sonologist (1)
leefstijl (1)
leukemia (3)
leukemic stem cells (2)
LifeLines (2)
lifestyle (3)
liposomes (1)
lipotoxicity (1)
liver (3)
liver cancer (1)
liver disease (5)
liver diseases (1)
liver failure (1)
liver fibrosis (1)
liver metastases (1)
liver resection (1)
liver transplantation (9)
livercirrhosis (1)
locally advanced rectal caner (1)
locomotion (1)
long-term survival (1)
lumg transplantation (1)
lung (4)
lung cancer (5)
Lung function (1)
lung mechanics (2)
lung nodules (2)
lung recruitment (1)
lung transplantation (4)
lymphoma (2)
lynch syndrome (1)
machine learning (Matlab/Rstudio) (1)
machine perfusion (2)
major depressive disorder (1)
mass spectrometry (2)
mast cells (1)
mastocytosis (3)
measurement tool (1)
mechanical ventilation (9)
medical comorbidity (1)
medical device (4)
medical education (3)
medical imaging (8)
medically unexplained symptoms (2)
medication (3)
Medication reviews (1)
medication safety (1)
medication treatment (1)
medicine (1)
melanoma (5)
Meningioma (1)
meno-pauze (1)
mental retardation (1)
metabolic diseases (5)
Metabolic signaling (1)
metabolic syndrome (3)
metabolism (3)
metabool syndroom (3)
metformin (1)
method development (2)
microbiome (1)
microbiota (3)
microcephaly (1)
Microglia (1)
microRNA (2)
Minimally invasive parathyroidectomy (1)
mitochondria (1)
MitraClip (1)
Mobile electrocardiogram devices (1)
Mobility (1)
Modus partus (1)
molecular biology (2)
molecular chaperones (1)
Molecular Fluorescence Guided Surgery (1)
molecular mechanisms (1)
molecular microbiology (1)
Molecular tumour board (1)
molecular typing (1)
Monoclonal antibodies (1)
monocytes (1)
mood disorders (1)
Motor development (2)
Mouse models (1)
movement disorders (3)
MRI (7)
MRI / CT (1)
MRI / magnetic resonance imaging (3)
MRI brain (1)
MRS (1)
mucus clearance (1)
multi-morbidity (1)
Multi-organ failure (1)
Multi-phase CT (1)
multidrug resistance (1)
Multimorbidity (3)
multiple myeloma (2)
multiple sclerosis (3)
Musculoskeletal pain (1)
Music (1)
music intervention (1)
mutations (2)
myelin (1)
myocardial infarction (2)
myoclonus (1)
myoclonus dystonia (1)
NASH (1)
nasopharyngeal carcinoma (1)
Necrotische Enterocolitis (1)
necrotising enterocolitis (1)
nefropathie (1)
neglected diseases (1)
Neglected Tropical Diseases (1)
neoadjuvant chemoradiotherapy (1)
Neonatal growth (1)
neonatal hypoglycemia (1)
Neonatal hypoxic-ischaemic encephalopathy (1)
Neonatal outcome (1)
neonates (2)
neonatology (1)
nephrology (2)
neuro-endocrine tumors (1)
neurobiology (1)
neurocognition (1)
neurodegeneration (4)
neurodegenerative diseases (3)
neurodevelopmental impairment (1)
neurodevelopmental outcome (1)
neuroendocrine tumor (1)
Neuroimaging (3)
neuroinflammation (1)
neurological development (1)
neurology (1)
neuromuscular blockade (1)
neuropathic pain (1)
neuropathy (1)
neuropsychiatric symptoms (1)
Neurosurgery (1)
neurotransmitters (1)
neutropenia (1)
new genes (1)
nier (1)
non-Hodgkin's disease (1)
Non-invasive ventilation (2)
Non-motor symptoms (2)
Noordzeeziekte (1)
nuclear receptors (1)
nursing home (1)
Nursing home residentss (1)
nutrient addiction (1)
nutrition (8)
obesity (6)
Occupational exposures (1)
Occupational health (1)
Older adults (1)
oligodendrocytes (1)
oncological epidemiology (2)
oncology (5)
oncoplastic surgery (1)
ongeplande heropname (1)
online wearables (1)
operative surgical procedure (1)
opthalmologic problems (1)
organ preservation (3)
organ transplant (1)
organ transplantation (2)
orthopedics (3)
osteomyelitis (1)
otolaryngology (1)
Ouderen (1)
outcome (1)
outcome and cognition (1)
Outcome Assessment (1)
Outcome measurement (5)
Outcomes (2)
ovarian cancer (3)
Overactieve blaas (2)
overweight (2)
Overweight/obesity (1)
oxidative stress (2)
oxygenation (1)
pain (2)
PALB2 mutation (1)
palliatief (1)
Palliatieve zorg (3)
palliative care (1)
pancreatic resection (1)
pancreatoduodenectomie (1)
parental support (1)
Parkinson disease (4)
Parkinson's disease (4)
Parkinson's disease (2)
Parkinson’s disease (1)
Parkinson's disease (4)
Participation restriction (1)
pathological complete response (1)
pathology (1)
pathway analysis (1)
Patiënt-gerichtheid (1)
patient centered care (1)
patient experiences (2)
Patient perspective (1)
patient related research (1)
patient satisfaction (1)
Patient-Reported-Outcomes (1)
PD-L1 immunohistochemistry (1)
pediatric cardiology (2)
Pediatric gastroenterology (1)
Pediatric rehabilitation (1)
pediatrics (6)
Percutane Nefro-Litholapaxy (2)
Percutaneous coronary intervention (PCI) (1)
Percutaneous intervention (2)
Peri-Acetabular Osteotomy (PAO) or Bernese/Ganz osteotomy (1)
perinatal care and psychiatry (1)
perineal wound healing (1)
periodontitis (1)
perioperative care (1)
Periprosthetic joint infection (1)
peritonitis (1)
Persistent somatic symptoms (1)
personal medicine (1)
personalized (1)
Personalized medicine (3)
PET (4)
pet scintigraphy (1)
PET-tracer (1)
Peyronie disease (1)
pharmacodynamics (1)
pharmacokinetics (1)
pharmacology (4)
Phelan-McDermid syndrome (1)
phenomenology (1)
phenotype-genotype study (1)
phenylketonuria (1)
photometry (1)
physical activity (3)
physical and mental functioning (1)
physical therapy (1)
physiology (2)
placenta (1)
plasmacytoma (1)
plastic surgery (1)
platelet (1)
polisomnography (1)
Polycomb (1)
polypharmacy (6)
population screening (2)
portal hypertension (1)
Positron Emission Tomography (1)
Postgraduate Medical Education (2)
postoperative complications (2)
postoperative outcome (1)
postoperative pain (1)
posttraumatic (1)
postural control (1)
potassium (1)
pre-clinical imaging (1)
pre-peritoneal wound catheters (1)
Precision medicine (1)
predictiemodel (1)
Predictiemodellen (1)
prediction (1)
prediction modeling (2)
preeclampsia (1)
pregnancy (11)
Prematuren (1)
prenatal diagnosis (2)
prenatal diagnostics (2)
prenatal programming (1)
preservation fluids (1)
preterm (1)
preterm birth (1)
Prevalence of cancer (1)
prevention (4)
preventive cardiovascular medication (1)
primairy health care (1)
primary care (7)
primary care, gastro-enteritis, children, out-of-hours service, pediatrics. (2)
Primary Hyperparathyroidism (1)
probiotics (1)
Proefschrift (1)
prognosis (2)
Prolapse surgery (1)
proliferation (1)
Promoveren (1)
prospective cohort study (1)
prostate cancer (1)
Prosthetic Valve (1)
protein aggregation (1)
protein kinase inhibitors (1)
protein restoration therapy (1)
proteomics (3)
prothrombin complex concentrate (1)
PSMA PET/CT (1)
Psychiatric symptoms (1)
psychiatry (1)
psychiatry, high-field MRI (1)
Psychology (1)
psychosis (1)
psychosocial (2)
psychosocial and lifestyle determinants (1)
psychotherapy (1)
Publiceren (1)
pulmonary embolism (1)
pulmonary hypertension (1)
pulmonary rehabilitaion (1)
Pulmonary rehabilitation (1)
QST (1)
qualitative research (4)
quality of life (7)
quality of reduction (1)
Quantification (1)
quantitative sensory testing (1)
questionnaire (3)
questionnaire research (1)
Radiology (11)
radiotherapy (31)
