Oxidative stress occurs when increased production of cellular oxidants (e.g. Reactive Oxygen Species, or ROS) is not compensated  for  by  an  increase  in  cellular  antioxidants/antioxidant  enzymes.   A  considerable body  of  evidence  supports  the  conclusion  that  oxidative  stress  is  a common  feature  of type  1 diabetes (T1D), and that the process of autophagy plays a key role in mitigation of ROS to reduce oxidative stress and promote -cell survival. Indeed, we recently found that coupling of autophagy to the antioxidant response could reduce-cell ROS, and protect against oxidative damage and apoptosis in an STZ model of diabetes in mice. Autophagy has long been known to play a critical role in -cell homeostasis and survival in the context of type 2 diabetes, however much less is known about the role that autophagy plays in the pathogenesis of type 1 diabetes, particularly in humans. Therefore,  in  this  project  we  propose  to  analyze autophagy in  islets  from  cadaveric donors with type 1 diabetes. Number, spatial organization of autophagosomes and lysosomes, and  colocalization  of  these  vesicles  will  be  quantified.  Further,  since  a  specialized  form  of autophagy  known  as  crinophagy  is  important  for insulin  homeostasis,  we  will also determine  if lysosome changes are associated with the changes in proinsulin that have been recently reported in islets from type 1 diabetic individuals.