经典途径IKKα和IKKβ在胰岛素抵抗和2型糖尿病中的作用机制及药物治疗

摘要

Insulin resistance,obesity and type 2 diabetes mellitus are closely related with the chronic inflammation.Proflammation such as tumor necrosis-α,TNF-α and interleukin-6,IL-6 leads to insulin resistance,obesity and type 2 diabetes mellitus through the activity of canonical IKKα,IKKβ and noncanonical IKKα,IKKβ pathway to activate NF-κB pathway.IKKβ plays a leading role in the canonical IKKα and IKKβ.Inhibiting IKKα and IKKβ can reduce the inflammation significantly,improves insulin sensitivity,decreases body weights and type 2 insulin mellitus.IKKα and IKKβ pathway is a new target for treating insulin,obesity and type 2 diabetes mellitus.%胰岛素抵抗、肥胖病和2型糖尿病与慢性炎症有着密切关系,慢性炎症中促炎症细胞因子如肿瘤坏死因子-α(tumor necrosis-α,TNF-α)、白介素-6(interleukin-6,IL-6)等通过激活经典的IKKα,IKKβ途径和非经典的IKKε,TDK1途径,激活NF-κB途径,引起胰岛素抵抗、肥胖病和2型糖尿病,其中IKKβ在经典的IKKα和IKKβ途径中起着主导作用.阻断IKKα和IKKβ途径,可显著减少炎症、增加胰岛素敏感性,降低体重和减少2型糖尿病.因此,阻断IKKα和IKKβ途径,可作为研究治疗胰岛素抵抗、肥胖病和2型糖尿病的一个新的作用靶点.