Article Text

GLP-1 analogues: a new therapeutic approach to prevent ductopenia in cholangiopathies?
  1. Ulrich Beuers1,
  2. Burkhard Göke2
  1. 1
    Department of Gastroenterology & Hepatology, Academic Medical Center, University of Amsterdam, The Netherlands
  2. 2
    Department of Medicine II, Klinikum Grosshadern, University of Munich, Germany
  1. Professor Ulrich Beuers, Department of Gastroenterology & Hepatology, G4-213, Academic Medical Center, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands; u.h.beuers{at}

Statistics from

Incretins have attracted the attention of the medical community for a century.1 They are secreted from the gastrointestinal tract into the splanchnic circulation in response to nutrient ingestion and enhance glucose-stimulated insulin secretion.2 Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are the two incretins identified in animals and man. They are thought to be responsible for about 50–70% of glucose-stimulated insulin secretion after a meal.2 GLP-1 has attracted particular attention since its identification 20 years ago because of its potent insulinotropic activity, inhibition of glucagon secretion, retardation of gastric emptying and also an anorectic effect. GLP-1 is a post-translational proteolytic product of the proglucagon gene and is formed by enteroendocrine L cells mainly residing in the distal ileum and colon. The effects of GLP-1 on α, β and δ cells of pancreas islets and on other target organs including the lung, heart, kidney, intestine and various regions of the central nervous system are mediated via a specific 7-transmembrane-spanning, G-protein-coupled GLP-1 receptor (GLP-1R).2 In pancreatic β cells, GLP-1 stimulates insulin biosynthesis and secretion via receptor-mediated activation of classic cAMP- and (Ca2+)i-dependent signalling pathways. It also enhances β cell proliferation via protein kinase A (PKA)- and mitogen-activated protein kinase (MAPK)-dependent signalling, and inhibits β cell apoptosis via phosphatidylinositol 3-kinase (PI3K)- and protein kinase B (PKB)/Akt-dependent pathways.2

The active peptide, a GLP-1(7–36) amide, is rapidly …

View Full Text

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles