NDLI: Glucose- and Metabolically Regulated Hepatic Insulin Gene Therapy for Diabetes

Content Provider	Springer Nature Link
Author	Hsu, Paul Yueh Jen Kotin, Robert M. Yang, Ya Wun
Copyright Year	2008
Abstract	The purpose of this study was to examine glucose- and metabolically modulation of insulin secretion by rAAV-mediated gene delivery in vitro and in vivo. A recombinant adeno-associated virus vector (rAAV) containing a furin-mutated human insulin gene, driven by the rat insulin I promoter, was used in this study. Glucose-responsive secretion of human insulin was determined by treating rAAV-transduced Huh7 human hepatoma cells with varying concentrations of glucose, with or without insulin secretagogues. Glucose- and metabolically modulated secretion of human insulin in the streptozotocin (STZ)-induced diabetic mice was assessed by intrahepatic administration of rAAV-polyethylenimine (PEI) complexes, followed by intraperitoneal glucose tolerance test (IPGTT), with or without theophylline.Glucose- and metabolically controlled human insulin secretion was obtained in the rAAV-transduced Huh7 cells. Treatment of STZ-induced diabetic animals with rAAV–polyethylenimine (rAAV-PEI) complexes resulted in production of human insulin and amelioration of hyperglycemia. Co-administration of glucose and theophylline in these animals augmented the secretion of human insulin, demonstrating metabolic modulation of insulin secretion in vivo. Immunohistochemical examination of the liver sections of rAAV-treated mice confirmed the production of human insulin.Glucose- and metabolically controlled hepatic insulin gene therapy was obtained both in vitro and in vivo.
Starting Page	1460
Ending Page	1468
Page Count	9
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	25
Issue Number	6
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2008-02-22
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	diabetes mellitus insulin polyethylenimine recombinant adeno-associated virus regulated gene therapy Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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