Pancreatic beta cell autophagy is impaired in type 1 diabetes

Conclusions/interpretation We provide evidence of islet macroautophagy/crinophagy impairment in human type 1 diabetes

Charanya Muralidharan; Abass M. Conteh; Michelle R. Marasco; Justin J. Crowder; Jeroen Kuipers; Pascal de Boer; Amelia K. Linnemann


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 proinsulinlysosome 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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