Evolution of Gliptins Over the Last 5 Years
نویسنده
چکیده
In humans, the two main physiologically important incretin hormones are: (1) GLP-1 and (2) GIP. They not only stimulate insulin secretion, but augment insulin stores by upregulating insulin gene expression, and also all the steps in the biosynthesis of insulin. Another attractive facet of incretins is revealed by animal and in vitro studies, which seem to indicate that both these peptides have b-cell trophic effects, while GLP-1 also suppresses glucagon secretion and inhibits gastric emptying, appetite and therefore, caloric intake. These peptides have, however, limited clinical usefulness themselves because they are rapidly degraded by the enzyme DPP4, which severely limits their duration of action. The development of DPP-4-resistant GLP-1 analogues (incretin mimetics) and DPP4 inhibitors (incretin enhancers) were logically proposed as an alternative means of exploiting the full therapeutic potential of this “incretin-axis”. The inhibitors of the DPP-4 enzyme, which rapidly degrades the two major gastrointestinal hormones into inactive products, the “gliptins” increase the levels of the incretin hormones GLP-1 and GIP. The pharmacology of these drugs is based on very sound principles and this is why the gliptins are considered such attractive molecules for clinical use.
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