Glucose-dependent insulinotropic polypeptide, or GIP, is a hormone produced within the gastrointestinal tract. Specialized cells called K cells, located in the duodenum and jejunum—the upper parts of the small intestine—release GIP in response to nutrient intake. The presence of carbohydrates and fats from a meal are the primary triggers for its secretion. It belongs to a family of hormones known as incretins, which are a component of the body’s system for managing metabolic processes that follow food consumption. The discovery of GIP was initially based on its ability to inhibit gastric acid, but its more significant function in glucose management was later identified.
The Primary Function of GIP
The principal role of glucose-dependent insulinotropic polypeptide involves its interaction with the pancreas. After a meal, GIP travels through the bloodstream to the pancreatic islets and binds to its specific receptors on beta-cells. This binding prompts the beta-cells to release insulin. This action helps the body’s cells take up glucose from the blood, thereby managing blood sugar levels after eating.
A defining characteristic of this hormone is its “glucose-dependent” nature. GIP’s ability to stimulate insulin secretion is most pronounced when blood glucose levels are high, such as after consuming carbohydrates. This mechanism acts as a safeguard, ensuring insulin is released when needed. When blood sugar levels are normal or low, GIP’s effect on insulin release is diminished, which helps prevent blood sugar from dropping too low.
GIP also has a complex relationship with another pancreatic hormone, glucagon, which is produced by alpha-cells. During conditions of high blood sugar, GIP can help suppress glucagon release. However, under low blood sugar conditions, GIP may stimulate glucagon secretion, demonstrating its role in maintaining glucose balance.
Understanding the Incretin Effect
The function of GIP is a central part of a broader physiological process known as the “incretin effect.” This term describes the observation that insulin secretion is significantly greater when glucose is consumed orally compared to when the same amount is administered intravenously. This difference can account for up to 70% of the insulin response after a meal, highlighting the digestive tract’s importance in regulating blood sugar.
When food is eaten, the gut releases incretin hormones that signal the pancreas to prepare for an influx of glucose. GIP and another hormone, glucagon-like peptide-1 (GLP-1), are the two primary incretins responsible for this amplified insulin response. GLP-1 is secreted from L-cells located further down in the ileum and colon.
Together, these two hormones form the basis of the incretin system. Studies suggest that GIP may be the more dominant incretin hormone in healthy individuals. The combined action of GIP and GLP-1 ensures a coordinated and efficient response to nutrient intake, linking gut absorption directly to pancreatic hormone release.
GIP’s Broader Metabolic Influence
Beyond its role in the pancreas, GIP influences other tissues, playing a part in the body’s overall energy management. GIP receptors are expressed on adipocytes (fat cells), and the hormone is involved in regulating fat metabolism. GIP promotes the storage of fat by enhancing the clearance of triglycerides from the bloodstream and their deposition into adipose tissue. This function helps partition energy from meals, directing dietary fats toward storage.
There is also evidence that GIP has effects on bone metabolism. Research indicates that GIP may promote bone formation by stimulating the proliferation of osteoblasts, the cells responsible for building new bone. Simultaneously, it has been shown to inhibit the activity of osteoclasts, the cells that break down bone tissue. This dual action suggests a role for GIP in maintaining skeletal health.
Harnessing GIP for Medical Treatments
The understanding of GIP’s functions has led to its emergence as a target for therapeutic intervention, particularly for type 2 diabetes and obesity. For years, medical treatments focused on mimicking the effects of GLP-1, with considerable success in improving blood sugar control and promoting weight loss. However, research shows that targeting both the GIP and GLP-1 pathways simultaneously can yield more substantial results.
This has led to the development of a new class of medications known as dual GIP and GLP-1 receptor agonists. These drugs are designed to activate both hormone receptors at the same time. This dual-agonist approach leverages the distinct and complementary actions of both incretins, resulting in a significant effect on glycemic control and body weight.
A prominent example of this class of medication is tirzepatide, which is marketed under brand names like Mounjaro and Zepbound. Clinical trials have demonstrated that tirzepatide leads to significant reductions in both HbA1c, a measure of long-term blood sugar control, and body weight. Patients using these medications have shown significant improvements, with many achieving weight loss of over 10% of their baseline body weight.