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The Tech Education > Health > Tirzepatide Peptide Basics
Health

Tirzepatide Peptide Basics

Govind Dhiman
Last updated: 2023/10/28 at 6:50 PM
By Govind Dhiman  - Founder & Editor in Chief Published October 27, 2023
8 Min Read
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Tirzepatide is a synthetic analog of gastric inhibitory polypeptide (GIP). Studies suggest that it was developed with the intention to increase insulin release, and as a result, it may manage type 2 diabetes and non-alcoholic fatty liver disease. Tirzepatide was named after the Greek word for “tiger.” Tirzepatide is a moderately long peptide with 39 amino acids. Research suggests it may promote insulin release from the pancreas by attaching to GIP and GLP-1 receptors (glucagon-like peptide-1 receptors).

Findings imply that Tirzepatide may boost adiponectin levels by as much as 26% when presented over an extended time [i]. Research on the topic suggests that Tirzepatide may decrease sensations of hunger, bring insulin levels down, and raise insulin sensitivity. When taken as a whole, these properties result in a considerable loss of weight, improvement in glucose tolerance, a reduction in fat (adipose) tissue, and a lower risk of cardiovascular disease.

How Exactly Does Tirzepatide Peptide Work?

Tirzepatide, in layperson’s terms, may possibly encourage the pancreas to produce more insulin, which in turn leads to better management of glucose levels in the blood. Findings imply that Tirzepatide peptide may lower hemoglobin A1c (HbA1c) levels in models with Type 2 diabetes by 2.4% after six months of presentation, as suggested by research. The peptide also seems to assist in weight reduction, suggesting a quantity-dependent connection and assisting subjects in one clinical trial to reduce their weight up to 11 kilograms (25 pounds) over six months [i, ii].

Investigations purport that Tirzepatide may not just stimulate insulin release, but there could be other properties. Researchers speculate that the peptide appears to increase the function of pancreatic beta cells, which are the cells responsible for insulin production and release.

Studies also purport that Tirzepatide may make beta cells more efficient at processing insulin, resulting in increased insulin levels in the circulation and less stress on the beta cells. This, in turn, may reduce the rate at which type 2 diabetes worsens.

However, research experiments conducted on research models suggest that Tirzepatide does not elevate insulin levels randomly or unpredictably. It seems this only occurs in reaction to elevated amounts of glucose in the blood. Scientists hypothesize that Tirzepatide may lower insulin levels during fasting periods, which may contribute to an increase in insulin sensitivity over time. Studies suggest that it may also lower fasting glucagon levels, which worsens hyperglycemia by interfering with the glucose metabolism in the liver. In general, these alterations significantly contribute to why the tripeptide is posited to significantly impact glucose and, eventually, HbA1c levels [iii].

Tirzepatide is considered to be a dual agonist, meaning it acts on the glucagon-like peptide-1 receptor and the stomach-inhibitory polypeptide receptor. Research suggests that Tirzepatide peptide seems to have synergistic effects that may make it more successful than stringent GLP-1 agonists considered to manage type 2 diabetes. These synergistic effects appear to be caused by the action at these receptors. Findings imply that the Tirzepatide peptide may have a higher affinity for the GIP receptor compared to its affinity for the GLP-1 receptor.

Interestingly, activation of the GLP-1R receptor seems to enhance the density of beta cells in the pancreas. The activation of the GLP1R increases the expression of the anti-apoptotic bcl-2 gene while, at the same time, a reduction in the expression of the pro-apoptotic Bax and caspase-3 genes takes place. Because of this, the survival rate of beta cells is boosted, which eventually results in higher insulin levels [iv].

Investigations purport that Tirzepatide may have an advantage over other GLP-1R agonists because, in addition to GIPR action, it has also been hypothesized to exhibit GLP-1R activity. Researchers speculate that Tirzepatide may function as GIP does at the GIPR; however, while functioning at the GLP-1R, it appears to prioritize the synthesis of cAMP above the recruitment of -arrestin. There is a difference in activity between exogenous GLP-1 and endogenous GLP-1, and it seems that this difference causes GLP-1R activation without enhancing the physiological internalization of the receptor. These particulars may look obscure to some degree. The final result is increased GLP-1R activity with tarazepide compared to both natural GLP-1 and other synthetic agonists of the GLP-1R receptor [v].

Scientists hypothesize that Tirzepatide appears to affect adiponectin levels, leading to a potential increase in the total amount of the fat-burning peptide. Increased adiponectin levels may inhibit the development of fat cells, leading to a higher energy expenditure rate. This occurs because mitochondria become less efficient. Numerous diseases, including type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver disease, have been linked to having a low amount of this peptide hormone [vi]. Studies suggest that Tirzepatide potentially influences insulin sensitivity in various ways, as increased adiponectin levels increase insulin sensitivity.

References

[i] M. K. Thomas et al., “Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes,” J. Clin. Endocrinol. Metab., vol. 106, no. 2, pp. 388–396, Nov. 2020, doi: 10.1210/clinem/dgaa863.

[ii] T. Min and S. C. Bain, “The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials,” Diabetes Ther., vol. 12, no. 1, pp. 143–157, Jan. 2021, doi: 10.1007/s13300-020-00981-0.

[iii] Frias, Juan Pablo, et al. “Efficacy and Tolerability of Tirzepatide, a Dual Glucose-Dependent Insulinotropic Peptide and Glucagon-like Peptide-1 Receptor Agonist in Patients with Type 2 Diabetes: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Different Dose-Escalation Regimens.” Diabetes, Obesity and Metabolism, vol. 22, no. 6, 11 Feb. 2020, pp. 938–946, 10.1111/dom.13979.

[iv] “Resurrecting the Beta Cell in Type 2 Diabetes,” Medscape. http://www.medscape.org/viewarticle/544820 (accessed Oct. 03, 2023).

[v] F. S. Willard et al., “Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist,” JCI Insight, vol. 5, no. 17, p. e140532, doi: 10.1172/jci.insight.140532.

[vi] M. L. Hartman et al., “Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes,” Diabetes Care, vol. 43, no. 6, pp. 1352–1355, Jun. 2020, doi: 10.2337/dc19-1892.

 

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