综述PKR与胰岛素抵抗

胰岛素抵抗是2型糖尿病重要的发病机制之一。脂类、氧化应激及炎症因子等的刺激会导致胰岛素受体底物IRS的丝氨酸磷酸化,阻碍正常的酪氨酸磷酸化从而导致胰岛素与其受体结合并激活下游底物的P13K能力下降,减弱了胰岛素信号转导,引起胰岛素抵抗。越来越多研究表明,PKR(double-stranded RNA-dependent protein kinase)在肥胖状态及脂类、炎症因子刺激下能够被激活,活化的PKR能通过激活IKKβ和JNK使IRS1的丝氨酸磷酸化升高,使IRS1的酪氨酸磷酸化减少从而阻碍了胰岛素的PI3K途径从而引起胰岛素抵抗。本文综述了最新研究结果,阐明了PKR在胰岛素抵抗中发挥的重要作用。

Insulin resistance is a crucial component in the development of type2 diabetes. Lipids, oxidative stress and inflammatory cytokine have been suggested to induce phosphorylation of serine on insulin receptor substrate IRS which blocks the formal phosphorylation of tyrosine and then affects the combination of insulin with IRS , attenuates the capacity of activating downstream signal molecule P13K and disorders insulin- mediated signal transduction, thus leading to insulin resistance. More and more evidence reveal that double-stranded RNA-dependent protein kinase PKR can be activated in the presence of lipids and inflammatory cytokines or on condition of obesity. Activated PKR would enhance the phosphorylation of serine on IRS with decline in tyrosine phosphorylation through IKKβ and JNK and impede the PI3K pathway evoked by insulin, which would trigger insulin resistance as a final consequence. In summary, this paper is aimed to elucidate the role of PKR in insulin resistance on the basis of recent studies.