Academic Journal
Sustained exendin-4 secretion through gene therapy targeting salivary glands in two different rodent models of obesity/type 2 diabetes.
| العنوان: | Sustained exendin-4 secretion through gene therapy targeting salivary glands in two different rodent models of obesity/type 2 diabetes. |
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| المؤلفون: | Giovanni Di Pasquale, Ilaria Dicembrini, Laura Raimondi, Claudio Pagano, Josephine M Egan, Andrea Cozzi, Lorenzo Cinci, Andrea Loreto, Maria E Manni, Silvia Berretti, Annamaria Morelli, Changyu Zheng, Drew G Michael, Mario Maggi, Roberto Vettor, John A Chiorini, Edoardo Mannucci, Carlo M Rotella |
| المصدر: | PLoS ONE, Vol 7, Iss 7, p e40074 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22808093/?tool=EBI; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0040074 |
| URL الوصول: | https://doaj.org/article/b5a58b6ba4de46ae91ab1ee5fd254e6b |
| رقم الانضمام: | edsdoj.b5a58b6ba4de46ae91ab1ee5fd254e6b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0040074 |