Elucidation of molecular mechanism underlying insulin resistane and inflammation

脯氨酰异构酶 (Pin1) 是一种独特的酶，可识别 pSer/Pro 或 pThr/Pro 基序并改变目标蛋白的构象。我们报道 Pin1 与 Crtc2 结合并抑制肝脏中的 CRE 转录和糖异生活性。此外，Pin1 与主要胰岛素受体底物 IRS-1 结合，增强胰岛素诱导的代谢作用。这些事件最终导致多余的营养物质融入组织。这些发现表明，抑制 Pin1 可能为 NASH 提供一种新的疗法。

Prolyl isomerase (Pin1) is a unique enzyme which recognizes the pSer/Pro or pThr/Pro motif and changes the conformations of target proteins. We reported that Pin1 binds to Crtc2 and suppresses CRE transcriptional and gluconeogenic activity in the liver. In addition, Pin1 associates with IRS-1, a major insulin receptor substrate, and enhances insulin-induced metabolic actions. These events ultimately contribute to the incorporation of excess nutrients into tissues. These findings suggest that inhibition of Pin1 might provide a novel therapy for NASH.