Glucagon-Like Peptide-1 (GLP-1) Hormone
A Glucagon-Like Peptide-1 (GLP-1) Hormone is an incretin hormone that is a peptide hormone containing 30-31 amino acids that regulates blood glucose levels through glucose-dependent insulin secretion (from intestinal enteroendocrine L-cells).
- AKA: GLP-1, Glucagon-Like Peptide-1, GLP-1 Hormone, Incretin GLP-1.
- Context:
- It can typically function as an Incretin Hormone through glucose-dependent insulin secretion.
- It can typically regulate Blood Glucose Levels through insulin secretion enhancement.
- It can typically inhibit Glucagon Release from pancreatic alpha cells.
- It can typically slow Gastric Emptying through gastrointestinal motility regulation.
- It can typically reduce Food Intake through appetite regulation mechanisms.
- It can typically be produced by Intestinal Enteroendocrine L-Cells in intestinal mucosa.
- It can typically be produced by Solitary Tract Neurons in brainstem nucleus.
- It can typically undergo Posttranslational Processing from proglucagon peptide.
- It can typically be degraded by Dipeptidyl Peptidase-4 (DPP-4) with rapid enzymatic cleavage.
- It can typically maintain Biological Half-Life of approximately 2 minutes.
- It can typically reach Fasting Plasma Levels of 0-15 pmol/L.
- It can typically act through GLP-1 Receptors on target cells.
- ...
- It can often activate Adenylate Cyclase through G-protein coupling.
- It can often increase Cyclic AMP Levels in pancreatic beta cells.
- It can often enhance Beta Cell Proliferation through growth signaling pathways.
- It can often inhibit Beta Cell Apoptosis through survival signaling.
- It can often have only 10-15% reach Systemic Circulation intact.
- It can often be degraded by Neutral Endopeptidase 24.11 (NEP 24.11).
- It can often undergo Renal Clearance through kidney filtration.
- It can often be secreted via Glucose-Dependent Mechanisms and glucose-independent mechanisms.
- It can often be stored in Synaptic-Like Microvesicles within beta cells.
- It can often be co-localized with Insulin in large dense-core vesicles.
- ...
- It can range from being a Full-Length GLP-1 (1-37) to being a Truncated Active GLP-1 Form, depending on its proteolytic processing state.
- It can range from being an Intact Circulating GLP-1 to being a Degraded GLP-1 Fragment, depending on its enzymatic degradation level.
- It can range from being a Basal GLP-1 Level to being a Postprandial GLP-1 Level, depending on its nutritional state timing.
- It can range from being a Native GLP-1 to being a Modified GLP-1 Analog, depending on its structural modification status.
- ...
- It can exist in Active Forms including GLP-1 (7-36) amide and GLP-1 (7-37).
- It can maintain Protein Secondary Structure with alpha helixes at positions 13-20 and 24-35.
- It can be targeted by GLP-1-Based Therapeutics for type 2 diabetes treatment.
- It can interact with GIP (Glucose-Dependent Insulinotropic Polypeptide) as co-incretin hormone.
- It can be involved in Cardiovascular Protection through endothelial function improvement.
- It can contribute to Neuroprotection through neuronal survival signaling.
- It can influence Bone Metabolism through bone formation promotion.
- It can affect Lipid Metabolism through lipolysis regulation.
- It can modulate Inflammation through anti-inflammatory signaling.
- ...
- Example(s):
- Native GLP-1 Forms, such as:
- GLP-1 (1-37), the initial proglucagon-derived product.
- GLP-1 (7-36) Amide, the most abundant truncated active form with equipotent activity.
- GLP-1 (7-37), another truncated active form with biological activity.
- GLP-1 (9-36) Amide, a DPP-4 degradation product with limited activity.
- GLP-1-Based Therapeutic Targets, such as:
- GLP-1 Receptor Agonists, which mimic GLP-1 hormone action:
- Short-Acting GLP-1 Receptor Agonists, such as:
- Long-Acting GLP-1 Receptor Agonists, such as:
- Dual Incretin Receptor Agonists, such as:
- Tirzepatide (Mounjaro/Zepbound), a dual GIP/GLP-1 receptor agonist.
- Survodutide, an investigational dual glucagon/GLP-1 receptor agonist.
- Retatrutide, an investigational triple GIP/GLP-1/glucagon receptor agonist.
- DPP-4 Inhibitors, which prevent GLP-1 degradation:
- Sitagliptin (Januvia), preventing endogenous GLP-1 breakdown.
- Saxagliptin (Onglyza), extending native GLP-1 half-life.
- Linagliptin (Tradjenta), preserving physiological GLP-1 levels.
- GLP-1 Receptor Agonists, which mimic GLP-1 hormone action:
- GLP-1 Research Applications, such as:
- GLP-1 Biomarker Study, investigating metabolic disease progression.
- GLP-1 Signaling Research, exploring intracellular pathway mechanisms.
- GLP-1 Gene Therapy, developing sustained GLP-1 expression methods.
- ...
- Native GLP-1 Forms, such as:
- Counter-Example(s):
- Glucose-Dependent Insulinotropic Polypeptide (GIP), which is a different incretin hormone with distinct receptor specificity and tissue distribution.
- Glucagon, which increases blood glucose levels rather than decreasing them through hepatic glucose production.
- Insulin, which is not an incretin and works through glucose-independent mechanisms with different secretion patterns.
- Proglucagon, which is the precursor peptide rather than the active hormone form.
- Somatostatin, which inhibits both insulin and glucagon but is not an incretin hormone.
