title: Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes.
abstract: OBJECTIVE
  We investigated whether there was evidence of attempted beta cell regeneration in the pancreas obtained from a patient with recent-onset type 1 diabetes, and if so by what mechanism this occurred.
  
  
  METHODS
  We examined pancreas tissue from a lean 89-year-old patient (BMI 18.0 kg/m(2)) with recent-onset type 1 diabetes who had had a distal pancreatectomy to remove a low-grade pancreatic intraepithelial neoplasia.
  
  
  RESULTS
  In the tumour-free tissue, the fractional beta cell area was 0.54+/-0.2% of pancreas area (about one-third of that in non-diabetic humans). CD3-positive T lymphocytes and macrophages had infiltrated the majority of the islets. Subclassification of the T cell population revealed a predominance of CD8-positive cells over CD4-positive cells. Beta cell apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling [TUNEL] staining) was greatly increased, consistent with ongoing immune-mediated beta cell destruction. There was also a marked increase (more than approximately 100-fold) in the frequency of beta cell replication (0.69+/-0.15% Ki67-positive beta cells) in all blocks examined.
  
  
  CONCLUSIONS
  The present report provides direct evidence of attempted beta cell regeneration through the mechanism of beta cell replication in a case of newly diagnosed type 1 diabetes, and affirms that beta cell apoptosis is an important mechanism for beta cell loss in type 1 diabetes.
authors.affiliation: Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, University of California-Los Angeles, 900 Veteran Avenue, Los Angeles, CA 90095-7073, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Meier
authors.forename: J C
authors.initials: JC
authors.lastname: Lin
authors.forename: A E
authors.initials: AE
authors.lastname: Butler
authors.forename: R
authors.initials: R
authors.lastname: Galasso
authors.forename: D S
authors.initials: DS
authors.lastname: Martinez
authors.forename: P C
authors.initials: PC
authors.lastname: Butler
mesh_terms: D017668:Age of Onset; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000601:surgery; D012038:Regeneration