title: Omeprazole improves the anti-obesity and antidiabetic effects of exendin-4 in db/db mice (-4 db/db)*.
abstract: BACKGROUND
  In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes.
  
  
  METHODS
  The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.
  
  
  RESULTS
  Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.
  
  
  CONCLUSIONS
  Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.
authors: Department of Pharmacology & Toxicology, Zydus Research Centre, Cadila Healthcare Limited, Moraiya, Ahmedabad Anand Pharmacy College, Anand, Gujarat, India.
authors: Vishal
authors: V
authors: Patel
authors: Amit
authors: A
authors: Joharapurkar
authors: Tejal
authors: T
authors: Gandhi
authors: Kirti
authors: K
authors: Patel
authors: Nirav
authors: N
authors: Dhanesha
authors: Samadhan
authors: S
authors: Kshirsagar
authors: Vipin
authors: V
authors: Dhote
authors: Jaysukh
authors: J
authors: Detroja
authors: Rajesh
authors: R
authors: Bahekar
authors: Mukul
authors: M
authors: Jain
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D000077270:Exenatide; D005755:Gastrins / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy*; D009853:Omeprazole / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D019440:Anti-Obesity Agents; D005755:Gastrins; D007004:Hypoglycemic Agents; D020738:Leptin; D010455:Peptides; D014688:Venoms; D005934:Glucagon; D000077270:Exenatide; D009853:Omeprazole