Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, is a prospective therapy for type 2 diabetes mellitus (T2DM) [1-3].
Tizepatide(0.2 µM;7days) can ameliorate high glucose-induced neurodegeneration and overcome neuronal insulin resistance[4].
Tirzepatide (10 nmol/kg;14days; s.c) remarkably reduces LPS-mediated inflammatory responses by inhibiting the cardiac protein levels of TNF-α, IL-6, and IL-1B in mice[5]. Tirzepatide(3-10 nmol/kg;14days; s.c) enhances insulin sensitivity in obese mice[6]. Tirzepatide had anti-allergic inflammatory effects for the aeroallergen-induced model in obese asthma[7]. Tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes[8].
References:
[1]. Willard FS, Douros JD, et,al. 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.
[2]. Coskun T, Sloop KW, et,al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. PMID: 30473097; PMCID: PMC6308032.
[3]. Forzano I, Varzideh F, et,al. Tirzepatide: A Systematic Update. Int J Mol Sci. 2022 Nov 23;23(23):14631. doi: 10.3390/ijms232314631. PMID: 36498958; PMCID: PMC9741068.
[4]. Fontanella RA, Ghosh P, et, al. Tirzepatide prevents neurodegeneration through multiple molecular pathways. J Transl Med. 2024 Jan 29;22(1):114. doi: 10.1186/s12967-024-04927-z. PMID: 38287296; PMCID: PMC10823712.
[5]. Liu Q, Zhu J, et,al. Tirzepatide attenuates lipopolysaccharide-induced left ventricular remodeling and dysfunction by inhibiting the TLR4/NF-kB/NLRP3 pathway. Int Immunopharmacol. 2023 Jul;120:110311. doi: 10.1016/j.intimp.2023.110311. Epub 2023 May 15. PMID: 37196559.
[6]. Samms RJ, Christe ME, et,al. GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice. J Clin Invest. 2021 Jun 15;131(12):e146353. doi: 10.1172/JCI146353. PMID: 34003802; PMCID: PMC8203452.
[7]. Toki S, Zhang J, et,al. Dual GIPR and GLP-1R agonist tirzepatide inhibits aeroallergen-induced allergic airway inflammation in mouse model of obese asthma. Clin Exp Allergy. 2023 Feb;53(2):216-221. doi: 10.1111/cea.14252. Epub 2022 Nov 15. PMID: 36377605; PMCID: PMC10163938.
[8]. Thomas MK, Nikooienejad A, 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. 2021 Jan 23;106(2):388-396. doi: 10.1210/clinem/dgaa863. PMID: 33236115; PMCID: PMC7823251.
Tirzepatide是一种双重胰高血糖素样肽-1 (GLP-1)和葡萄糖依赖性胰岛素性多肽(GIP)受体激动剂,是2型糖尿病(T2DM)的前瞻性治疗药物[1-3]。
Tirzepatide (0.2 µM;7d)可改善高糖诱导的神经变性,克服神经元胰岛素抵抗[4]。
Tirzepatide(10 nmol/kg;14days; s.c)通过抑制小鼠心肌蛋白TNF-α、IL-6和IL-1B水平显著降低LPS介导的炎症反应[5]。Tirzepatide(3-10 nmol/kg;14days; s.c)慢性治疗可增强肥胖小鼠的胰岛素耐量[6]。Tirzepatide对空气变应原诱导的肥胖哮喘模型具有抗变应性炎症作用[7]。Tirzepatide改善2型糖尿病的β细胞功能和胰岛素敏感性[8]。