title: Impact of proton pump inhibitor treatment on pancreatic beta-cell area and beta-cell proliferation in humans.
abstract: BACKGROUND
  Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans.
  
  
  METHODS
  Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined. The group was subdivided into patients without diabetes (n = 27), pre-diabetic patients (n = 31) and patients with diabetes (n = 35).
  
  
  RESULTS
  Fasting glucose and HbA1c levels were not different between patients with and without PPI therapy (P = 0.34 and P = 0.30 respectively). Beta-cell area was higher in patients without diabetes than in patients with pre-diabetes or diabetes (1.33 ± 0.12%, 1.05 ± 0.09% and 0.66 ± 0.07% respectively; P < 0.0001). There was no difference in beta-cell area between patients with and without PPI treatment (1.05 ± 0.08% vs 0.87 ± 0.08%, respectively; P = 0.16). Beta-cell replication was rare and not different between patients with and without PPI therapy (P = 0.20). PPI treatment was not associated with increased duct-cell replication (P = 0.18), insulin expression in ducts (P = 0.28) or beta-cell size (P = 0.63).
  
  
  CONCLUSIONS
  These results suggest that in adult humans, chronic PPI treatment does not enhance beta-cell mass or beta-cell function to a relevant extent.
authors: Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Thomas G K
authors: TG
authors: Breuer
authors: Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Laura
authors: L
authors: Borker
authors: Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Daniel R
authors: DR
authors: Quast
authors: Institute for PathologyRuhr-University Bochum, Bochum, Germany.
authors: Andrea
authors: A
authors: Tannapfel
authors: Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Wolfgang E
authors: WE
authors: Schmidt
authors: Department of SurgerySt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors: Waldemar
authors: W
authors: Uhl
authors: Diabetes DivisionSt. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany juris.meier@rub.de.
authors: Juris J
authors: JJ
authors: Meier
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011236:Prediabetic State / Q000188:drug therapy / Q000378:metabolism*; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D054328:Proton Pump Inhibitors