Glucagon-like peptide 1 (GLP-1) and Glucagon-like peptide 2 (GLP-2) are gut hormones released by specialized enteroendocrine L-cells in the intestinal tract in response to nutrient intake. Both peptides originate from the proglucagon gene but are processed differently. Once released, both native hormones are rapidly broken down by the enzyme dipeptidyl peptidase-4 (DPP-4), resulting in a very short lifespan. This rapid degradation led scientists to develop modified versions, or analogs, for medical applications to allow them to exert their separate effects on metabolism and the gastrointestinal system.
GLP-1’s Role in Glucose Metabolism and Satiety
Glucagon-like peptide 1 is an incretin hormone, meaning it enhances insulin secretion in a glucose-dependent manner. When glucose levels rise after a meal, GLP-1 stimulates pancreatic beta cells to release insulin, promoting the uptake of sugar from the blood. This effect helps normalize blood glucose without causing hypoglycemia when glucose levels are stable or low.
The hormone also suppresses the secretion of glucagon from pancreatic alpha cells. Glucagon signals the liver to release stored glucose, so inhibiting it prevents the liver from adding more sugar to the bloodstream during a meal-induced glucose spike. This dual action—boosting insulin and lowering glucagon—maintains blood glucose balance.
GLP-1 also influences the digestive process and appetite control. It slows down gastric emptying, which is the rate food moves from the stomach into the small intestine. This deceleration smooths the absorption of nutrients, preventing sharp post-meal blood sugar surges.
The hormone plays a significant part in the feeling of satiety, or fullness, regulating overall food intake. GLP-1 receptors are found in the brain’s appetite centers, and activating these receptors signals the brain to reduce hunger. This central effect, combined with slowing stomach emptying, contributes to a reduction in caloric consumption.
GLP-2’s Function in Intestinal Health and Repair
Glucagon-like peptide 2 is a hormone focused on the health, growth, and function of the gastrointestinal tract. It is considered an intestinotrophic factor because it promotes the growth and repair of the intestinal lining, or mucosa. It stimulates the proliferation of cells in the intestinal crypts while inhibiting the programmed death (apoptosis) of surface epithelial cells.
This cell growth results in a larger surface area within the small intestine, enhancing the capacity for nutrient and fluid absorption. By thickening the mucosal layer, GLP-2 maintains the intestinal barrier function. Strengthening this barrier reduces intestinal permeability, preventing the movement of harmful substances from the gut into the bloodstream.
GLP-2 also influences blood flow to the gut. It increases mesenteric blood flow, supporting the metabolic demand of an actively absorbing intestine. The hormone helps regulate gut motility and acid secretion, optimizing conditions for digestion and nutrient uptake.
Therapeutic Use of GLP-1 Receptor Agonists
GLP-1 receptor agonists are modified versions of the hormone developed for clinical use. These pharmaceutical analogs are engineered to resist degradation by DPP-4, giving them a longer half-life that allows for less frequent dosing, such as once daily or once weekly injections. These agonists mimic native GLP-1 by activating the same receptors throughout the body.
The primary application for these medications is managing Type 2 Diabetes, where they significantly improve glycemic control. They achieve this by stimulating glucose-dependent insulin release and suppressing glucagon secretion, resulting in a reduction in long-term blood sugar markers, such as hemoglobin A1c.
GLP-1 agonists are also effective in chronic weight management. The drugs leverage the central effects of GLP-1 by activating receptors in the brain to reduce appetite and suppress food cravings. Combined with delayed gastric emptying, this leads to a sustained reduction in calorie intake and weight loss in individuals with obesity.
The long-acting nature of these drugs, which include compounds like semaglutide and liraglutide, provides a consistent therapeutic effect on metabolic and appetite pathways. Their use has expanded beyond diabetes, with many formulations approved for treating obesity by promoting sustained feelings of fullness.
Therapeutic Use of GLP-2 Analogs
While GLP-1 analogs target widespread metabolic conditions, GLP-2 analogs focus on severe intestinal disorders. These pharmaceutical compounds, such as teduglutide, are modified to remain active long enough to exert their growth-promoting effects on the gut.
The primary condition treated is Short Bowel Syndrome (SBS), a state of malabsorption occurring when a large portion of the small intestine is removed or non-functional. In SBS, the remaining gut cannot absorb sufficient nutrients and fluids from the diet.
The analog works by stimulating intestinal adaptation, the body’s natural attempt to increase the absorptive capacity of the remaining bowel. By promoting the proliferation of mucosal cells, the analog increases the absorptive surface area of the residual intestine. This trophic effect helps reduce the patient’s reliance on parenteral nutrition, the intravenous feeding required when the gut cannot function adequately.