Conclusions/interpretation We provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes
2021
Key concepts
- Cathepsin H
- chloroquine
- apoptosis
- Autoimmune disease
- homeostasis
- insulin
- Autophagy
- Type 1 diabetes
- autophagosome
- light chain
- reactive oxygen species
- proinsulin
- macroautophagy
- Electron microscopy
- pathogenesis
- lysosomes
- pancreatic beta cell
- diabetes
- Regions of interest
- LC3–
- Network for Pancreatic Organ Donors with Diabetes
- lysosomal-associated membrane protein 1
Scholarcy highlights
- Beta cell reactive oxygen species accumulation is implicated as a triggering event during the development of type 1 diabetes
- Evidence of impaired autophagy in diabetic non-obese diabetic mice To determine if autophagy is impaired in a mouse model of spontaneous autoimmune diabetes, we analysed pancreases from diabetic NOD mice, comparing them with both non-diabetic NOD mice and non-obese diabetes-resistant mice, which do not develop insulitis or diabetes and are MHC-matched to NOD mice
- We reasoned that if autophagy is impaired in the context of spontaneous autoimmune diabetes, this would be evident through altered colocalisation of LC3 with lysosomal-associated membrane protein 1
- We observed a significant reduction in the LC3–LAMP1 colocalisation in diabetic NOD mouse islets when compared with either NOR or non-diabetic NOD mouse islets
- There was no significant difference in the colocalisation of LC3 with LAMP1 when comparing NOR with non-diabetic NOD mouse islets
- We observed a significant increase in proinsulin but a reduction in proinsulin–lysosome colocalisation in beta cells of donors with type 1 diabetes when compared with beta cells of both non-diabetic and autoantibody-positive donors
- These results have potential clinical implications for type 1 diabetes prevention and we anticipate that further studies of autophagy and crinophagy in the context of type 1 diabetes will yield additional insight for therapeutic targets in the future
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