Glucagon-like peptide-1
Encyclopedia
Proglucagon
Proglucagon is a protein that in humans is encoded by the GCG gene.Proglucagon is a precursor of glucagon, and several other components. It is generated in the alpha cells of the pancreas and in the intestinal L cells in the distal ileum and colon...
gene. The major source of GLP-1 in the body is the intestinal
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
L cell that secretes GLP-1 as a gut
Gut (zoology)
In zoology, the gut, also known as the alimentary canal or alimentary tract, is a tube by which bilaterian animals transfer food to the digestion organs. In large bilaterians the gut generally also has an exit, the anus, by which the animal disposes of solid wastes...
hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
. The biologically active forms of GLP-1 are: GLP-1-(7-37) and GLP-1-(7-36)NH2. Those peptides result from selective cleavage of the proglucagon
Proglucagon
Proglucagon is a protein that in humans is encoded by the GCG gene.Proglucagon is a precursor of glucagon, and several other components. It is generated in the alpha cells of the pancreas and in the intestinal L cells in the distal ileum and colon...
molecule.
GLP-1 secretion by ileal L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogue
Secretagogue
A secretagogue is a substance that causes another substance to be secreted. One example is gastrin,, which stimulates the H/K ATPase in the parietal cells...
s (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
, protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
and lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
. Once in the circulation, GLP-1 has a half-life of less than 2 minutes, due to rapid degradation by the enzyme dipeptidyl peptidase-4
Dipeptidyl peptidase-4
Dipeptidyl peptidase-4 , also known as adenosine deaminase complexing protein 2 or CD26 is a protein that, in humans, is encoded by the DPP4 gene.-Function:...
.
It is a potent antihyperglycemic hormone, inducing glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Such glucose-dependent action is particularly attractive because, when the plasma glucose concentration is in the normal fasting range, GLP-1 no longer stimulates insulin to cause hypoglycemia. GLP-1 appears to restore the glucose sensitivity of pancreatic β-cells, with the mechanism possibly involving the increased expression of GLUT2 and glucokinase. GLP-1 is also known to inhibit pancreatic β-cell apoptosis and stimulate the proliferation and differentiation of insulin-secreting β-cells. In addition, GLP-1 inhibits gastric secretion and motility. This delays and protracts carbohydrate absorption and contributes to a satiating effect.
Physiological functions
GLP-1 possesses several physiological properties that make it (and its analogs) a subject of intensive investigation as a potential treatment of diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. The known physiological functions of GLP-1 include:
- increases insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
secretion from the pancreasPancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
in a glucoseGlucoseGlucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
-dependent manner. - decreases glucagonGlucagonGlucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
secretion from the pancreasPancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
by engagement of a specific G protein-coupled receptorG protein-coupled receptorG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
. - increases insulin-sensitivity in both alpha cells and beta cells
- increases beta cells mass and insulin gene expression, post-translational processing and incretion.
- inhibits acid secretion and gastric emptying in the stomachStomachThe stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
. - decreases food intake by increasing satiety in brain.
- promotes insulin sensitivity.
As a proof of the physiological role of GLP-1 in post-prandial insulin secretion, it has been shown that an oral dose of glucose triggers a much higher peak in plasma insulin concentration compared to an intravenous dose.
See also
- Glucagon-like peptide 1 receptorGlucagon-like peptide 1 receptorThe glucagon-like peptide 1 receptor is a human gene which resides on chromosome 6. The protein encoded by this gene is a member of the glucagon receptor family of G protein-coupled receptors.-Ligand specificity:...
- Glucagon-like peptide-2Glucagon-like peptide-2Glucagon-like peptide-2 is a 33 amino acid peptide with the sequence HADGSFSDEMNTILDNLAARDFINWLIQTKITD in humans. GLP-2 is created by specific post-translational proteolytic cleavage of proglucagon in a process that also liberates the related glucagon-like peptide-1 . GLP-2 is produced by the...
- Type 2 diabetes
- GLP-1 analogs : exenatideExenatideExenatide is a medication approved in April 2005 for the treatment of diabetes mellitus type 2. It belongs to the group of incretin mimetics and is manufactured by Amylin Pharmaceuticals and Eli Lilly and Company....
, liraglutideLiraglutideLiraglutide , marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency on July 3, 2009, and by the U.S... - Dipeptidyl peptidase-4Dipeptidyl peptidase-4Dipeptidyl peptidase-4 , also known as adenosine deaminase complexing protein 2 or CD26 is a protein that, in humans, is encoded by the DPP4 gene.-Function:...
- SitagliptinSitagliptinSitagliptin is an oral antihyperglycemic of the dipeptidyl peptidase-4 inhibitor class. It was developed, and is marketed, by Merck & Co...
( a DPP4 inhibitor) - LiraglutideLiraglutideLiraglutide , marketed under the brand name Victoza, is a long-acting glucagon-like peptide-1 analog that has been developed by Novo Nordisk for the treatment of type 2 diabetes. The product was approved by the European Medicines Agency on July 3, 2009, and by the U.S...