Sci Transl Med ：针对2型糖尿病的新型个体化疗法

  近日，来自瑞典隆德大学的研究人员检测了一种针对2型糖尿病的新型疗法，该疗法仅仅靶向作用于疾病本身，而并非患者的机体症状；而研究者也首次利用了单一病人的遗传风险预测，该新型疗法可以完全恢复患者机体产生胰岛素的能力，相关研究发表于国际杂志Science Translational Medicine上。
  研究者Anders Rosengren教授表示，针对单一个体风险预测的个体化疗法潜力非常广大，我们的研究为有效阻断2型糖尿病的风险基因带来了极大的帮助；早在2009年，科学家们就在Science上发表了一项关于糖尿病的里程碑研究，研究人员报道了机体的一种常见基因突变可以使得产胰岛素细胞对应激激素敏感，而这种突变损伤了细胞分泌胰岛素的能力，从而引发糖尿病的发生。
  在随后的研究工作中，研究人员开发了一种名为Yohimbin的新型药物，在实验条件下其可以有效阻断基因突变对机体胰岛素产生细胞的损伤效应。研究者表示，这种基因突变非常常见，30%的人类机体均存在这种突变，其甚至在2型糖尿病患者机体也很频繁，瑞典有40万人都患有2型糖尿病，其中40%患者都是该基因突变的携带者。
  这项研究中，研究人员招募了50名2型糖尿病患者进行研究，其中21名患者没有携带风险基因突变，其余个体均携带该突变；研究中所有个体均进行了葡萄糖耐受性测试，该测试可以揭示患者机体应对过度糖类负担时胰岛素的分泌情况，结果显示，胰岛素的分泌情况在25%的携带风险突变基因的患者中表现非常糟糕。
  Erik Renstrom博士说道，风险基因携带者可以获得和无风险基因患者同样的分泌胰岛素的能力。Yohimbin可以中和风险基因对患者机体的效应，Yohimbin必须被修饰才可以使得副作用降到最低，当前研究人员需要一些合作者才可以完成将这种新型药物副作用降低的目的，一旦修饰成功，该药物或将可以有效治疗40%的携带风险突变的2型糖尿病患者。（转化医学网360zhyx.com）

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Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist
Sci Transl Med DOI: 10.1126/scitranslmed.3009934
Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist
The feasibility of exploiting genomic information for individualized treatment of polygenic diseases remains uncertain. A genetic variant in ADRA2A, which encodes the α2A-adrenergic receptor (α2AAR), was recently associated with type 2 diabetes. This variant causes receptor overexpression and impaired insulin secretion; thus, we hypothesized that blocking α2AAR pharmacologically could improve insulin secretion in patients with the risk genotype. A total of 50 type 2 diabetes patients were recruited on the basis of ADRA2A genotype for a randomized placebo-controlled intervention study with the α2AAR antagonist yohimbine. The patients received 0, 10, or 20 mg of yohimbine at three separate visits. The primary endpoint was insulin secretion at 30 min (Ins30) during an oral glucose tolerance test (OGTT). Patients with the risk variant had 25% lower Ins30 than those without risk genotype. After administration of 20 mg of yohimbine, Ins30 was enhanced by 29% in the risk group, making secretion similar to patients carrying the low-risk allele. The corrected insulin response and disposition index in individuals with the high-risk (but not low-risk) allele were improved by 59 ± 18% and 43 ± 14%, respectively. The beneficial effect of yohimbine was not a consequence of improved insulin sensitivity. In summary, the data show that the insulin secretion defect in patients carrying the ADRA2A risk genotype can be corrected by α2AAR antagonism. The findings show that knowledge of genetic risk variants can be used to guide therapeutic interventions that directly target the underlying pathophysiology and demonstrate the potential of individualized genotype-specific treatment of type 2 diabetes.