Systemic Delivery of Bioactive Glucagon-Like Peptide 1 after Adenoviral-Mediated Gene Transfer in the Murine Salivary Gland

Date

2010-09-01

Author

Voutetakis, Antonis
Cotrim, Ana P.
Rowzee, Anne
Zheng, Changyu
Rathod, Trushar
Yanık, Tülin
Loh, Y. Peng
Baum, Bruce J.
Cawley, Niamh X.

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

164
views

5
downloads

Anadenoviral (Ad) vector that expresses bioactive glucagon-like peptide 1 (GLP-1) was generated, and its effectiveness at modulating glucose homeostasis was evaluated after transduction of murine salivary glands. The construct was engineered with the signal sequence of mouse GH to direct the peptide into the secretory pathway, followed by a furin cleavage site and the GLP-1(7-37) sequence encoding an Ala to Gly substitution at position 8 to achieve resistance to degradation. When expressed in Neuro2A and COS7 cells, an active form of GLP-1 was specifically detected by RIA in the conditioned medium of transduced cells, showed resistance to degradation by dipeptidyl-peptidase IV, and induced the secretion of insulin from NIT1 pancreatic beta-cells in vitro. In vivo studies demonstrated that healthy mice transduced with Ad-GLP-1 in both submandibular glands had serum GLP-1 levels approximately 3 times higher than mice transduced with the control Ad-luciferase vector. In fasted animals, serum glucose levels were similar between Ad-GLP-1 and Ad-luciferase transduced mice in keeping with GLP-1's glucose-dependent action. However, when challenged with glucose, Ad-GLP-1 transduced mice cleared the glucose significantly faster than control mice. In an animal model of diabetes induced by alloxan, progression of hyperglycemia was significantly attenuated in mice given the Ad-GLP-1 vector compared with control mice. These studies demonstrate that the bioactive peptide hormone, GLP-1, normally secreted from endocrine cells in the gut through the regulated secretory pathway, can be engineered for secretion into the circulatory system from exocrine cells of the salivary gland to affect glucose homeostasis. (Endocrinology 151: 4566-4572, 2010)

URI

https://hdl.handle.net/11511/93869

Journal

ENDOCRINOLOGY

DOI

https://doi.org/10.1210/en.2010-0193

Collections

Department of Biology, Article

Suggestions

OpenMETU
Core

Metabolic reaction network of Pichia pastoris with glycosylation reactions: Flux analysis for erythropoietin production Eskitoros, Melda S.; Ata, Ozge; Çalık, Pınar (Wiley, 2014-11-01) BACKGROUND: Biochemical reaction network of Pichia pastoris was improved by including N-glycosylation pathway reactions to determine the intracellular reaction rates for glycosylated protein production.
Immobilization of invertase and glucose oxidase in conducting H-type polysiloxane/polypyrrole block copolymers Gursel, A; Alkan, S; Toppare, Levent Kamil; Yagci, Y (Elsevier BV, 2003-01-01) In this study, immobilizations of enzymes, invertase and glucose oxidase, were achieved in conducting copolymers of N-pyrrolyl terminated polydimethylsiloxane/polypyrrole (PDMS/PPy) matrices via electrochemical polymerization. The kinetic parameters, v(max) (maximum reaction rate) and K-m (substrate affinity), of both free and immobilized enzymes were determined. The effect of supporting electrolytes, p-toluene sulfonic acid and sodium dodecyl sulfate, on enzyme activity and film morphologies was examined. ...
Immobilization of invertase, polyphenol oxidase and glucose oxidase n conducting copolymers of thiophene-capped polytetrahydrofuran and pyrrole Böyükbayram, Ayşe Elif; Toppare, Levent Kamil; Department of Chemistry (2005) Immobilization of invertase, polyphenol oxidase (PPO) and glucose oxidase (GOD) enzymes were performed in electrochemically synthesized two types of conducting copolymers. One end and two end thiophene-capped polytetrahydrofuran (TPTHF-1 and TPTHF-2) were copolymerized with pyrrole under conditions of constant potential electrolysis. The copolymers were characterized by thermal, spectroscopic and scanning electron microscopy analyses. Immobilization was carried out via entrapment of enzymes in two types of ...
Differential expressions and functions of phosphodiesterase enzymes in different regions of the rat heart DERİCİ, MEHMET KÜRŞAT; SADİ, GÖKHAN; Cenik, Basar; Güray, Nülüfer Tülün; DEMİREL YILMAZ, EMİNE (Elsevier BV, 2019-02-05) Phosphodiesterase enzymes (PDEs) are responsible for the adjustment of cyclic nucleotide levels. Alterations in PDE expressions in different tissues cause conflicts between functional and clinical effects of PDE inhibitors. Therefore, the aim of this study was to investigate the gene and protein expressions and the functional role of PDEs in atrium and ventricle of rat heart The expressions of PDEs were examined in cardiac intact tissues and enzymatically isolated cells. The effects of PDE1-5 inhibitors (vi...
Immune modulatory effects of pediococcus pentosaceus derived membrane vesicles: mechanism of action and therapeutic applications Alpdündar Bulut, Esin; Gürsel, Mayda; Department of Biology (2018) In our previous studies, we characterized 5 different human gram positive commensal bacteria derived membrane vesicles (MVs) and compared their activity with non-pathogenic E.coli derived membrane vesicles. Results showed that commensal bacteria derived MVs had immunomodulatory properties whereas non-pathogenic E.coli derived membrane vesicles had immune stimulatory properties. In this thesis, we aimed to focus our attention to Pediococcus pentosaceus-derived MVs that displayed the highest immunomodulatory ...

Citation Formats

A. Voutetakis et al., “Systemic Delivery of Bioactive Glucagon-Like Peptide 1 after Adenoviral-Mediated Gene Transfer in the Murine Salivary Gland,” ENDOCRINOLOGY, vol. 151, no. 9, pp. 4566–4572, 2010, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/93869.