title: Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas.
abstract: OBJECTIVE
  Exendin-4 is a 39 amino acid agonist of the glucagon-like peptide receptor and has been approved for treatment of type 2 diabetes. Many reports describe an increased incidence of acute pancreatitis in humans treated with exendin-4 (exenatide). Previous studies have evaluated the effect of exendin-4 on beta cells and beta cell function. We evaluated the histological and biochemical effects of exendin-4 on the pancreas in rats.
  
  
  METHODS
  We studied 20 Sprague-Dawley male rats, ten of which were treated with exendin-4 and ten of which were used as controls. The study period was 75 days. Serum and pancreatic tissue were removed for biochemical and histological study. Blood glucose, amylase, lipase, insulin and adipocytokines were compared between the two groups.
  
  
  RESULTS
  Animals treated with exendin-4 had more pancreatic acinar inflammation, more pyknotic nuclei and weighed significantly less than control rats. They also had higher serum lipase than control animals. Exendin-4 treatment was associated with lower insulin and leptin levels as well as lower HOMA values than in the untreated control group.
  
  
  CONCLUSIONS
  Although the use of exendin-4 in rats is associated with decreased weight gain, lower insulin resistance and lower leptin levels than in control animals, extended use of exendin-4 in rats leads to pancreatic acinar inflammation and pyknosis. This raises important concerns about the likelihood of inducing acute pancreatitis in humans receiving incretin mimetic therapy.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Missouri Kansas City, Kansas City, MO 64108, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Nachnani
authors.forename: D G
authors.initials: DG
authors.lastname: Bulchandani
authors.forename: A
authors.initials: A
authors.lastname: Nookala
authors.forename: B
authors.initials: B
authors.lastname: Herndon
authors.forename: A
authors.initials: A
authors.lastname: Molteni
authors.forename: P
authors.initials: P
authors.lastname: Pandya
authors.forename: R
authors.initials: R
authors.lastname: Taylor
authors.forename: T
authors.initials: T
authors.lastname: Quinn
authors.forename: L
authors.initials: L
authors.lastname: Weide
authors.forename: L M
authors.initials: LM
authors.lastname: Alba
mesh_terms: D054392:Adipokines / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000681:Amylases / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008049:Lipase / Q000097:blood / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000494:pharmacology*
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008049:Lipase; D000681:Amylases