Division of Endocrinology, Diabetes, and Metabolism, State University of New York at Buffalo, Buffalo, New York 14209, USA.
J Clin Endocrinol Metab. 2012 Jan;97(1):198-207. doi: 10.1210/jc.2011-1508. Epub 2011 Oct 19.
Our objective was to determine whether exenatide exerts an antiinflammatory effect.
Twenty-four patients were prospectively randomized to be injected sc with either exenatide 10 μg twice daily [n = 12; mean age = 56 ± 3 yr; mean body mass index = 39.8 ± 2 kg/m(2); mean glycosylated hemoglobin (HbA1c) = 8.6 ± 0.4%] or placebo twice daily (n = 12; mean age = 54 ± 4 yr; mean body mass index = 39.1 ± 1.6 kg/m(2); mean HbA1c = 8.5 ± 0.3%) for 12 wk. Fasting blood samples were obtained at 0, 3, 6, and 12 wk. Blood samples were also collected for up to 6 h after a single dose of exenatide (5 μg) or placebo.
Fasting blood glucose fell from 139 ± 17 to 110 ± 9 mg/dl, HbA1c from 8.6 ± 0.4 to 7.4 ± 0.5% (P < 0.05), and free fatty acids by 21 ± 5% from baseline (P < 0.05) with exenatide. There was no weight loss. There was a significant reduction in reactive oxygen species generation and nuclear factor-κB binding by 22 ± 9 and 26 ± 7%, respectively, and the mRNA expression of TNFα, IL-1β, JNK-1, TLR-2, TLR-4, and SOCS-3 in mononuclear cells by 31 ± 12, 22 ± 10, 20 ± 11, 22 ± 9, 16 ± 7, and 31 ± 10%, respectively (P < 0.05 for all) after 12 wk of exenatide. After a single injection of exenatide, there was a reduction by 20 ± 7% in free fatty acids, 19 ± 7% in reactive oxygen species generation, 39 ± 11% in nuclear factor-κB binding, 18 ± 9% in TNFα expression, 26 ± 7% in IL-1β expression, 18 ± 7% in JNK-1 expression, 24 ± 12% in TLR-4 expression, and 23 ± 11% in SOCS-3 expression (P < 0.05 for all). The plasma concentrations of monocyte chemoattractant protein-1, matrix metalloproteinase-9, serum amyloid A, and IL-6 were suppressed after 12 wk exenatide treatment by 15 ± 7, 20 ± 11, 16 ± 7, and 22 ± 12%, respectively (P < 0.05 for all).
Exenatide exerts a rapid antiinflammatory effect at the cellular and molecular level. This may contribute to a potentially beneficial antiatherogenic effect. This effect was independent of weight loss.
我们的目的是确定 exenatide 是否具有抗炎作用。
24 名患者前瞻性随机分为两组，分别每日皮下注射 exenatide 10μg（n=12；平均年龄=56±3 岁；平均体重指数=39.8±2kg/m²；平均糖化血红蛋白（HbA1c）=8.6±0.4%）或安慰剂（n=12；平均年龄=54±4 岁；平均体重指数=39.1±1.6kg/m²；平均 HbA1c=8.5±0.3%），持续 12 周。在 0、3、6 和 12 周时采集空腹血样。单次给予 exenatide（5μg）或安慰剂后也采集了长达 6 小时的血液样本。
空腹血糖从 139±17mg/dl 降至 110±9mg/dl（P＜0.05），HbA1c 从 8.6±0.4%降至 7.4±0.5%（P＜0.05），游离脂肪酸降低 21±5%（P＜0.05）。无体重减轻。单核细胞中的活性氧（ROS）生成和核因子-κB 结合分别减少 22±9%和 26±7%（P＜0.05），TNFα、IL-1β、JNK-1、TLR-2、TLR-4 和 SOCS-3 的 mRNA 表达分别减少 31±12%、22±10%、20±11%、22±9%、16±7%和 31±10%（P＜0.05）。exenatide 单次注射后，游离脂肪酸减少 20±7%，ROS 生成减少 19±7%，核因子-κB 结合减少 39±11%，TNFα 表达减少 18±9%，IL-1β 表达减少 26±7%，JNK-1 表达减少 18±7%，TLR-4 表达减少 24±12%，SOCS-3 表达减少 23±11%（P＜0.05）。经过 12 周的 exenatide 治疗，单核细胞趋化蛋白-1、基质金属蛋白酶-9、血清淀粉样蛋白 A 和 IL-6 的血浆浓度分别降低了 15±7%、20±11%、16±7%和 22±12%（P＜0.05）。
exenatide 在细胞和分子水平上迅速发挥抗炎作用。这可能有助于发挥潜在的有益的抗动脉粥样硬化作用。这种作用与体重减轻无关。
