Although GLP-1 analogues were created as therapeutic incretins; extra-pancreatic functions of these drugs, as well as native GLP-1, have been broadly recognized. Among them, the hepatic functions are particularly important. Postprandial GLP-1 release contributes to insulin secretion, which represses hepatic glucose production. This indirect effect of GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to determine whether GLP-1 and its analogues possess direct metabolic effects on the liver, as the determination of the existence of direct hepatic effects may advance the therapeutic theory and clinical practice on subjects with insulin resistance. Furthermore, recent investigations on the metabolic beneficial effects of previously assumed "degradation" products of GLP-1, including GLP-128-36 and GLP-132-36, in the liver and elsewhere have drawn intensive attention. Such investigations may further improve the development and the usage of GLP-1 based drugs. Here we have reviewed the current advancement and the existing controversies on the exploration of direct hepatic functions of GLP-1, and presented our perspectives that the direct hepatic metabolic effects of GLP-1 could be a GLP-1 receptor independent event involving Wnt signaling pathway activation.
- GLP-1-based drugs
- GLP-132-36 and GLP-128-36
- Copyright © 2016, American Journal of Physiology-Endocrinology and Metabolism