Peptide Liraglutide's Potential In Insulin Secretion

Peptide Liraglutide’s Potential in Insulin Secretion

Liraglutide is studied for its possible impact on weight and insulin production since it is a glucagon-like peptide-1 receptor agonist (GLP-1 RA). It has been hypothesized that Liraglutide hosts the potential to improve glycemic management through increasing glucose-dependent insulin production from pancreatic beta cells. It may also possibly decrease hepatic glucose synthesis through inhibiting glucagon release from pancreatic alpha cells.

Research into the actions of the peptide suggests it may reduce stomach emptying, leading to enhanced satiety and lower food intake, which might explain the weight reduction seen in animal test models. It may also possibly promote the regeneration of pancreatic beta cells by stimulating their proliferation and differentiation. [i]

Peptide Evolution

Liraglutide’s groundbreaking research began with the discovery of GLP-1, an incretin hormone thought to promote glycemic control and weight management. This finding sparked research into ways to maximize GLP-1’s role in combating obesity and insulin resistance.

Weight and cardiovascular risk variables, including blood pressure and lipid profile, may be affected, as suggested by Liraglutide studies. Its hypothesized mode of action may cover glucose control, weight reduction, and possibly also beta cell regeneration, although this is all only conjecture at this point in the research process.

The Incretin Response to Liraglutide Peptide

Dr. Holst proposes that GLP-1 may have several physiological effects, including the incretin action. [ii] Incretins are a class of metabolic hormones thought to help lower blood glucose levels after being produced by the gastrointestinal (GI) tract.

GLP-1 has been suggested in rat models as a potential essential hormone activating the incretin action alongside glucose-dependent insulinotropic polypeptide (GIP). Despite GIP being 10 times more prevalent in the bloodstream than GLP-1, researchers have suggested that GLP-1 may be more effective in lowering blood sugar.

It is worth noting that some combinations of comparable chemicals may enhance the proposed action of the peptide Liraglutide. In 2007, researchers looked at how sulfonylurea chemicals affected the appearance of the Liraglutide peptide in rat pancreases. Even though “GLP-1 presentation to isolated perfused rat pancreases at low perfusate glucose concentrations normally does not affect insulin secretion,” the research suggested that pre-presentation with sulfonylurea compounds dramatically increased insulin secretion (40, 89). However, “30%-40% of subjects presented with both sulfonyl urea compounds and a GLP-1 agonist (exendin 4) experience, usually mild, hypoglycemia” [ii].

Beta Cells and Liraglutide Peptide

Animal studies have suggested promise for the potential stimulatory effects of glucagon-like peptide-1 (GLP-1) and related peptides like Liraglutide on the development and proliferation of pancreatic beta cells. Additionally, GLP-1-like peptides like Liraglutide may stimulate the development of progenitor cells in the pancreatic duct epithelium into new beta cells. They may also support the prevention of beta cell death. [iii] These results suggest that the ratio of new beta cells being produced to those dying off may be shifted in favor of production.

The idea that Liraglutide may prevent the death of beta cells caused by excessive inflammatory cytokines was supported by a convincing study. Data from animal studies of type 1 diabetes in mice suggests GLP-1 may be a protective factor for islet cells. [iii]

Cardiovascular Function and Liraglutide Peptide

GLP-1 receptors are abundant in the heart and are thought to benefit cardiac function in some situations. Possible protective measures against left ventricular hypertrophy, cardiac remodeling, and heart failure include an increased heart rate and a decreased left ventricular end-diastolic pressure. [iv]

Recent studies suggest that GLP-1 (and related peptides like Liraglutide) may exhibit some protection against heart damage. It seems the peptide may improve glucose absorption in heart muscle, which may help ischemic myocardial cells get the fuel they need to keep working and avoid cell death. This enhanced glucose absorption seems to occur in an insulin-independent way.

Improvements in left ventricular function and decreased systemic vascular resistance have been suggested in canine studies requiring massive infusions of GLP-1. [v] “rGLP-1 significantly enhanced LV and systemic hemodynamics in awake dogs with advanced DCM induced by rapid pacing,” said Nikolaidis and colleagues. Studies suggest increases in myocardial glucose absorption which may possibly result from rGLP-1’s insulin-mimetic and glucagonostatic characteristics. Researchers speculate that rGLP-1 may serve as a positive metabolic adjuvant in decompensated heart failure. [v]

Obesity and Liraglutide Peptide

Research suggests that the presentation of GLP-1 and its analog GLP-1Ras, such as Liraglutide, may have lowered mice’s hunger drive and food intake. Recent research studies in mice have suggested that presenting GLP-1 receptor agonists twice daily may result in slow and steady weight reduction. Long-term weight loss may improve cardiovascular risk variables and lower hemoglobin A1C levels.

Neuroprotection and Liraglutide Peptide

New data suggests that GLP-1 may protect neurons from degenerative effects and boost learning. Liraglutide (GLP-1) has suggested promise in animal studies, with some data suggesting it might improve associative and spatial learning and possibly even reverse some of the learning deficiencies seen in mice with certain genetic defects. Findings implied that learning and memory were significantly improved in GLP-1 receptor overexpressing rats compared to controls. [vi]

Liraglutide, a GLP-1 analog, has been suggested to protect neurons from excitotoxic damage in mouse models, and this protection may extend to rats in a rat model of neurodegeneration by preventing glutamate-induced apoptosis. Researchers speculate that the peptide may encourage neurite outgrowth in laboratory-grown cells. [vii]

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References

[i] National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 16134956, Liraglutide. https://pubchem.ncbi.nlm.nih.gov/compound/Liraglutide.

[ii] Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. doi: 10.1152/physrev.00034.2006. PMID: 17928588. https://pubmed.ncbi.nlm.nih.gov/17928588/

[iii] Tandong Yang, Meng Chen, Jeffrey D. Carter, Craig S. Nunemaker, James C. Garmey, Sarah D. Kimble, Jerry L. Nadler, Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes, Biochemical and Biophysical Research Communications, Volume 344, Issue 3, 2006, Pages 1017-1022, ISSN 0006-291X, https://www.sciencedirect.com/science/article/pii/S0006291X06007066

[iv] Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes. 2005. https://pubmed.ncbi.nlm.nih.gov/15616022/

[v] Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation. 2004 Aug 24;110(8):955-61. https://pubmed.ncbi.nlm.nih.gov/15313949/

[vi] During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ, Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003 Sep; https://pubmed.ncbi.nlm.nih.gov/12925848

[vii] Perry T, Haughey NJ, Mattson MP, Egan JM, Greig NH. Protection and reversal of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J Pharmacol Exp Ther. 2002 Sep;302(3):881-8. doi: 10.1124/jpet.102.037481. PMID: 12183643. https://pubmed.ncbi.nlm.nih.gov/12183643/

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Peptide Liraglutide’s Potential in Insulin Secretion