Glucose-dependent insulinotropic polypeptide (GIP)
Timo D. Müller, Alice E. Adriaenssens, Bo Ahrén, Matthias Blüher, Andreas L. Birkenfeld, Jonathan E. Campbell, Matthew P. Coghlan, David D’Alessio, Carolyn F. Deacon, Stefano DelPrato, Jonathan D. Douros, Daniel J. Drucker, N. Burgos, Peter R. Flatt, Brian Finan, Ruth E. Gimeno, Fiona M. Gribble, Matthew R. Hayes, Christian Hölscher, Jens J. Holst, Patrick J. Knerr, Filip K. Knop, Christine M. Kusminski, Arkadiusz Liśkiewicz, Guillaume Mabilleau, Stephanie A. Mowery, Michael A. Nauck, Aaron Novikoff, Frank Reimann, Anna G Roberts, Mette M. Rosenkilde, Ricardo J. Samms, Philip E Scherer, Randy J. Seeley, Kyle W. Sloop, Christian Wolfrum, Denise Wootten, Richard D. DiMarchi, Matthias H. Tschöp
Abstract
BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP. SCOPE OF REVIEW: In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases. MAJOR CONCLUSIONS: Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.