The human body maintains complex internal balances through various signaling molecules, including hormones. Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) are important messengers in this system. These hormones are integral to the body’s metabolic regulation, particularly in response to food intake. Understanding their functions provides insight into how the body processes nutrients and maintains overall metabolic health.
What Are GIP and GLP-1
GIP, or Glucose-dependent Insulinotropic Polypeptide, is a hormone produced primarily by K-cells in the lining of the duodenum and jejunum, parts of the small intestine. GIP’s release is triggered by the presence of carbohydrates, proteins, and fatty acids in the chyme, the semi-digested food entering the small intestine.
GLP-1, or Glucagon-like Peptide-1, is another hormone secreted by L-cells, which are located mainly in the distal ileum and colon. Like GIP, GLP-1 is released into the bloodstream in response to food consumption. Both GIP and GLP-1 are classified as incretin hormones, meaning they stimulate insulin secretion in a glucose-dependent manner.
How These Hormones Regulate the Body
GIP and GLP-1 exert their effects through specific receptors, the GIP receptor and the GLP-1 receptor. These receptors are found on various cell surfaces, including pancreatic beta cells. When GIP or GLP-1 bind to their receptors, they activate intracellular signaling pathways, which ultimately leads to the release of insulin. This mechanism ensures that insulin is secreted when blood glucose levels are elevated, such as after a meal, helping to lower blood sugar.
This glucose-dependent stimulation of insulin release is known as the “incretin effect.” It means that insulin secretion is significantly greater when glucose is consumed orally compared to when it’s administered intravenously, even if blood glucose levels are similar. The incretin effect is responsible for 50-70% of the insulin secreted after a meal. GIP also plays a role in stimulating glucagon secretion, particularly during hypoglycemia, and is involved in fat accumulation by promoting fatty acid synthesis and reducing fat breakdown in adipose tissue.
GLP-1, in addition to stimulating insulin, also suppresses glucagon release, especially during hyperglycemia. Glucagon normally raises blood glucose, so its suppression contributes to lower blood sugar levels. GLP-1 slows down gastric emptying, which delays the absorption of nutrients and helps to prevent rapid spikes in blood glucose after meals. This slower digestion also contributes to feelings of fullness and reduced appetite, influencing overall food intake.
GIP and GLP-1 in Medical Treatment
The physiological actions of GIP and GLP-1 have led to their use as therapeutic targets in modern medicine. Medications that mimic or enhance the actions of these hormones are often used to manage type 2 diabetes and obesity. These drugs are generally administered as subcutaneous injections, although some oral formulations exist.
One category of these medications is GLP-1 receptor agonists, which include drugs like semaglutide (Ozempic, Wegovy, Rybelsus) and liraglutide (Victoza, Saxenda). These agonists activate the GLP-1 receptor, leading to increased glucose-dependent insulin secretion, suppressed glucagon release, and slowed gastric emptying. They also act on the brain’s appetite centers, reducing hunger and promoting satiety, which contributes to weight loss. GLP-1 receptor agonists have shown benefits beyond blood sugar control and weight reduction, including lowering blood pressure, improving lipid profiles, and reducing the risk of cardiovascular and kidney diseases.
A newer development is dual GIP/GLP-1 receptor agonists, such as tirzepatide (Mounjaro, Zepbound). This medication activates both GIP and GLP-1 receptors, offering a combined effect that can lead to greater reductions in blood sugar and more weight loss compared to GLP-1 receptor agonists alone. Tirzepatide enhances insulin secretion and reduces glucagon levels in a glucose-dependent manner. It also delays gastric emptying and increases satiety, further contributing to its efficacy in weight management. These dual agonists represent a more comprehensive approach to managing metabolic conditions by leveraging the complementary actions of both incretin hormones.