Glucagon-like peptide 1, also known as GLP1, is a hormone produced in the gut and released in reaction to food is called glucagon-like peptide 1. It reduces appetite and helps in the release of insulin
The hormone glucagon-like peptide 1 is a member of the incretin hormone family, so named because it increases insulin secretion due to stimuli from the gut. GLP 1 is the product of a pre-proglucagon molecule, a polypeptide (i.e., a chain of amino acids, which are organic molecules that makeup proteins) that is divided to create several hormones, including glucagon. These hormones are referred to as "glucagon-like" since they share similarities and derive from the same source. Although it is secreted in lower amounts by the pancreas and the central nervous system, the small intestine's L-cells are the primary source of glucagon-like peptide 1. In addition to increasing the number of insulin-producing beta cells in the pancreas and decreasing glucagon release, glucagon-like peptide 1 promotes insulin release from the pancreas. Through its effects on the brain's appetite centers and its ability to delay stomach emptying, glucagon-like peptide 1 also intensifies the sensation of fullness during and between meals.
The primary trigger for glucagon-like peptide 1 release is food, which causes levels to rise within 10 to 15 minutes of eating and stay elevated for several hours later. In addition to meals, nerve stimulation and other hormones can influence the production of glucagon-like peptides. Somatostatin, a hormone, lowers glucagon-like peptide 1 synthesis. Dipeptidyl peptidase-4 is an enzyme that quickly degrades glucagon-like peptide 1.
Too little glucagon-like peptide 1 released after a meal may aggravate or raise the risk of obesity. A person may eat more during a meal and be more likely to snack between meals if their body produces less glucagon-like peptide 1, which decreases appetite after meals.
No cases of excessive glucagon-like peptide 1 are known to exist. To help type-2 diabetics better control their blood glucose levels, medications that mimic the actions of glucagon-like peptide 1 in the bloodstream have been created. These medicines are referred to as GLP-1 analogs. After various weight-related surgeries, levels of glucagon-like peptide 1 are also naturally elevated, which is likely to have a role in the observed weight loss and improvement of type-2 diabetes in people who have undergone these procedures. Recently, the UK and other nations legalized using one of these GLP-1 analogs (liraglutide) to treat obesity. Other GLP-1 analogs are being studied in the research, and they might one day be licensed to treat obesity.
The GI tract performs various functions, including food digestion, nutrient absorption, and the release of digestive juices, mucus, and peptide hormones. A variety of cell types, including enteroendocrine cells, a vital part of the gut-brain-pancreas axis, make up the epithelium of the GI wall.
Enteroendocrine cells have microvilli on their apical surfaces that express several receptors that bind to nutrients and other substrates in the GI lumen.
Enteroendocrine cells can be classified into many subcategories. It may depend on how they are distributed throughout the GI tract, the expression of their receptors, and their secretory characteristics. A significant percentage of the GI tract, beginning in the proximal small intestine and gradually increasing in density down to the distal part of the colon, is expressed with enteroendocrine L-cells, which produce and secrete GLP-1.
GLP-1 uses endocrine and neuronal routes to exert its effects in the pancreas and central nervous system after being stored in secretory granules of L-cells until its release is triggered. In addition to L-cells, neurons in the brainstem's nucleus tractus solitarius (NTS) also produce GLP-1, but to a lesser amount.
Two primary active forms of GLP-1, GLP-1 (7-36 amide) and GLP-1 (7-37 amide), are generated due to the differential processing of proglucagon, the hormone's precursor.
The tissue-specific expression of pro-hormone convertases 1 and 3, which cleave proglucagon, appears to be responsible for its production. Proglucagon is a 160-amino acid precursor that is inactive in several peptide hormones, including oxyntomodulin, glucagon, and GLP-1.
The intestine, the pancreas, and the central nervous system all express the proglucagon-encoding gene. Numerous investigations have demonstrated that this gene expresses similar messenger ribonucleic acid (mRNA) transcripts in these critical locations, which are then translated and processed differently depending on the expressing tissue to create various bioactive peptides.
