Tirzepatide Peptide And Weight-Related Studies
Results from experimental studies purport that Tirzepatide may improve glycemic control by enhancing β-cell activity, insulin sensitivity, and α-cell action.
Studies suggest Tirzepatide may offer a unique combination of GIP sequence modification and GLP-1 receptor agonist action. The goal in developing Tirzepatide was to bind to the GLP-1 receptor around five times weaker than natural GLP-1 while also achieving an affinity for the GIP receptor that was on par with native GIP. The chemical is a 39-amino-acid linear peptide with a C20 fatty acid component.
In animal studies, Tirzepatide has been hypothesized to act as a biased agonist at the GLP-1 receptor, causing it to signal the production of cyclic adenosine monophosphate (cAMP). However, research suggests it may cause less GLP-1 receptor internalization due to decreased recruitment of β-arrestin. Based on the results of these studies, this process seems to allow Tirzepatide to signal at the GLP-1 receptor for an extended period, which might increase the insulinotropic action on pancreatic beta cells. But biased agonism's ramifications are still up in the air.
Results from experimental studies purport that Tirzepatide may improve glycemic control by enhancing β-cell activity, insulin sensitivity, and α-cell action. Tirzepatide appeared to considerably enhance insulin sensitivity, total insulin secretion, and insulin action's first and second phases. While testing meal tolerance, Tirzepatide seemed to decrease both fasting and meal-stimulated glucagon secretion. Results from mouse experiments indicate that Tirzepatide may improve insulin resistance in a weight-dependent and independent manner. Investigations purported that Tirezepatide may improve insulin sensitivity more than a selective GLP-1 receptor agonist per weight loss unit, with this effect being most noticeable in research models of greater weight loss. Weight loss may only partially account for improvement in insulin sensitivity.
Tirzepatide, Diabetes, And Obesity
Several pathophysiological features, such as insulin resistance, impaired insulin secretion, obesity, reduced incretin effect, increased glucagon production, dyslipidemia, and so on, define type 2 diabetes. Type 2 diabetes, therefore, is about more than just hyperglycemia.
When it comes to the pathophysiology of conditions like type 2 diabetes, insulin resistance, hypertension, dyslipidemia, and non-alcoholic fatty liver disease, obesity is by far the most important component. Reduced body fat may improve insulin sensitivity, glycaemic management, and comorbidities because of the interconnected pathophysiology of these conditions. The metabolic anomalies of type 2 diabetes may be reversed with greater weight reduction, which may improve glycemia and lead to diabetic remission. Studies examining various intervention types with different designs and locations have reported the potential for weight loss to induce remission of type 2 diabetes.
The capacity to maintain non-diabetes glycemia without glucose-lowering therapy was the overall criterion for remission, but the precise criteria varied among different investigations. The positive benefits of greater weight reduction on glycemia further underscore the significance of weight management for research models of type 2 diabetes. Cardiovascular risk factors, such as blood pressure and cholesterol, may be improved with a modest weight reduction of at least 5%, and non-alcoholic fatty liver disease may be improved with a weight loss of ≥7%.
In response to caloric intake, the digestive tract appears to secrete two incretin hormones—glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—that operate to regulate blood sugar levels. Research models of type 2 diabetes are considered to have a reduced ability to do this, although methods that decrease glucose levels may possibly restore it partially. By delaying stomach emptying, increasing glucose-stimulated insulin secretion, decreasing food intake, inhibiting glucagon release in hyperglycemic or euglycemic states, and improving glycemic control, GLP-1 receptor agonists have been hypothesized to help research models of type 2 diabetes lose weight.
GIP, unlike GLP-1, has been theorized to promote glucagon secretion in hypoglycemic situations; however, it has been speculated to have a reduced impact on glucose-stimulated insulin secretion in type 2 diabetic research subjects. Because the dipeptidyl peptidase-4 enzyme breaks them down quickly, these two incretin hormones are considered to display a half-life of just a few minutes at their receptors in normal physiology. The peptide is also being studied for its potential on obesity, non-cirrhotic non-alcoholic steatohepatitis (NASH), major adverse cardiovascular events (MACE), and heart failure with preserved ejection fraction.
Scientists interested in more Tirzepatide studies may visit the Biotech Peptides website for more educational papers. Please note that none of the substances mentioned in this article have been approved for human or animal consumption and should not be used by unlicensed professionals. Any bodily introduction is strictly prohibited by law, and these research compounds should only be used in contained environments such as secure laboratories. This article is delivered for educational purposes only.
References
[i] De Block, Christophe, et al. “Tirzepatide for the Treatment of Adults with Type 2 Diabetes: An Endocrine Perspective.” Diabetes, Obesity and Metabolism, 5 Aug. 2022, https://doi.org/10.1111/dom.14831.
[ii] Chavda VP, Ajabiya J, Teli D, Bojarska J, Apostolopoulos V. Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review. Molecules. 2022 Jul 5;27(13):4315. doi: 10.3390/molecules27134315. PMID: 35807558; PMCID: PMC9268041.
[iii] Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. . Epub 2022 Jun 4. PMID: 35658024.
[iv] Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021 Jul 10;398(10295):143-155. doi: 10.1016/S0140-6736(21)01324-6. Epub 2021 Jun 27. Erratum in: Lancet. 2021 Jul 17;398(10296):212. PMID: 34186022.
[v] Forzano I, Varzideh F, Avvisato R, Jankauskas SS, Mone P, Santulli G. Tirzepatide: A Systematic Update. Int J Mol Sci. 2022 Nov 23;23(23):14631. doi: 10.3390/ijms232314631. PMID: 36498958; PMCID: PMC9741068.
[vi] Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545. PMID: 35133415; PMCID: PMC8826179.
[vii] Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24. PMID: 35210595; PMCID: PMC8938269.
[viii] Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ, Holst JJ, D'Alessio DA, Coghlan MP, Rosenkilde MM, Campbell JE, Sloop KW. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020 Sep 3;5(17):e140532. doi: 10.1172/jci.insight.140532. PMID: 32730231; PMCID: PMC7526454.
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