Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.
Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.
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胰岛素增敏剂可预防和改善实验性 1 型糖尿病。
DOI：
10.1152/ajpendo.00329.2016
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Bar-Tana,Jacob
中科院分区：
文献类型：
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作者：
Valitsky,Michael;Hoffman,Amnon;Unterman,Terry;Bar-Tana,Jacob
胰岛素依赖型1型糖尿病(T1D)是由自身免疫β细胞衰竭引起的，而全身性胰岛素抵抗被认为是胰岛素非依赖型2型糖尿病(T2D)的标志。与这种典型的二分法相反，胰岛素抵抗似乎先于T1D的显性糖尿病阶段并预测其进展，这意味着胰岛素增敏剂可能改变T1D的病程。然而，以前通过胰岛素增敏剂改善动物模型或患者的T1D的尝试基本上失败了。在T2D动物模型中，甲基取代长链二酸类似物(MEDICA)对胰岛素的增敏作用超过了现有的胰岛素增敏剂，从而激发了我们在T1D背景下探索MEDICA的兴趣。在链脲佐菌素(STZ)糖尿病大鼠和自身免疫性非肥胖糖尿病(NOD)小鼠身上验证了中药对T1D病程的调节作用。当加入亚治疗胰岛素时，Medica治疗可使STZ糖尿病大鼠的显性糖尿病恢复正常，并预防/推迟NOD小鼠的自身免疫T1D。梅地亚疗法不能改善β细胞的胰岛素含量或胰岛素炎症评分，但其疗效是通过明显的全身胰岛素敏感度来解释的。综上所述，有效的胰岛素增敏剂可以抵消自身免疫性T1D的遗传易感性，并将亚治疗性胰岛素放大为治疗显性T1D的有效治疗措施。
Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D.