(#9) Evidence of increased telolysosomes presence in alpha and beta cells of autoantibody positive human organ donors

PRESENTED BY: Charanya Muralidharan

Authors
First NameLast NameAffiliation/Institution
CharanyaMuralidharanIndiana University School of Medicine
AmeliaLinnemannIndiana University School of Medicine
 

Purpose

Autophagic degradation is a dynamic recycling process that contributes to cellular homeostasis and mitigation of cellular stress. While there are multiple forms of -phagic degradation processes, a common endpoint is the final degradation step in the lumen of the acidic lysosomes. Post-mitotic cells, including beta cells, can accumulate tertiary lysosomes called telolysosomes which contain oxidized proteins and lipids that are undigestible. We recently found that autophagy is impaired in the beta cells of individuals with T1D and also in islets of diabetic NOD mice. We also observed a significant increase in the number of telolysosomes in the beta cells of autoantibody positive individuals. We have now extended our analyses to the alpha cells of autoantibody positive organ donors.
 

Methods

We used the electron microscopic images of nPOD pancreas tissue sections, available from www.nanotomy.org/OA/nPOD. Telolysosomes in the alpha cells were identified and quantified in tissue sections from nondiabetic and autoantibody positive organ donors.
 

Summary of Results

By implementing immunofluorescence analysis and electron microscopy, we previously observed an increase in the number of autophagosomes (p=0.0458) and telolysosomes (p=0.0024) in the beta cells of autoantibody positive organ donors when compared to nondiabetic organ donors. Currently, by taking advantage of electron microscopic images from the nanotomy repository, we also report a significant increase in telolysosomes (p=0.03) in the alpha cells of autoantibody positive individuals when compared to alpha cells of nondiabetic organ donors.
 

Conclusions

We now report our observation of an increased number of telolysosomes in the alpha cells of autoantibody positive individuals, suggesting an accumulation of lysosomes with highly oxidized proteins and lipids in both alpha and beta cells of autoantibody positive individuals. This observation in conjunction with our previous observation of increased autophagosomes in beta cells of autoantibody positive donors suggest a possible defect in the lysosomes in the islet cells during disease pathogenesis, prior to the development of hyperglycemia. Further studies will be required to confirm these observations and address when lysosomes become defective during the pathogenesis of type 1 diabetes.