Glucagon-like peptide-1

Glucagon-like peptide-1 (GLP-1) is a neuropeptide and an incretin derived from the transcription product of the proglucagon gene. The major source of GLP-1 in the periphery is the intestinal L cell that secretes GLP-1 as a gut hormone; the major source in the brain is the nucleus of the solitary tract, which is the source of a widely distributed set of GLP-1 projection neurons. 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 molecule.

GLP-1 secretion by ileal L cells is dependent on the presence of nutrients in the lumen of the small intestine. The secretagogues (agents that cause or stimulate secretion) of this hormone include major nutrients like carbohydrate, protein and lipid. 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.

GLP-1 is a potent antihyperglycemic hormone, inducing the β-cells of the pancreas to release the hormone insulin in response to rising glucose, while suppressing glucagon secretion. Such glucose-dependent action is particularly attractive because an unregulated release of the hormone when the plasma glucose concentration is in the normal fasting range, or poorly-timed insulin injections, can cause a dangerous fall in blood glucose (hypoglycemia). This does not happen as a result of GLP-1 because GLP-1 no longer stimulates the β-cells to release more insulin when blood glucose levels are in the fasting range. Additionally, GLP-1 appears to restore the glucose sensitivity of pancreatic β-cells. The mechanism may involve increased expression of GLUT2 receptors on the surface of the β-cells; GLUT-2 is a carrier protein on the cell surface that facilitates the movement of plasma glucose across the cell membrane, allowing them to sense the level of glucose in circulation and release insulin when levels begin to climb. GLP-1 may also sensitize β-cells by increasing the expression of glucokinase, an enzyme in the β-cells that stimulates insulin production and release in response to glucose entering the cell. GLP-1 is also known to inhibit the programmed cell death (apoptosis) of pancreatic β-cells, and to stimulate β-cell proliferation and differentiation. In addition, GLP-1 inhibits gastric secretion and motility. This delays and protracts carbohydrate absorption and contributes to a satiating effect.

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