Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes.
Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes.
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DOI：
10.1186/1476-9255-9-35
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Herbst K
中科院分区：
文献类型：
--
作者：
Frankwich K;Tibble C;Torres-Gonzalez M;Bonner M;Lefkowitz R;Tyndall M;Schmid-Schönbein GW;Villarreal F;Heller M;Herbst K
肥胖是一种导致胰岛素受体功能丧失和胰岛素敏感性降低的亚临床炎症状态。在啮齿类动物模型中，抑制炎症酶基质金属蛋白酶（MMPs） 6个月可恢复胰岛素受体功能和胰岛素敏感性。这项为期12周的双盲、随机、安慰剂（PL）对照的概念验证研究是为了确定MMP抑制剂（MMPI）、强力霉素是否能降低肥胖2型糖尿病（DM2）患者的炎症总体标志物并增强肌肉胰岛素敏感性。该研究包括非DM2对照组（n = 15）和随机分配到PL （n = 13）或强力霉素100mg每日两次（MMPI; n = 11）的DM2受试者。在第1天对所有参与者进行评估；治疗84 d后对MMPI和PL组进行评价。MMPI组炎症标志物c反应蛋白（P < 0.05）和髓过氧化物酶（P = 0.01）显著降低，而PL组无显著降低。MMPI还显著增加了骨骼肌活化/总胰岛素信号介质：3′磷酸肌苷激酶-1 (PDK1) （p < 0.03）、蛋白激酶B (PKB/Akt) （p < 0.004）和糖原合成酶激酶3ß （GSK3ß） （p < 0.03）。该研究表明，短期治疗伴有MMPI的糖尿病患者可减少炎症并改善胰岛素敏感性。更大规模、更长期的研究是有必要的，以确定强力霉素是否可以改善糖尿病患者的血糖控制。Clinicaltrials.gov NCT01375491
Obesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs), for 6 months in rodent models restores insulin receptor function and insulin sensitivity. This 12-week double-blind, randomized, placebo (PL)-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI), doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2). The study included non-DM2 controls (n = 15), and DM2 subjects randomized to PL (n = 13) or doxycycline 100 mg twice daily (MMPI; n = 11). All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment. There was a significant decrease in inflammatory markers C-reactive protein (P < 0.05) and myeloperoxidase (P = 0.01) in the MMPI but not PL group. The MMPI also significantly increased skeletal muscle activated/total insulin signaling mediators: 3’phosphoinositide kinase-1 (PDK1) (p < 0.03), protein kinase B (PKB/Akt) (p < 0.004), and glycogen synthase kinase 3ß (GSK3ß) (p < 0.03). This study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes. Clinicaltrials.gov NCT01375491
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影响因子：
4.3
作者：
Hackmann, Amy E.;Rubin, Brian G.;Sanchez, Luis A.;Geraghty, Patrick A.;Thompson, Robert W.;Curci, John A.
通讯作者：
Curci, John A.
DOI：
10.1161/01.atv.0000121571.78696.dc
发表时间：
2004-04-01
影响因子：
8.7
作者：
Brown, DL;Desai, KK;Golub, LM
通讯作者：
Golub, LM
影响因子：
16.2
作者：
Nagaretani, H;Nishizawa, H;Takahashi, M
通讯作者：
Takahashi, M
影响因子：
20.1
作者：
Chung, Ada W. Y.;Yang, H. H. Clarice;van Breemen, Cornelis
通讯作者：
van Breemen, Cornelis
影响因子：
5.3
作者：
Dominguez-Rodriguez, Alberto;Abreu-Gonzalez, Pedro;Kaski, Juan Carlos
通讯作者：
Kaski, Juan Carlos