脂肪与胰岛素抵抗新概念修改课件.pptxVIP

Products of adipocytes which may be relevant to the pathophysiology of the metabolic syndrome;病因/机理;;AC/IR新概念 AC致m IR AC致L IR AC致心肌IR AC致胰IR AC致内皮IR AC致AC自身IR;TNF-α 妨碍肌、脂Ins信号转导 Glut4表达、转位↓ 肌、脂G摄取↓糖原合成↓ ↑脂解，↑NEFA Adipostat ，TNF-α/leptin,限制AC体积增大 促进细胞调亡，肿瘤恶病质有关 ↑IL-6;IL-6，（来源MP，LC，AC） The most endocrine CK;Resistin(2001) Ch19（人） 仅于WAT特异表达 抗resistin-Ab处理，In-Med-G摄取↑, BG↓ TZD（PPAR-γ配基）下调resistin;肥胖——Resistin——DM2;肥胖——Resistin——DM2;网膜素——又一新发现的脂肪激素 (2003) 313 A.A 作用： 促进AC Ins介导的G运转 ↑ Akt/ PKB 调节能量代谢及胰岛素信号;NEFA-信号分子;Ectopic deposition of lipids NEFA-OX↓→ FFA →Reesterification→non-AC;β、c FA Spillover Lipotoxicity of non-ox metabolic pathway Leptin resistance对 β、c 保护作用↓;β、c FA Spillover Lipotoxicity of non-ox metabolic pathway Leptin resistance对 β、c 保护作用↓;Adiponectin mutation and multimerization;Arg 112 cys Ile 164 Thr;APM 1 3q27 (Acrp 30) (分化AC特异表达) ↑FFA oX ↓BG;APM1 3q27;DGAT2-5Leptin抵抗;通过两条途径;;糖尿病脂代谢异常;肥胖糖尿病 β细胞脂中毒→DM;J.Denis McGarry,PhD;脂代谢异常可能为DM2的主要或原发事件为DM2的基本的病理生理变化;针对糖脂中毒所致IR的治疗;PPARγ/TZD-IR ◎ ↑小Ac, Ins sensitive ◎ ↓大Ac (FFA↓，TNF-α↓） ◎ 抗炎，抗As（抑制α）; TZD Selectively promote adipogenesis in sc and not in visceral sites. Enable the redistribution of body fat away fr the “dangerous”ob sites,towards safer sc ones.;Time (Weeks);Time(Weeks);二甲双胍能改善胰岛素抵抗在大鼠中逆转葡萄糖毒性和脂肪毒性;二甲双胍在体内、外改善脂肪组织的胰岛素敏感性;二甲双胍对人体脂肪组织和游离脂肪酸代谢的影响;Direct and Indirect Cardiovascular Protective Effects of Metformin Ttherapy;MF and FFA;Cellular mechanisms of MF action in the ve SMC and cardiomyocytes;DC 2003, 26, 802