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Sustained exendin-4 secretion through gene therapy targeting salivary glands in two different rodent models of obesity/type 2 diabetes
- Source :
- PLoS ONE, Vol 7, Iss 7, p e40074 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile.
- Subjects :
- Blood Glucose
Male
Anatomy and Physiology
medicine.medical_treatment
Gene Expression
Adipose tissue
Type 2 diabetes
Weight Gain
Biochemistry
Salivary Glands
Impaired glucose tolerance
Mice
Endocrinology
Viral classification
Receptors, Glucagon
Glucose tolerance test
Multidisciplinary
Salivary gland
medicine.diagnostic_test
Neurochemistry
Gene Therapy
Dependovirus
medicine.anatomical_structure
Medicine
Neurochemicals
Research Article
medicine.medical_specialty
Science
Genetic Vectors
Adipokine
Endocrine System
Diet, High-Fat
Microbiology
Glucagon-Like Peptide-1 Receptor
Virology
Internal medicine
Diabetes mellitus
medicine
Animals
Humans
Obesity
Biology
Nutrition
Diabetic Endocrinology
Clinical Genetics
Endocrine Physiology
Venoms
business.industry
Insulin
Neuropeptides
Genetic Therapy
Glucose Tolerance Test
Diabetes Mellitus Type 2
medicine.disease
Hormones
Rats
Rats, Zucker
Disease Models, Animal
Diabetes Mellitus, Type 2
Exenatide
Peptides
DNA viruses
business
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....7f13388ddc037822036b907cd1a9d205