Dipeptidyl peptidase-4 inhibitor

Inhibitors of dipeptidyl peptidase- 4, also briefly referred to as DPP4 inhibitors Gliptine or incretin enhancers are substances which inhibit the degradation of the hormone glucagon-like peptide 1 (GLP -1) by the enzyme dipeptidyl peptidase 4 ( DPP4 ). They represent a class of agents under the antidiabetics dar.

Metabolic effects of glucagon-like peptide 1

The hormone GLP -1 is one of the incretin hormones. In addition to the islet cells of the pancreas, it is in the upper small intestine, are formed in the distal ileum and colon. In a food intake be dependent on glucose level rises ( incretin effect) and lead to a lowering of blood glucose by increasing insulin secretion from the beta cells and throttles the glucagon alpha cells of the pancreas. Furthermore, it comes about außerpankreatische effects leads to a slower gastric emptying and stimulation of satiety. The activity of the GLP-1 is limited by the degradation of GLP-1 by dipeptidyl peptidase 4 to an inactive metabolite.

Pharmacology of inhibitors of dipeptidyl peptidase 4

Inhibitors of dipeptidyl peptidase 4 prevent the degradation of glucagon-like peptide-1 by inhibiting the degrading enzyme. As a result, insulin secretion increases only by food intake, since only then elevated blood levels exist to GLP-1. This active principle prevents the appearance of a hypo. Medicinal products containing these active substances can be absorbed orally.

Of inhibition

Transition state inhibitors

Transition state inhibitors currently have no therapeutic significance. You interrupt the process of the cleavage of GLP -1 in the active part of the cleaving enzyme DPP 4 During the first step, the formation of intermediate ( a short- existent intermediate state ) is still running, the spatial structure of these inhibitors interfere with the further progression of the cleavage of the substrate.

Inclusion inhibitors

The active center of DPP 4 includes a hydrophobic pocket. This is a region of the enzyme, predominate in the non-polar, non-ionic amino acids. The inclusion inhibitors have a hydrophobic moiety, which has a similar non-polar nature, allowing them to stay in this hydrophobic region of the active site. The inclusion of inhibitor in other parts of the molecule contains one or more positively charged chemical groups, which facilitates the penetration of the negative charge surrounding the active site. The presence of the inhibitor to the active site, thereby preventing cleavage of the GLP- 1 by taking the place of the GLP -1. This process is called competitive inhibition. The inclusion inhibitors currently represent the therapeutically relevant group

Drugs

• Sitagliptin (trade name: Januvia ® and Janumet ® and XELEVIA ® and Velmetia ® as a combination product with metformin )
• Vildagliptin (trade name: Galvus ® and Jalra ® and Eucreas ® and Icandra ® as a combination product with metformin )
• Linagliptin (trade name: Trajenta ®)
• Saxagliptin (trade name: Onglyza ® and Komboglyze ® as a combination product with metformin )
• Alogliptin (currently no Food and Drug )