What if gut hormones aren't really hormones: DPP-4 inhibition and local action of GLP-1 in the gastrointestinal tract.

摘要

The pharmacological actions of the GLP-1 receptor agonists are largely predictable from what is known about the physiology of GLP-1. Because these agents are not susceptible to inactivation by DPP-4 and reach supraphysiological levels in the plasma for hours after administration, it has been presumed that they interact directly with GLP-1 receptors on j3-cells to mediate their effects. The mechanism of action of DPP-4 inhibitors is less clear. These orally available small molecules provide substantial inhibition of DPP-4, at least as reflected by reduced activity of the enzyme in plasma and an increased percentage of circulating incretins retained in the intact, bioactive form. However, the absolute concentration of intact GLP-1 during DPP-4 inhibition is limited by the amount of pep-tide secreted from the gut, and levels increase only 1.5- to 3-fold in postprandial plasma (3).