- Amylin, which is co-secreted with insulin but has different metabolic effects.
- See: Incretin Hormone, Peptide Hormone, Type 2 Diabetes, Enteroendocrine Cell, Proglucagon, Dipeptidyl Peptidase-4, GLP-1 Receptor, Insulin Secretion, Pancreatic Beta Cell, Blood Glucose Regulation, GLP-1 Receptor Agonist, Metabolic Syndrome, Obesity Treatment, Cardiovascular Disease, Diabetic Complication, Glucose-Dependent Insulinotropic Polypeptide (GIP).
References
References
2024
- (Wikipedia, 2024) ⇒ https://en.wikipedia.org/wiki/Glucagon-like_peptide-1 Retrieved:2024-5-21.
- Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
Alongside glucose-dependent insulinotropic peptide (GIP), GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective effects. Unlike GIP, the action of GLP-1 is preserved in patients with type 2 diabetes. Glucagon-like peptide-1 receptor agonists gained approval as drugs to treat diabetes and obesity starting in the 2000s.
Endogenous GLP-1 is rapidly degraded primarily by dipeptidyl peptidase-4 (DPP-4), as well as neutral endopeptidase 24.11 (NEP 24.11) and renal clearance, resulting in a half-life of approximately 2 minutes. Consequently, only 10–15 % of GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to increase GLP-1 activity. As opposed to common treatment agents such as insulin and sulphonylurea, GLP-1-based treatment has been associated with weight loss and a lower risk of hypoglycemia, two important considerations for patients with type 2 diabetes.
- Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
2024
- perpepixity
++ Glucagon-Like Peptide-1 (GLP-1) is a hormone produced by the intestinal L-cells in response to food intake. There are two main biologically active forms of GLP-1:
1. GLP-1 (7-36) amide: This is the predominant form, constituting over 80% of circulating GLP-1 in humans. It is produced by the cleavage and amidation of the initial GLP-1 (1-37) product.[1][2]
2. GLP-1 (7-37): This form is equipotent to GLP-1 (7-36) amide but makes up a smaller proportion of circulating GLP-1.[1][2]
Both these forms are rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), resulting in a very short half-life of around 2 minutes.[1][2] To overcome this, GLP-1 receptor agonists (e.g., liraglutide, semaglutide) and DPP-4 inhibitors have been developed as therapeutic agents for diabetes and obesity.[1][2]
In summary, the two main biologically active forms of the GLP-1 hormone are GLP-1 (7-36) amide and GLP-1 (7-37), with the former being the predominant circulating form in humans.[1][2]
Citations: [1] Glucagon-like peptide 1 - You and Your Hormones https://www.yourhormones.info/hormones/glucagon-like-peptide-1/ [2] Glucagon-like peptide-1 - Wikipedia https://en.wikipedia.org/wiki/Glucagon-like_peptide-1 [3] Glucagon-Like Peptide 1 Secretion by the L-Cell | Diabetes https://diabetesjournals.org/diabetes/article/55/Supplement_2/S70/12058/Glucagon-Like-Peptide-1-Secretion-by-the-L-CellThe [4] Glucagon-like peptide 1 (GLP-1): a potent gut hormone with a ... https://pubmed.ncbi.nlm.nih.gov/9840447/ [5] GLP-1 Agonists - Cleveland Clinic https://my.clevelandclinic.org/health/treatments/13901-glp-1-agonists
2023
- (Wikipedia, 2023) ⇒ https://en.wikipedia.org/wiki/Glucagon-like_peptide-1 Retrieved:2023-1-23.
- Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
Alongside glucose-dependent insulinotropic peptide (GIP), GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective effects. Unlike GIP, the action of GLP-1 is preserved in patients with type 2 diabetes and substantial pharmaceutical research has therefore been directed towards the development of GLP-1-based treatment.
Endogenous GLP-1 is rapidly degraded primarily by dipeptidyl peptidase-4 (DPP-4), as well as neutral endopeptidase 24.11 (NEP 24.11) and renal clearance, resulting in a half-life of approximately 2 minutes. Consequently, only 10–15 % of GLP-1 reaches circulation intact, leading to fasting plasma levels of only 0–15 pmol/L. To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to increase GLP-1 activity. As opposed to common treatment agents such as insulin and sulphonylurea, GLP-1-based treatment has been associated with weight loss and a lower risk of hypoglycemia, two important considerations for patients with type 2 diabetes.
- Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
2023
- (Wikipedia, 2023) ⇒ https://en.wikipedia.org/wiki/Incretin Retrieved:2023-12-24.
- Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
Some incretins (GLP-1) also inhibit glucagon release from the alpha cells of the islets of Langerhans. In addition, they slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying and may directly reduce food intake. The two main candidate peptides that fulfill criteria for an incretin are the intestinal peptides glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP, also known as: glucose-dependent insulinotropic polypeptide). GIP is produced and secreted into the blood circulation by K cells, i.e., single cells located in the mucosa of the upper gastrointestinal tract's duodenum and upper jejunum while GLP1 is produced and secreted into the blood by L cells located in the mucosa of the lower gastrointestinal tracts small and large intestines.[1] Short-chain fatty acids (primarily acetic, propionic, and butyric acids), which microganisms form in the intestines, bind to the FFAR2 and FFAR3 receptors on K cells and L cells to stimulate their respective production and secretion of GIP and GLP-1. Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4) and are members of the glucagon peptide superfamily.
- Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism.
- ↑ Cite error: Invalid
<ref>tag; no text was provided for refs namedpmid29364588