title: Endogenous hyperinsulinaemia in insulinoma patients is not associated with changes in beta-cell area and turnover in the tumor-adjacent pancreas.
abstract: BACKGROUND
  Insulin therapy has been suggested to preserve beta-cell mass in patients with diabetes through the mechanisms of beta-cell rest as well as direct effects on beta-cell proliferation. However, data about the effects of hyperinsulinism on beta-cell mass and turnover in humans are sparse.
  
  
  METHODS
  Pancreatic tissue specimens from five patients with pancreatic insulinomas and ten non-diabetic control subjects were examined. Pancreatic sections were stained for insulin, Ki67 (replication) and TUNEL (apoptosis), and quantitative morphometric analyses were performed.
  
  
  RESULTS
  Fractional beta-cell area was 1.11%±0.67% in the tumor-free pancreatic tissue of the insulinoma patients and 0.78%±0.26% in the control group (p=0.19). There also were no differences in islet size (p=0.62) or beta-cell nuclear diameter (p=0.20). Beta-cell replication and apoptosis were infrequently detected, without any measurable differences between the groups. There were also no differences in percentage of duct cells expressing insulin (p=0.47), a surrogate marker for islet neogenesis.
  
  
  CONCLUSIONS
  Beta-cell area and turnover are not significantly altered in the proximity of intra-pancreatic insulinomas. Future in vivo studies, ideally employing larger animal models, are warranted to further evaluate the impact of exogenous insulin on beta-cell turnover.
authors.affiliation: Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, Gudrunstrasse 56, Bochum, Germany.
authors.forename: Chiara
authors.initials: C
authors.lastname: Montemurro
authors.forename: Christina U
authors.initials: CU
authors.lastname: Köhler
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: Enzo
authors.initials: E
authors.lastname: Bonora
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism* / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007340:Insulinoma / Q000378:metabolism / Q000503:physiopathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen