| Literature DB >> 20498254 |
Byung-Joon Kim1, Jie Zhou, Bronwen Martin, Olga D Carlson, Stuart Maudsley, Nigel H Greig, Mark P Mattson, Ellen E Ladenheim, Jay Wustner, Andrew Turner, Homayoun Sadeghi, Josephine M Egan.
Abstract
Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic beta-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.Entities:
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Year: 2010 PMID： 20498254 PMCID： PMC2939671 DOI： 10.1124/jpet.110.166470
Source DB: PubMed Journal: J Pharmacol Exp Ther ISSN： 0022-3565 Impact factor: 4.030