GLP-1
From Proteopedia
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[[Image:GLP1 helix propensity.PNG|400px]] | [[Image:GLP1 helix propensity.PNG|400px]] | ||
| - | == Synthesis == | + | == Synthesis through proglucagon processing== |
| - | + | <scene name='10/1067195/Proglucagon/1'>Proglucagon</scene> is a prohormone made of 177 amino acids (in humans). In the polypeptide form, it is inactive until processed to yield mature hormones. Proglucagon is found in the human body, specifically in L-cells (within the gut) and 𝜶-cells (within the pancreas). | |
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| + | It is broken down using specific enzymes called prohormone convertases (PCEs). These convertases are endopeptidases (they can act in the middle of an extended peptide), different from exopeptidases DPP-4 and CPE, which also play a role in GLP-1 synthesis and degradation. | ||
| + | In healthy individuals, PCEs produce GLP-1 precursors (a glucagon-like peptide) in L-cells and glucagon precursors in 𝜶-cells. These then are trimmed on the C-terminal side by carboxypeptidase E (CPE), and sometimes the C-terminus is amidated. Other pathways of proglucagon yield other products such as GRPP, and IP-1 in the pancreas and Glicentin, GRRP, Oxyntomodulin, and GLP-2 in the intestines <ref>PMID: 19116373</ref>. | ||
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| + | Glucagon and GLP-1 work to balance the levels of sugar in the blood. However, when a person has type 2 diabetes, they struggle to lower blood sugar on their own, due to a resistance to insulin. As a result of diabetes, proglucagon processes differently in order to adapt. For people with type 2 diabetes, proglucagon may yield GLP-1 in 𝜶-cells rather than glucagon<ref>PMID: 34280055</ref>. | ||
== Degradation == | == Degradation == | ||
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== Binding to receptor == | == Binding to receptor == | ||
| - | GLP-1 binds to the extracellular side of | + | GLP-1 binds to the extracellular side of its receptor, [[GPL-1R]], a G-protein coupled receptor. When <scene name='84/841095/Cv1/1'>bound to the receptor</scene>, GLP-1 acts as agonist. |
== Consequences of receptor binding == | == Consequences of receptor binding == | ||
Revision as of 19:00, 20 December 2024
Glucagon-like peptide 1 (GLP-1) is a hormone involved in insulin regulation. It was discovered when researchers found that glucose in the digestive tract led to higher insulin levels than the same amount of glucose administered directly in the blood stream[1]. GLP-1 is produced in specialized cells in the intestine and in the pancreas, is released into the blood and has effects on cells in the pancreas, in the brain, and in many other organs. The half-life of GLP-1 is on the order of minutes, so it exerts a short-term effect unless continuously produced.
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References
- ↑ Müller TD, Finan B, Bloom SR, D'Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ, Stemmer K, Tang-Christensen M, Woods SC, DiMarchi RD, Tschöp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019 Dec;30:72-130. PMID:31767182 doi:10.1016/j.molmet.2019.09.010
- ↑ Ali S, Drucker DJ. Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes. Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E415-21. PMID:19116373 doi:10.1152/ajpendo.90887.2008
- ↑ Ramzy A, Kieffer TJ. Altered islet prohormone processing: a cause or consequence of diabetes? Physiol Rev. 2022 Jan 1;102(1):155-208. PMID:34280055 doi:10.1152/physrev.00008.2021
