Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dipeptidyl peptidase-4 (DPP-4) inhibitors are now a widely used, safe and efficacious class of antidiabetic drugs, which were developed prospectively using a rational drug design approach based on a thorough understanding of the endocrinology and degradation of glucagon-like peptide-1 (GLP-1). GLP-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability. Using the GLP-1/DPP-4 system and type 2 diabetes as an example, this review summarises how knowledge of a peptide's biological effects coupled with an understanding of the pathways involved in its metabolic clearance can be exploited in a rational, step-by-step manner to develop a therapeutic agent, which is effective and well tolerated, and any side effects are minor and largely predictable. Other peptides with metabolic effects which can also be degraded by DPP-4 will be reviewed, and their potential role as additional mediators of the effects of DPP-4 inhibitors will be assessed.
Originalsprog | Engelsk |
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Tidsskrift | Peptides |
Vol/bind | 100 |
Sider (fra-til) | 150-157 |
Antal sider | 8 |
ISSN | 0196-9781 |
DOI | |
Status | Udgivet - feb. 2018 |
ID: 189765215