Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
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DOI：
10.1126/scitranslmed.aah4477
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发表时间：
2017-06-14
影响因子：
17.1
通讯作者：
Rosengren, Anders H.
中科院分区：
文献类型：
--
作者：
Axelsson, Annika S.;Tubbs, Emily;Rosengren, Anders H.
一个潜在的有用的药物发现方法是将受疾病影响的组织的基因表达谱（“疾病特征”）与药物特征联系起来，但它是否可以用于识别临床相关的治疗方案仍有待证明。我们分析了共表达网络和遗传数据，以确定肝组织中2型糖尿病的疾病特征。通过查询3800个药物特征库，我们确定了萝卜硫素作为一种化合物，可以逆转疾病的签名。萝卜硫素通过核因子红细胞2相关因子2（NRF 2）的核转位抑制肝细胞葡萄糖的产生，并降低肝细胞生成中关键酶的表达。此外，萝卜硫素逆转了糖尿病动物肝脏中的疾病特征，并以与二甲双胍相似的幅度减弱了过度的葡萄糖产生和葡萄糖耐受不良。最后，萝卜硫素，作为浓缩的西兰花芽提取物，降低了患有失调的2型糖尿病的肥胖患者的空腹血糖和糖化血红蛋白（HbA1c）。
A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes.