Glucose-dependent Insulinotropic Polypeptide Receptor (GIP)
Glucose-dependent Insulinotropic Polypeptide Receptor (GIP)
The Glucose-dependent Insulinotropic Polypeptide Receptor (GIPR) plays a significant role in glucose metabolism and fat metabolism in the body. GIP primarily acts as an insulinotropic agent, stimulating insulin release and synthesis. This action depends on increased levels of circulating glucose, making it an important part of the entero-insular axis (the connection between the gut and pancreatic islets), which integrates nutrient-derived signals to control food intake and energy assimilation.1
Although its primary function is as an insulinotropic agent, GIP is also secreted from the upper small intestine in response to food intake, particularly carbohydrates. Secretion is influenced by factors such as meal content and health status (obesity, diabetes, age). The secretion mechanisms involve several nutrient sensors in the intestinal epithelium, including sodium-coupled glucose uptake through SGLT1 and free-fatty acid receptors2.
In addition to stimulating insulin release, GIP amplifies the effect of insulin on target tissues, including adipose tissue. It has been shown to stimulate fatty acid synthesis, enhance insulin-stimulated incorporation of fatty acids into triglycerides, increase insulin receptor affinity, and improve the sensitivity of insulin-stimulated glucose transport.1
The GIP receptor is a G-protein-coupled receptor and is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex, and brain, indicating potential diverse functions beyond glucose and fat metabolism.1 This is beginning to be seen in the many clinical studies continuing around the dual-agonist weight management pharmaceutical treatments.
The GIP Receptor is critical in regulating glucose and fat metabolism, primarily through its insulinotropic effects and interactions with adipose tissue.
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