Tirzepatide 5mg

Tirzepatide 5mg  belongs to a class of compounds known as dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. These molecules target multiple pathways in the body that regulate glucose and energy metabolism.

Numerous preclinical and in vitro studies have been conducted to assess the potential mechanisms of action, efficacy, and safety of tirzepatide. Some key findings from these studies are as follows:

In vitro studies have revealed that tirzepatide binds to both GIP and GLP-1 receptors on cells involved in glucose regulation, such as pancreatic beta cells and adipocytes. This dual activation of receptors leads to enhanced insulin secretion and improved glucose uptake by cells. This mechanism aims to address multiple facets of diabetes and obesity pathology.¹

Fat cell GIP receptors have been demonstrated across various models, including animals and cell cultures using both gene expression analysis and functional assays.^2,3 These studies have revealed that GIP contributes to enhanced glucose uptake and the activation of lipoprotein lipase and lipogenesis, which involves the conversion of free fatty acids into triglycerides within isolated fat cells in vitro.^4,5 Furthermore, GIP has been found to facilitate the process of de novo lipogenesis from glucose and it plays a role in lipolysis, as evidenced by in vitro investigations.^2,6 Importantly, the implications of these findings extend to adipose tissue lipid storage. Animal studies have demonstrated that when adipose tissue glucose-dependent insulinotropic polypeptide receptor (GIPR) is selectively deleted, the resulting reduction in GIPR function leads to a decrease in high-fat diet-induced obesity.⁷

GLP-1 receptors have been detected within the testis.⁸ Moreover, investigations have demonstrated that these GLP-1 receptors play a beneficial role in mitigating testicular inflammation and enhancing sperm quality, particularly in the context of obesity, as observed in mouse studies.⁹ In addition to this, in diabetic rats, tirzepatide demonstrated the ability to ameliorate impairments in spatial learning and memory by effectively modulating aberrant insulin resistance and inflammatory responses.⁹

Another animal study showed the potential of tirzepatide in the management of obesity-related cancers, as evidenced by its ability to significantly reduce tumor growth rates in the murine MC38 colon cancer model while also addressing critical factors such as food intake, insulin, and leptin levels.¹⁰

References: 1. Willard FS, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020 Sep 3;5(17):e140532. 2. Hauner H, Glatting G, Kaminska D, Pfeiffer EF. Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes. Ann Nutr Metab. 1988;32(5-6):282-8. 3. Yip RG, Boylan MO, Kieffer TJ, Wolfe MM. Functional GIP receptors are present on adipocytes. Endocrinology. 1998 Sep;139(9):4004-7. 4. Eckel RH, Fujimoto WY, Brunzell JD. Gastric inhibitory polypeptide enhanced lipoprotein lipase activity in cultured preadipocytes. Diabetes. 1979 Dec;28(12):1141-2. 5. Song DH, et al. Glucose-dependent insulinotropic polypeptide enhances adipocyte development and glucose uptake in part through Akt activation. Gastroenterology. 2007 Dec;133(6):1796-805. 6. Kim SJ, Nian C, McIntosh CH. GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. J Lipid Res. 2010 Nov;51(11):3145-57. 7. Ugleholdt R, et al. Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain. J Biol Chem. 2011 Dec 30;286(52):44632-45. 8.Caltabiano R, et al. Glucagon-like peptide-1 receptor is expressed in human and rodent testis. Andrology. 2020 Nov;8(6):1935-1945. 9. Guo X, et al. Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats. Front. Pharmacol. Sec. Neuropharmacology Volume 14 - 2023. 10. Huang L, Zeng J, Wang Y, Pollak M. Tirzepatide inhibits tumor growth in mice with diet-induced obesity. Downloaded from: https://www.biorxiv.org/content/10.1101/2023.06.22.546093v1.full