Saxagliptin

Saxagliptin is a highly potent dipeptidyl peptidase-4 (DPP-4) inhibitor that regulates blood glucose by selectively inhibiting the DPP-4 enzyme, thereby elevating levels of endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)^[1-2]. Saxagliptin is used to improve glycemic control in patients with type II diabetes^[3], and has been shown to alleviate inflammation and oxidative stress ^[4].

In vitro, treatment of human papillary thyroid carcinoma cell lines K1 and TPC-1 with Saxagliptin (0.1μM) for 24h significantly enhanced cell migration and invasion capabilities^[5]. Pretreatment of human dental pulp cells with Saxagliptin (500nM–1μM) for 24–48 h, followed by stimulation with LPS (100ng/ml) for 24–48h, significantly suppressed the expression and secretion of pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, while reducing inflammatory responses^[6].

In vivo, oral administration of Saxagliptin (10mg/kg) once daily to a high-fat diet combined with streptozotocin (STZ; 50mg/kg)-induced type 2 diabetic C57BL/6J mouse model significantly improved β-cell mass and islet morphology, regardless of whether intervention began 7 days before or 1 day after STZ injury^[7]. In another study, daily oral administration of Saxagliptin (10mg/kg) for 35 days to STZ (60mg/kg/day)-induced diabetic C57BL/6J mice markedly attenuated diabetes-induced somatic chromosomal instability. Saxagliptin significantly reduced the frequency of micronucleus formation in bone marrow and reversed diabetes-induced suppression of bone marrow nucleated cell proliferation^[8].

References:
[1] Thareja S, Aggarwal S, Malla P, et al. Saxagliptin: a new drug for the treatment of type 2 diabetes. Mini Rev Med Chem. 2010 Jul;10(8):759-65.
[2] Kania DS, Gonzalvo JD, Weber ZA. Saxagliptin: a clinical review in the treatment of type 2 diabetes mellitus. Clin Ther. 2011 Aug;33(8):1005-22.
[3] Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26.
[4] Zhang L, Qi X, Zhang G, et al. Saxagliptin protects against hypoxia-induced damage in H9c2 cells. Chem Biol Interact. 2020 Jan 5;315:108864.
[5] He L, Zhang T, Sun W, et al. The DPP-IV inhibitor saxagliptin promotes the migration and invasion of papillary thyroid carcinoma cells via the NRF2/HO1 pathway. Med Oncol. 2020 Oct 1;37(11):97.
[6] Guo X, Chen J. The protective effects of saxagliptin against lipopolysaccharide (LPS)-induced inflammation and damage in human dental pulp cells. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1288-1294.
[7] Poucher SM, Cheetham S, Francis J, et al. Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic β-cell mass in a streptozotocin-induced mouse model of type 2 diabetes. Diabetes Obes Metab. 2012 Oct;14(10):918-26.
[8] Attia SM, Ahmad SF, Nadeem A, et al. Saxagliptin, a selective dipeptidyl peptidase-4 inhibitor, alleviates somatic cell aneugenicity and clastogenicity in diabetic mice. Mutat Res Genet Toxicol Environ Mutagen. 2023 Nov-Dec;892:503707.

Saxagliptin是一种高效二肽基肽酶-4（DPP-4）抑制剂，通过选择性抑制DPP-4酶，从而升高内源性胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素释放多肽（GIP）的水平以调节血糖^[1-2]。Saxagliptin可用于改善II型糖尿病患者对葡萄糖的敏感性^[3]。Saxagliptin可减轻炎症与氧化应激反应^[4]。

在体外，Saxagliptin（0.1μM）处理人乳头状甲状腺癌细胞系K1和TPC-1细胞24h。Saxagliptin显著增强细胞的迁移和侵袭能力^[5]。Saxagliptin（500nM–1μM）预处理人牙髓细胞24–48h，随后以LPS（100ng/ml）刺激24–48h，能够显著抑制促炎因子TNF-α、IL-1β和IL-8的表达与分泌，同时降低炎症反应^[6]。

在体内，Saxagliptin（10mg/kg）每日一次口服给药，用于处理高脂饮食联合链脲佐菌素（STZ；50mg/kg）诱导的2型糖尿病C57BL/6J小鼠模型，无论从STZ损伤前7天或损伤后1天开始干预，均能显著改善β细胞质量和胰岛形态^[7]。Saxagliptin（10mg/kg）每日一次口服给药，用于处理链脲佐菌素（STZ；60mg/kg/天）诱导的糖尿病C57BL/6J小鼠，持续35天。Saxagliptin显著减轻了糖尿病引起的体细胞染色体不稳定性。Saxagliptin显著降低了糖尿病小鼠骨髓微核形成频率，并逆转了糖尿病导致的骨髓有核细胞增殖抑制^[8]。