Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists.
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SUBMITTER: Uccellatore A
PROVIDER: S-EPMC4575308 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
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Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists.
Uccellatore Annachiara A Genovese Stefano S Dicembrini Ilaria I Mannucci Edoardo E Ceriello Antonio A
Diabetes therapy : research, treatment and education of diabetes and related disorders 20150814 3
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration a ...[more]
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Project description:Glucagon-like peptide 1 (GLP-1) is a natural peptide agonist of the GLP-1 receptor (GLP-1R) found on pancreatic β-cells. Engagement of the receptor stimulates insulin release in a glucose-dependent fashion and increases β-cell mass, two ideal features for pharmacologic management of type 2 diabetes. Thus, intensive efforts have focused on developing GLP-1-based peptide agonists of GLP-1R for therapeutic application. A primary challenge has been the naturally short half-life of GLP-1 due to its rapid proteolytic degradation in vivo. Whereas mutagenesis and lipidation strategies have yielded clinical agents, we developed an alternative approach to preserving the structure and function of GLP-1 by all-hydrocarbon i, i + 7 stitching. This particular "stitch" is especially well-suited for reinforcing and protecting the structural fidelity of GLP-1. Lead constructs demonstrate striking proteolytic stability and potent biological activity in vivo. Thus, we report a facile approach to generating alternative GLP-1R agonists for glycemic control.
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