title: Omeprazole and PGC-formulated heparin binding epidermal growth factor normalizes fasting blood glucose and suppresses insulitis in multiple low dose streptozotocin diabetes model.
abstract: OBJECTIVE
  Our objective was to develop novel nanocarriers (protected graft copolymer, PGC) that improve the stability of heparin binding EGF (HBEGF) and gastrin and then to use PGC-formulated HBEGF (PGC-HBEGF) and Omeprazole (+/- PGC-gastrin) for normalizing fasting blood glucose (FBG) and improving islet function in diabetic mice.
  
  
  METHODS
  HBEGF, PGC-HBEGF, Omeprazole, Omeprazole + PGC-HBEGF, Omeprazole + PGC-gastrin + PGC-HBEGF and epidermal growth factor (EGF) + gastrin were tested in multiple low dose streptozotocin diabetic mice.
  
  
  RESULTS
  Omeprazole + PGC-HBEGF normalized FBG and is better than EGF + gastrin at improving islet function and decreasing insulitis. Groups treated with Omeprazole, Omeprazole + PGC-HBEGF, or EGF + gastrin have significantly improved islet function versus saline control. All animals that received PGC-HBEGF had significantly reduced islet insulitis versus saline control. Non-FBG was lower for Omeprazole + PGC-gastrin + PGC-HBEGF but Omeprazole + PGC-HBEGF alone showed better FBG and glucose tolerance.
  
  
  CONCLUSIONS
  Omeprazole + PGC-HBEGF provides a sustained exposure to both EGFRA and gastrin, improves islet function, and decreases insulitis in multiple low dose streptozotocin diabetic mice. Although HBEGF or EGF elevates non-FBG, it facilitates a reduction of insulitis and, in the presence of Omeprazole, provides normalization of FBG at the end of treatment. The study demonstrates Omeprazole and PGC-HBEGF is a viable treatment for diabetes.
authors.affiliation: PharmaIN Corporation, 19805 North Creek Parkway, Suite 200, Bothell, Washington, 98011, USA, gcastillo@pharmain.com.
authors.forename: Gerardo M
authors.initials: GM
authors.lastname: Castillo
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishimoto-Ashfield
authors.forename: Aryamitra A
authors.initials: AA
authors.lastname: Banerjee
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Landolfi
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Lyubimov
authors.forename: Elijah M
authors.initials: EM
authors.lastname: Bolotin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D005755:Gastrins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D009853:Omeprazole / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D005755:Gastrins; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011108:Polymers; D013311:Streptozocin; D009853:Omeprazole