Reappraisal of GIP Pharmacology for Metabolic Diseases.

Source:

Trends Mol Med. 2016 May;22(5):359-76. doi: 10.1016/j.molmed.2016.03.005. Epub 2016 Mar 30.

Abstract

Glucagon-like peptide-1 (GLP-1) analogs are considered the best current medicines for type 2 diabetes (T2D) and obesity due to their actions in lowering blood glucose and body weight. Despite similarities to GLP-1, glucose-dependent insulinotropic polypeptide (GIP) has not been extensively pursued as a medical treatment for T2D. This is largely based on observations of diminished responses of GIP to lower blood glucose in select patients, as well as evidence from rodent knockout models implying that GIP promotes obesity. These findings have prompted the belief in some, that inhibiting GIP action might be beneficial for metabolic diseases. However, a growing body of new evidence - including data based on refined genetically modified models and improved pharmacological agents - suggests a paradigm shift on how the GIP system should be manipulated for metabolic benefits.

Finan B¹, Müller TD¹, Clemmensen C¹, Perez-Tilve D², DiMarchi RD³, Tschöp MH⁴.

Author information

• ¹Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
• ²Metabolic Diseases Institute, Division of Endocrinology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
• ³Department of Chemistry, Indiana University, Bloomington, IN, USA.
• ⁴Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Electronic address: matthias.tschoep@helmholtz-muenchen.de.