GLP-1

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<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 ๐œถ-cells (within the pancreas).
<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 ๐œถ-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.
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It is broken down using specific enzymes called prohormone convertases (PCs). 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.
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In healthy individuals, PCEs produce GLP-1 precursors (a glucagon-like peptide) in L-cells and glucagon precursors in ๐œถ-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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In healthy individuals, PCs produce GLP-1 precursors in L-cells and glucagon precursors in ๐œถ-cells. These then are trimmed on the C-terminal side by carboxypeptidase E (CPE), and sometimes the C-terminus is amidated<ref>PMID: 11375130</ref>. 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>.
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 ๐œถ-cells rather than glucagon<ref>PMID: 34280055</ref>.
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 ๐œถ-cells rather than glucagon<ref>PMID: 34280055</ref>.

Revision as of 21:09, 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

  1. โ†‘ Mรผller 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, Tschรถp MH. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019 Dec;30:72-130. PMID:31767182 doi:10.1016/j.molmet.2019.09.010
  2. โ†‘ doi: https://dx.doi.org/10.1002/mrc.880
  3. โ†‘ Friis-Hansen L, Lacourse KA, Samuelson LC, Holst JJ. Attenuated processing of proglucagon and glucagon-like peptide-1 in carboxypeptidase E-deficient mice. J Endocrinol. 2001 Jun;169(3):595-602. PMID:11375130 doi:10.1677/joe.0.1690595
  4. โ†‘ 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
  5. โ†‘ 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
  6. โ†‘ Chen XY, Chen L, Yang W, Xie AM. GLP-1 Suppresses Feeding Behaviors and Modulates Neuronal Electrophysiological Properties in Multiple Brain Regions. Front Mol Neurosci. 2021 Dec 17;14:793004. PMID:34975402 doi:10.3389/fnmol.2021.793004
  7. โ†‘ Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. PMID:17928588 doi:10.1152/physrev.00034.2006

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Karsten Theis, Michal Harel

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