Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
Division of Endocrinology, Diabetes and Metabolism Saint Louis University, St. Louis, Missouri.
J Clin Endocrinol Metab. 2018 Mar 1;103(3):1180-1187. doi: 10.1210/jc.2017-02343.
We previously demonstrated the anti-inflammatory and antioxidant effects of exenatide. We now hypothesized that exenatide also increases the plasma concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti-inflammatory protein, and modulates the nuclear factor erythroid 2‒related factor‒Kelchlike ECH-associated protein 1‒antioxidant response element (Nrf-2‒Keap-1‒ARE) system to induce key antioxidant enzymes to suppress inflammatory and oxidative stress.
Twenty-four patients with obesity and type 2 diabetes receiving combined oral and insulin therapy were randomly assigned to receive either exenatide 10 μg or placebo twice a day for 12 weeks.
Exenatide increased IL-1RA concentration by 61% (from 318 ± 53 to 456 ± 88 pg/mL; P < 0.05). Exenatide treatment also suppressed Keap-1 protein (P < 0.05) and increased messenger RNA expression of NQO-1, glutathione S-transferase PI, heme oxygenase-1, and p21 and increased NAD(P)H dehydrogenase [quinone] 1 protein (P < 0.05) in mononuclear cells.
Because IL-1RA protects, maintains, and stimulates β-cell function in humans and Nrf-2‒Keap-1‒ARE protects β cells in animals with experimental diabetes, these actions of exenatide may contribute to a potential protective effect on β cells in diabetes.
我们之前已经证实了 exenatide 的抗炎和抗氧化作用。我们现在假设 exenatide 还可以增加白细胞介素-1 受体拮抗剂 (IL-1RA) 的血浆浓度，IL-1RA 是一种内源性抗炎蛋白，并调节核因子红细胞 2 相关因子- Kelch 样 ECH 相关蛋白 1-抗氧化反应元件 (Nrf-2-Keap-1-ARE) 系统，诱导关键的抗氧化酶来抑制炎症和氧化应激。
24 例接受联合口服和胰岛素治疗的肥胖 2 型糖尿病患者被随机分为两组，分别接受每日两次 exenatide 10 μg 或安慰剂治疗 12 周。
exenatide 使 IL-1RA 浓度增加了 61%（从 318 ± 53 增加到 456 ± 88 pg/mL；P < 0.05）。exenatide 治疗还抑制了 Keap-1 蛋白（P < 0.05），并增加了单核细胞中 NQO-1、谷胱甘肽 S-转移酶 PI、血红素加氧酶-1、p21 和 NAD(P)H 脱氢酶 [醌] 1 蛋白的信使 RNA 表达（P < 0.05）。
因为 IL-1RA 可以保护、维持和刺激人类的β细胞功能，并且 Nrf-2-Keap-1-ARE 可以保护动物实验性糖尿病中的β细胞，所以 exenatide 的这些作用可能有助于对糖尿病中β细胞的潜在保护作用。
