Incretin hormones are a group of metabolic hormones produced by the gut in response to food intake. These hormones play an important role in how the body processes nutrients, particularly in regulating blood sugar levels after meals. They are a significant part of the complex communication network between the digestive system and other organs involved in metabolism.
The Primary Incretin Hormones
The two main incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is primarily secreted by L-cells, enteroendocrine cells located predominantly in the distal ileum and colon. GIP is released from K-cells, found mainly in the duodenum and jejunum. Both hormones are released into the bloodstream shortly after nutrients are consumed, initiating a coordinated metabolic response.
The Incretin Effect on Blood Sugar and Digestion
The “incretin effect” describes how orally consumed glucose leads to a much greater insulin response compared to the same amount of glucose delivered intravenously. This phenomenon is largely mediated by GLP-1 and GIP. When food enters the digestive tract, these hormones signal the pancreatic beta cells to release insulin in a glucose-dependent manner, meaning insulin is released only when blood glucose levels are elevated.
Beyond stimulating insulin, incretins also influence glucagon, a hormone produced by the pancreas that raises blood sugar. GLP-1 specifically suppresses glucagon secretion, which helps to further lower blood glucose by reducing the liver’s glucose production.
GLP-1 also plays a role in slowing gastric emptying, the rate at which food moves from the stomach into the small intestine. This deceleration helps to prevent rapid spikes in blood sugar after a meal by controlling the pace at which nutrients are absorbed into the bloodstream. This effect can be a significant mechanism for glucose lowering, even independently of insulin secretion.
The Role in Satiety and Appetite Control
Incretin hormones, especially GLP-1, affect feelings of fullness and appetite. GLP-1 acts on receptors in various brain areas, including the hypothalamus and brainstem, which are regions involved in controlling food intake. This interaction helps to promote satiety, the feeling of being full and satisfied after eating, and can reduce overall food consumption.
The gut-brain axis facilitates this communication, transmitting signals from the digestive tract to the brain. GLP-1 contributes to these signals, helping the brain register a reduction in hunger. Peripheral administration of GLP-1 to humans has been shown to reduce appetite and energy intake in a dose-dependent manner.
Incretins and Metabolic Disease
In individuals with type 2 diabetes, the incretin system often exhibits impaired function. This impairment leads to a reduced incretin effect, meaning the augmented insulin response to oral glucose is significantly diminished compared to healthy individuals. While GIP secretion may be near normal, its ability to stimulate insulin release is often severely compromised.
GLP-1 secretion can also be impaired in type 2 diabetes, although its insulin-stimulating and glucagon-suppressing actions are generally preserved. This dysfunction in the incretin system contributes to the elevated blood sugar levels observed after meals in people with type 2 diabetes. The reduced effectiveness of these hormones means the body struggles to adequately manage incoming glucose.
Therapeutic Use of Incretin Mimetics
Modern medicine leverages the incretin system to manage type 2 diabetes and, increasingly, obesity through specific drug classes. GLP-1 receptor agonists are one such class, designed to mimic the action of natural GLP-1. These injectable medications bind to GLP-1 receptors, stimulating glucose-dependent insulin release, suppressing glucagon secretion, and slowing gastric emptying.
Another class, dipeptidyl peptidase-4 (DPP-4) inhibitors, works by preventing the breakdown of the body’s own GLP-1 and GIP. The enzyme DPP-4 rapidly inactivates these hormones, so inhibiting it allows natural incretin levels to remain active longer, enhancing their effects. These oral medications modestly increase endogenous incretin levels, leading to improved blood sugar control. Both GLP-1 receptor agonists and DPP-4 inhibitors help lower blood glucose, and GLP-1 receptor agonists additionally contribute to weight loss and may offer cardiovascular benefits.