Randomized comparative trial (1)
randomized controlled trial (1)
raynaud (1)
RCT (1)
real world dosing (1)
Recommendation (1)
recovery (1)
rectal cancer (2)
rectum carcinoma (1)
referral (1)
Refugee women (1)
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Type 1 diabetes-induced alterations in islets of Langerhans
Keywords: Advanced Microscopy
beta cell destruction
insulitis
Researchers:
dr. B.N.G. Giepmans
P. de Boer
Nature of the research:
Cell Biology/ Medical Biology: - Electron microscopy sample preparation, including ultramicrotomy
- Post/pre-embedding immunolabeling
- (Confocal) light microscopy
- Large-scale electron microscopy5, 7 (www.nanotomy.org)
Fields of study:
cell biology
molecular imaging
diabetes
Background / introduction
Type 1 diabetes (T1D) is associated with loss of insulin producing beta-cells in the pancreatic islets of Langerhans resulting in impaired glucose uptake of target cells and consequently hyperglycaemia. In some rodent models beta-cell reconstitution from other cell types, called transdifferentiation, is observed either spontaneous or induced1-3. A hallmark of transdifferentiation is the presence of by bihormonal cells. Spontaneous transdifferentiation was only observed in selective near-total cell loss in transgenic mouse model of diphtheria toxin-induced selective beta-cell ablation1. However, using large-scale correlative light and electron microscopy (CLEM)4, 5 we found bihormonal cells in normoglycaemic rats. Furthermore, hormone granules were observed in aberrant exocrine cells and recently effects on the exocrine pancreas in T1D patients was reported6. This raises the intriguing possibility to examine whether transdifferentiation, via endocrine and/or exocrine cells, play a role in early-onset T1D for example to counteract an increased demand of insulin.
Research question / problem definition
Investigate the role of bihormonal cells and/or affected exocrine pancreas in normoglycaemic, diabetic-prone rats and human material in relation to early-onset T1D.
Workplan
Immunolabeling to identify different cell types (incl. bihormonal) in islets of Langerhans of both rat and human material in a CLEM approach.
Quantum dots are used for immune-fluorescence and EM localization7
Analyse large-scale electron microscopy datasets to score the appearance of bihormonal cells, aberrant exocrine cells and/or other abnormalities in both rat and human T1D material versus controls.
References
1. Thorel, F. et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature 464, 1149-1154 (2010).
2. Chera, S. et al. Diabetes recovery by age-dependent conversion of pancreatic delta-cells into insulin producers. Nature 514, 503-507 (2014).
3. Piran, R. et al. Pharmacological induction of pancreatic islet cell transdifferentiation: relevance to type I diabetes. Cell. Death Dis. 5, e1357 (2014).
4. de Boer, P., Hoogenboom, J.. & Giepmans, B. N. Correlated light and electron microscopy: ultrastructure lights up! Nat. Methods 12, 503-513 (2015).
5. Ravelli, R.. et al. Destruction of tissue, cells and organelles in type 1 diabetic rats presented at macromolecular resolution. Sci. Rep. 3, 1804 (2013).
6. Campbell-Thompson, M. L. et al. The influence of type 1 diabetes on pancreatic weight. Diabetologia 59, 217-221 (2016).
7. Kuipers, J., de Boer, P. & Giepmans, B. N. Scanning EM of non-heavy metal stained biosamples: Large-field of view, high contrast and highly efficient immunolabeling. Exp. Cell Res. 337, 202-207 (2015).