Gastric inhibitory polypeptide (GIP) is a hormone produced in the gut that plays a role in the body’s response to food. It is one of several hormones that help coordinate digestion and nutrient absorption. GIP’s functions extend beyond the digestive system, influencing how the body processes energy and maintains metabolic balance.
Understanding GIP
GIP is classified as an “incretin hormone,” enhancing insulin secretion following nutrient intake. It is synthesized by specialized cells called K-cells, located in the duodenum and jejunum, the upper parts of the small intestine. The release of GIP is primarily triggered by the presence of nutrients, especially fats and carbohydrates, in the gut after a meal.
The discovery of GIP dates back to the early 1970s, initially identified for its ability to inhibit gastric acid secretion, hence its original name, “gastric inhibitory polypeptide”. However, it soon became clear that its most important function was to stimulate insulin release. This led to its alternate and now more recognized name, glucose-dependent insulinotropic polypeptide, while retaining the familiar acronym GIP.
GIP’s Primary Functions
GIP’s main function is to stimulate insulin release from pancreatic beta-cells in a glucose-dependent manner. This means that GIP primarily enhances insulin secretion when blood glucose levels are rising, typically after consuming a meal. This action helps to manage the influx of glucose into the bloodstream, preventing excessive spikes in blood sugar.
This “incretin effect” helps maintain blood sugar balance. Oral glucose intake results in a greater insulin response compared to the same amount of glucose administered intravenously, a difference largely attributed to incretin hormones like GIP. By amplifying insulin release in response to ingested nutrients, GIP ensures that glucose is efficiently taken up by cells for energy or storage, contributing to glucose homeostasis. GIP also promotes the proliferation and survival of pancreatic beta cells, which produce insulin.
Beyond Glucose Regulation
While known for glucose regulation, GIP also influences other physiological processes. It plays a part in fat metabolism, particularly by promoting fat storage within adipose (fat) tissue. It inhibits the breakdown of fats and stimulate the synthesis of new fatty acids, contributing to energy storage after meals.
Emerging research also suggests that GIP may have effects on bone health, with receptors for GIP found in bone cells. This indicates a potential role in bone formation and remodeling. Furthermore, GIP receptors are present in various regions of the brain, suggesting involvement in processes such as appetite regulation and even memory formation. GIP may influence satiety, contributing to the feeling of fullness after eating.
GIP in Metabolic Health and Disease
GIP signaling can be impaired in metabolic disorders, particularly Type 2 Diabetes (T2D). In T2D, the body’s response to GIP is often diminished, a phenomenon known as GIP resistance. This means that even with normal or elevated GIP levels, the pancreatic beta-cells may not release enough insulin to control blood sugar. This impaired GIP action contributes to the poor glucose control observed in T2D.
In obesity, GIP signaling changes are observed. While GIP normally promotes fat storage, excessive GIP secretion or altered GIP sensitivity in obese individuals can contribute to increased fat accumulation. The interplay between GIP and obesity is complex, with some studies suggesting GIP’s role in promoting weight gain, while others indicate that targeting GIP can lead to weight loss.
Targeting GIP for Therapy
GIP’s functions are explored as a target for medical treatments, particularly for Type 2 Diabetes and obesity. GIP receptor agonists have been developed, which are drugs designed to mimic the actions of natural GIP. These agonists enhance insulin secretion and can improve glucose control.
Often, these GIP agonists are combined with glucagon-like peptide-1 (GLP-1) agonists as “dual incretins” or GIP/GLP-1 receptor co-agonists. An example is tirzepatide, which activates both GIP and GLP-1 receptors. These dual-acting medications improve blood sugar levels and promote weight loss in T2D and obesity. The rationale for these combined therapies lies in the complementary actions of GIP and GLP-1, leading to a more robust metabolic benefit compared to targeting either hormone alone. Additionally, GIP receptor antagonists, which block GIP’s action, are also being investigated for reducing fat accumulation and aiding weight loss.