Glucagon-like peptide-1 delivery for treatment of type 2 diabetes

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Title Glucagon-like peptide-1 delivery for treatment of type 2 diabetes
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Choi, Suna
Date 2005-05
Description Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone that increases insulin secretion in a glucose-dependent manner. Insulin secretion is only increased when concentrations of glucose is high and not at low to normal concentrations of glucose, therefore avoiding hypoglycemic episodes. In spite of its many remarkable advantages as a therapeutic agent for diabetes, GLP-1 is not immediately clinically applicable because of its extremely short half-life. The purpose of this research was to design an effective way of GLP-1 delivery for therapeutic use of GLP-1. The first half of the research studied the effects of GLP-1 delivery using a thermosensitive biodegradable triblock copolymer. The second half of this research was to design a new and effective GLP-1 delivery system for therapeutic use for type 2 diabetes treatment based upon construction of GLP-1 plasmid and its delivery. The effect of GLP-1 delivery system using biodegradable injectable polymer was studied. The results from the I release experiment did show steady amount of GLP-1 released from PLGA-PEG-PLGA triblock copolymer formulation with zinc-complexed GLP-1 depot more than ten days after loading. As a result from the animal experiment with the type 2 diabetic model, it was evident that the GLP-1 released from the thermosensitive biodegradable hydrogel formulation was bioactive as it stimulated insulin secretion in vivo. Therefore, it was concluded that it is feasible to use PLGA-PEG-PLGA triblock copolymer formulation with zinc-complexed GLP-1 as a 2 week delivery system, making it a twice-a-month injection depot. For less frequent and more convenient administration of GLP-1, the GLP-1 gene delivery system was attempted in this study. Since no reactive hypoglycemia occurs even with higher concentrations of GLP-1, a potent promoter/enhancer was used in this system. It has been established that GLP-1 gene delivery significantly decreased blood glucose levels in a type 2 diabetic animal model. The results showed that delivered GLP-1 gene stimulated insulin secretion, indicating that GLP-1 gene delivery also represents a promising candidate for treatment of type 2 diabetes.
Type Text
Publisher University of Utah
Subject Insulinotropic; Hydrogel Formulation
Subject MESH Peptides; Pharmacology; Drug Delivery Systems; Polyamines; Diabetes Mellitus
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Glucagon-like peptide-1 delivery for treatment of type 2 diabetes". Spencer S. Eccles Health Sciences Library. Print version of "Glucagon-like peptide-1 delivery for treatment of type 2 diabetes". available at J. Willard Marriott Library Special Collection. RS43.5 2005 .C48.
Rights Management © Suna Choi.
Format application/pdf
Format Medium application/pdf
Format Extent 2,430,001 bytes
Identifier undthes,4522
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 2,430,078 bytes
ARK ark:/87278/s6w097tn
Setname ir_etd
ID 191676
Reference URL https://collections.lib.utah.edu/ark:/87278/s6w097tn
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