1. Omeprazole and PGC-Formulated Heparin Binding Epidermal Growth Factor Normalizes Fasting Blood Glucose and Suppresses Insulitis in Multiple Low Dose Streptozotocin Diabetes Model
- Author
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Akiko Nishimoto-Ashfield, Gerardo M. Castillo, Jennifer A. Landolfi, Aryamitra Banerjee, Elijah M. Bolotin, and Alexander V. Lyubimov
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Polymers ,Heparin-binding EGF-like growth factor ,Pharmaceutical Science ,Streptozocin ,Article ,Diabetes Mellitus, Experimental ,Mice ,Internal medicine ,Diabetes mellitus ,Gastrins ,medicine ,Animals ,Pharmacology (medical) ,Pancreas ,Omeprazole ,Gastrin ,Pharmacology ,Drug Carriers ,Type 1 diabetes ,geography ,geography.geographical_feature_category ,urogenital system ,Chemistry ,Organic Chemistry ,medicine.disease ,Islet ,Nanostructures ,Endocrinology ,Intercellular Signaling Peptides and Proteins ,Molecular Medicine ,Insulitis ,hormones, hormone substitutes, and hormone antagonists ,Heparin-binding EGF-like Growth Factor ,Biotechnology ,medicine.drug - Abstract
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.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.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.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.
- Published
- 2013