gastric inhibitory peptide signaling pathway

Definition

Target type: biologicalprocess

A G protein-coupled receptor signaling pathway initiated by gastric inhibitory peptide (GIP) binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. [GOC:nhn, PMID:15955806]

Gastric inhibitory peptide (GIP), also known as glucose-dependent insulinotropic polypeptide, is a 42-amino acid peptide hormone that plays a crucial role in regulating glucose homeostasis. It is secreted from K cells in the proximal small intestine in response to the presence of nutrients, particularly glucose and fatty acids. GIP exerts its actions by binding to its cognate G protein-coupled receptor, GIP receptor (GIPR), which is primarily expressed on pancreatic β-cells, as well as other tissues like the brain, heart, and adipose tissue.

Upon GIP binding, GIPR undergoes conformational changes, leading to the activation of heterotrimeric G proteins, specifically the Gs subtype. Activation of Gs stimulates adenylyl cyclase, resulting in the production of cyclic adenosine monophosphate (cAMP). cAMP, in turn, activates protein kinase A (PKA), triggering a cascade of downstream signaling events.

One of the key downstream targets of GIP signaling is the phosphorylation of key proteins involved in insulin secretion. PKA-mediated phosphorylation of specific residues on the ATP-sensitive potassium (KATP) channel leads to its closure, resulting in membrane depolarization and Ca2+ influx. This Ca2+ influx further activates the exocytotic machinery responsible for insulin release from pancreatic β-cells.

GIP also exerts its effects on glucose homeostasis via other mechanisms. It can stimulate glucose uptake and utilization in peripheral tissues, such as skeletal muscle and adipose tissue. Additionally, GIP may play a role in regulating appetite and food intake.

In summary, the GIP signaling pathway is a complex and multifaceted system that plays a crucial role in regulating glucose homeostasis. The pathway involves the activation of GIPR, which triggers a series of intracellular signaling events that ultimately lead to enhanced insulin secretion, increased glucose uptake, and potential modulation of appetite. These actions contribute to the overall regulation of blood glucose levels.'
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Proteins (1)

Compounds (2)