Clinical endocrinology and metabolism. Glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide.
The 42 amino acid polypeptide glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is released from intestinal K-cells in response to nutrient ingestion. Based on animal studies, the peptide was initially assumed to act as an endogenous inhibitor of gastric acid secretion. Later it was found that GIP is capable of augmenting glucose-stimulated insulin secretion, and subsequent studies provided evidence that, in humans, the peptide predominantly acts as an incretin hormone. A role for GIP in the regulation of lipid homeostasis and in the development of obesity has been inferred from different animal studies. While GIP strongly stimulates insulin release in healthy humans, the peptide has almost completely lost its insulinotropic effect in patients with type 2 diabetes. This is different from the actions of glucagon-like peptide 1, which stimulates insulin secretion even in the later stages of type 2 diabetes. This suggests that a diminished insulinotropic effect of GIP may contribute to the pathogenesis of type 2 diabetes. This review will summarize the actions of GIP in human physiology and discuss its role in the pathogenesis of type 2 diabetes, as well as the therapeutic options derived from these findings.
Meier
Juris J
JJ
Larry Hillblom Islet Research Center, UCLA School of Medicine, Los Angeles, CA, USA.
Nauck
Michael A
MA
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000502:physiology; D005934:Glucagon / Q000502:physiology; D005947:Glucose / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000502:physiology; D050356:Lipid Metabolism; D010455:Peptides / Q000502:physiology
D005768:Gastrointestinal Hormones; D007328:Insulin; D010455:Peptides; D005749:Gastric Inhibitory Polypeptide; C073320:enterogastrone; D005934:Glucagon; D005947:Glucose