Reappraisal of GIP Pharmacology for Metabolic Diseases

Trends Mol Med. 2016 May;22(5):359-376. 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Gastric Inhibitory Polypeptide / metabolism
  • Gastric Inhibitory Polypeptide / pharmacology*
  • Gastric Inhibitory Polypeptide / physiology*
  • Glucagon-Like Peptide 1 / pharmacology
  • Humans
  • Insulin / metabolism
  • Metabolic Diseases / drug therapy*
  • Mice
  • Obesity / complications
  • Obesity / drug therapy
  • Receptors, Gastrointestinal Hormone / agonists
  • Receptors, Gastrointestinal Hormone / antagonists & inhibitors
  • Receptors, Gastrointestinal Hormone / metabolism

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Gastrointestinal Hormone
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • gastric inhibitory polypeptide receptor