Blood levels of GLP-1 in individuals typically fluctuate between 5 pmol/L and 15 pmol/L, whereas they rise two to four-fold after eating.
More specifically, 15 minutes after eating, GLP-1 blood concentrations begin to climb and peak 60 minutes later. GLP-1 levels steadily decline in the second hour until the subsequent prandial episode. Nutritional and neuroendocrine factors impact postprandial GLP-1 secretion, which has a two-phase release profile similar to insulin.
The proximal small intestine's L-cells and nutrients are hypothesized to interact with each other to a reduced extent during the initial phase of its secretion, which is observable 10 to 15 minutes after food ingestion. On the other hand, the second phase of GLP-1 secretion, which takes place 30 to 60 minutes postprandially, is primarily regulated by the entry of nutrients into the colon and distal region of the small intestine.
By activating intracellular pathways, nutrients and their by-products bind to receptors and cause GLP-1 exocytosis from the secretory granules of L-cells. When released, GLP-1 can stimulate vagal afferent nerve fibers, diffuse into adjacent capillaries, and then travel through the portal vein to enter the systemic circulation. GLP-1 is exceptionally vulnerable to the catalytic activity of the enzyme dipeptidyl-peptidase IV in circulation (DPP-IV). The latter breaks down the two NH2-terminal amino acids of the physiologically active GLP-1 forms, 7-36 amide and 7-37 amide, resulting in their synthesis as 9-36 amide and 9-37 amide. As a result, GLP-1 has a relatively brief half-life of just 1 to 2 minutes.
Less than 25% of the freshly released bioactive GLP-1 makes it to the liver intact. Only around 10-15% of newly produced GLP-1 reaches systemic circulation in active forms because different enzymatic processes occur in the liver.
GLP-1 primarily acts as an incretin hormone by stimulating insulin secretion and inhibiting glucagon release, which helps reduce postprandial glucose excursions.
GLP-1 has several recognized and potential pancreatic activities. The GLP-1 receptor is expressed in β-cells, and stimulation of this receptor is thought to have both immediate and long-term effects. Regarding β-cell function, GLP-1 potently and quickly increases insulin secretion. However, GLP-1 also promotes neogenesis, islet cell development, and transcription of the insulin gene—other possibly significant processes that may be therapeutically relevant for treating diabetes.
GLP-1 can boost cellular differentiation and enhance islet and beta-cell mass. In vivo experiments provide a clue as to the clinical utility of GLP-1 therapy in preventing the loss of β-cell capacity.
GLP-1 seems to have a variety of non-pancreatic actions. It takes part in the ileal break phenomena by inhibiting stomach emptying and small intestinal transit. Through its direct actions on gastric smooth muscle, GLP-1 reduces stomach motility. It also prevents postprandial acid release. Additionally, it slows down the movement of the small intestine by inhibiting the smooth muscle's ability to contract, generally lowering the number of nutrients absorbed from the GI tract.
Reduced motility likely results in fewer extreme postprandial glucose variations and less need for a big, quick insulin response after meals. GLP-1 also increases skeletal muscle, adipose tissue, and insulin sensitivity. Numerous studies indicate that GLP-1 may directly improve glucose elimination in an insulin-independent manner, albeit this could also result from overall glucagon secretion suppression.
GLP-1 has a significant impact on eating behavior. Although these GLP-1 effects on intestinal motility may contribute to these effects, since GLP-1 receptors are present in certain hypothalamic nuclei, they also appear to have direct effects on eating centers. In humans, acute GLP-1 treatment causes satiety and reduces calorie intake. Exendin 9-39, a GLP-1 antagonist, can reverse the effects of GLP-1 and contribute to weight gain.
Short-term GLP-1 or exendin four treatment in type 2 diabetic people reduces hunger and food intake in addition to its insulinotropic effects, indicating long-term therapy would encourage weight loss in these individuals. Promoting weight loss and enhancing β-cell function by GLP-1 analogs may make them excellent for treating type 2 diabetes.