Glucagon-like peptide-1 (GLP-1) is mainly produced by cells in the ileum and colon, known as L cells. It stimulates the release of insulin from pancreatic beta cells in a manner dependent on glucose concentration, contributing to the body's blood sugar regulation. GLP-1 receptors are found extensively in various organs and tissues, including the central nervous system, gastrointestinal tract, cardiovascular system, liver, adipose tissue, and muscles. Consequently, GLP-1 receptor agonists exhibit multiple mechanisms for lowering blood sugar, such as promoting insulin production, enhancing insulin sensitivity, suppressing glucagon secretion, preventing β-cell apoptosis, reducing liver glucose output, curbing appetite, and delaying gastric emptying and intestinal movement. Additionally, within neural tissues, GLP-1 receptor agonists offer protection to nerve cells, address loss of appetite, and improve memory. In the cardiovascular realm, they contribute to enhanced cardiovascular function and reduced inflammation. Therefore, both GLP-1 and its receptor agonists have broad potential in the treatment of diabetes and metabolic-related diseases.
GLP-1 receptor agonist (GLP-1RA) is an incretin medication that mimics the biological effects of natural GLP-1. It remains active for a longer duration by avoiding degradation, thereby regulating blood sugar and playing a role in diabetes treatment.
The Significance of GLP-1 in Liver Energy Metabolism: Studies indicate that elevated GLP-1 in vagotomized mice can prevent the overproduction of very low-density lipoproteins (VLDL) and insulin resistance induced by a high-fat diet. This suggests that GLP-1 plays a crucial role in regulating liver energy metabolism through the enterohepatic circuit.
GLP-1's Regulation of the Stomach and Lower Intestine Relationship: GLP-1 facilitates the interaction between the stomach and lower intestine through intestinal peptides. Research reveals that ghrelin plays a pivotal role in stimulating L cells to release GLP-1. Conversely, GLP-1 secreted from the lower intestine mediates the ileal braking mechanism, reducing gastric emptying and gastric acid secretion.
Life Cycle and Distribution of GLP-1: Intestinal L cells are primarily responsible for the production and release of GLP-1. After being released into the portal circulation, GLP-1 undergoes degradation by dipeptidyl peptidase (DPP)-4. Only 25% of initially secreted GLP-1 reaches the liver, where it undergoes further breakdown. Merely 10%–15% of GLP-1 reaches peripheral target organs, including the pancreas, brain, gastrointestinal (GI) tract, lungs, and heart.
Mechanism of Action of GLP-1: GLP-1, a peptide hormone released by the intestines, communicates with the brain through the blood-brain barrier and interacts with the vagus nerve. It activates the hypothalamus, periventricular organs, and brainstem, including the nucleus tractus solitarius (NTS), thereby regulating feeding, energy/glucose metabolism, and the cardiovascular system.
