Glucagon-like peptide-1 (GLP-1) was the second incretin to be identified in 1983, with the first identified incretin being gastric inhibitory peptide (GIP), which inhibits the secretion of gastric acid.
GLP-1 is a peptide hormone that consists of 30 or 31 amino acids and is secreted primarily by three different tissues in the human body including enteroendocrine cells in the distal intestine, alpha cells in the pancreas, and the central nervous system. GLP-1 interacts with the GLP-1 receptor (GLP-1R) and is crucial in regulating glucose homeostasis. Apart from the pancreas, GLP-1R is also widely distributed in various body tissues, including the lungs, kidneys, central nervous system, cardiovascular system, gastrointestinal tract, and skin and vagus nerves. This distribution breadth of GLP-1R further highlights the diversity and importance of its biological functions.
GLP-1 is primarily released in response to meals and its concentrations are low when fasting. One of the most critical functions of GLP-1 is to act as an incretin hormone, which amplifies insulin secretion in response to hormones released from the gastrointestinal tract. In healthy individuals, oral glucose administration leads to a two- to threefold larger insulin response than intravenous glucose administration. However, the degree of amplification varies with the amount of glucose consumed and is smaller with lower amounts of glucose. GLP-1 is released after meals and helps to increase insulin secretion, while also inhibiting glucagon secretion. This helps to limit post-meal blood sugar spikes. Further important effects of GLP-1 include inhibition of gastrointestinal secretion and motility. It was noted that GLP-1 inhibits gastrin-induced acid secretion in humans, and subsequently demonstrated that GLP-1 also inhibits meal-induced secretion as well as gastric emptying and pancreatic secretion. Moreover, GLP-1 receptors are expressed in many regions of the brain and in particular in the arcuate nucleus and other hypothalamic regions involved in the regulation of food intake.
GLP-1 receptor agonists (GLP-1RAs) are commonly used to treat type 2 diabetes (T2DM) because of their beneficial effects on weight loss, islet beta cell protection and proliferation, and minimal side effects. The therapeutic applications and potential value of GLP-1RAs in diseases other than diabetes have become a research hotspot. Interestingly, GLP-1RAs have been found to activate the metabolism of brown fat and increase energy expenditure through exercise activities independent of the sympathetic nervous system pathway. Furthermore, GLP-1RAs have been shown to benefit vascular endothelial cells by reducing the risk of cardiovascular events, lowering blood pressure, improving microvascular function, and reducing inflammation. In addition, GLP-1RAs have been found to have neuroprotective effects by stimulating the differentiation of nerve cells and inhibiting neuroinflammation. They have also been reported to inhibit liver inflammation. These findings suggest that GLP-1RAs, besides treating diabetes, can also be used to treat other diseases, such as certain neurological and cardiovascular diseases, as well as those related to metabolic disorders.
Based on: https://doi: 10.3389/fendo.2021.721135