ORIGINAL: Understanding basic human beta cell physiology is crucial to targeted therapies and prevention strategies for type 1 diabetes. Clinical signs in type 1 diabetes start when beta cell function and/or numbers are unable to maintain adequate blood glucose levels. After onset of type 1 diabetes, life-long insulin replacement therapy is needed. Factors regulating human beta cell regeneration are poorly understood. The purpose of these studies are to: 1) define pancreatic beta and alpha cell populations and how diabetes alters their function and numbers, 2) characterize potential autoimmune mediators of islet inflammation (insulitis) and resultant beta cell death, and 3) correlate lymphocytic populations in pancreatic and nonpancreatic lymph nodes and spleen between pre-diabetes and type 1 diabetic patients.

ADDENDUM: The goal of this addendum is to utilize large scale 3D human pancreas imaging methods for quantification of islet neuroendocrine cells and intra-pancreatic neurons and fibers. The autonomic neuro-insular network may be an unrecognized co-factor in the loss of functional beta cells during the progression to type 1 diabetes and following an islet transplantation. This proposal is expected to provide key data regarding neuronal pathways regulating beta cell regeneration.