文档介绍：脂中毒与胰岛素抵抗新概念脂中毒与胰岛素抵抗新概念李李秀秀钧钧华西医科大学附一院华西医科大学附一院内分泌科内分泌科 Products of Products of adipocytes adipocytes which may be relevant to which may be relevant to the the pathophysiology pathophysiology of the metabolic syndrome of the metabolic syndrome 脂肪组织脂肪组织————新的内分泌器官新的内分泌器官 Resistin Resistin (2001) (2001) Adiponectin Adiponectin (1991) (1991) Vitronectin Vitronectin (2000) (2000) PPARs Omentin Omentin (2003) (2003) 病因病因/ /机理机理遗传因素遗传因素环境因素环境因素 AC AC肥大肥大/ /增殖增殖 Adipocytokines Adipocytokines TNF- TNF- α↑α↑ NEFA NEFA ↑↑IL- IL- 6 6↑↑Resistin Resistin ↑↑ PAI-1 PAI-1 ↑↑ AP AP ↓↓ VF VF ( ( omental omental F) F) ↓↓ apM apM 1 1 Omentin Omentin MS MS IR IGT 高血压血脂异常 DC, 2003, 26: 2442 AC/IR AC/IR 新概念新概念 AC AC致致m IR m IR AC AC 致致L L IR IR AC AC 致心肌致心肌 IR IR AC AC 致胰致胰 IR IR AC AC 致内皮致内皮 IR IR AC AC 致致AC AC自身自身 IR IR TNF- TNF- αα妨碍肌、脂妨碍肌、脂 Ins Ins 信号转导信号转导 Glut4 Glut4 表达、转位表达、转位↓↓肌、脂肌、脂 G G摄取摄取↓↓糖原合成糖原合成↓↓↑↑脂解, 脂解, ↑↑NEFA NEFA Adipostat Adipostat , ,TNF- TNF- αα/ /leptin leptin , ,限制限制 AC AC体体积增大积增大促进细胞调亡,肿瘤恶病质有关促进细胞调亡,肿瘤恶病质有关↑↑IL-6 IL-6 IL-6 IL-6 ,( ,( 来源来源 MP MP, ,LC LC, ,AC AC) ) The most endocrine CK The most endocrine CK TNF- α↑↑CRP CRP OB-low grade inflammatory state OB-low grade inflammatory state →→As As HPA AXIS HPA AXIS ↑↑ AC AC IL-6 IL-6 ↑↑( (一) 一) F F 脂肝、脂脑对话脂肝、脂脑对话↑↑肝肝TG TG ↑↑脂解脂解 OP OPE E 2 2( (——) ) ( (——) ) Resistin Resistin (2001) (2001) Ch Ch 19 19( (人) 人) 仅于仅于 WAT WAT 特异表达特异表达抗抗resistin resistin - -Ab Ab处理, 处理, In-Med-G In-Med-G 摄取摄取↑↑, ,BG BG↓↓ TZD TZD ( (PPAR- PPAR- γγ配基)下调配基)下调 resistin resistin 肥胖肥胖———— Resistin Resistin ———— DM2 DM2 SI SI↓↓ IGT IGT DM2 DM2 肥胖肥胖———— Resistin Resistin ———— DM2 DM2 SI SI↓↓ IGT IGT DM2 DM2 PPAR- PPAR- γγ TZD TZD Link btw ob&DM2 Link btw ob&DM2