GLP-1

From Proteopedia

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Revision as of 20:38, 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.

1 Structure
2 Synthesis through proglucagon processing
3 Degradation
4 Binding to receptor
5 Consequences of receptor binding

Structure

Bound to the GLP-1 receptor, GLP-1 has an that is near glycine in some complexes. In solution, GLP-1 is according to NMR data. Looking at the helix-propensity of the peptide sequence, the N-terminal part of Glp-1 (7-37) is less likely to be alpha-helical than the C-terminal half.

Synthesis through proglucagon processing

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).

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 ^[2].

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^[3].

Degradation

GLP-1 (7-39) is initially by dipeptidyl peptidase IV to yield GLP-1 (9-37) (). For a discussion how this affects the half-life of GLP-1 and synthetic analogs, see the semaglutide article.

Binding to receptor

GLP-1 binds to the extracellular side of its receptor, GPL-1R, a G-protein coupled receptor. When , GLP-1 acts as agonist.

Consequences of receptor binding

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

Proteopedia Page Contributors and Editors (what is this?)

Karsten Theis, Michal Harel

Retrieved from "http://52.214.119.220/wiki/index.php/GLP-1"

@@ Line 16: / Line 16: @@
 == Degradation ==
-GLP-1 (7-39) is initially <scene name='10/1067195/Glp1_only/3'>degraded</scene> by [[dipeptidyl peptidase IV]] to yield GLP-1 (9-37) (<scene name='10/1067195/Glp1_only/2'>detail</scene>).
+GLP-1 (7-39) is initially <scene name='10/1067195/Glp1_only/3'>degraded</scene> by [[dipeptidyl peptidase IV]] to yield GLP-1 (9-37) (<scene name='10/1067195/Glp1_only/2'>detail</scene>). For a discussion how this affects the half-life of GLP-1 and synthetic analogs, see the [[semaglutide]] article.
 == Binding to receptor ==

GLP-1

From Proteopedia

Revision as of 20:38, 20 December 2024

Contents

Structure

Synthesis through proglucagon processing

Degradation

Binding to receptor

Consequences of receptor binding

References

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