胰岛素抵抗与多囊卵巢综合征PPT.ppt

胰岛素抵抗与多囊卵巢综合征;1921年，Achard 和 Their首先发现糖代谢异常与高雄激素血症有关; 1935年， Stein and Leventhal首先提出PCOS; 1976年，Kahn 和同事发现高雄激素血症、胰岛素抵抗和黑棘皮症有关; 1980年，Burghen 首先提出PCOS与高雄激素血症、高胰岛素血症有关;;Figure 2. Section of a polycystic ovary with multiple subscapular follicular cysts and stromal hypertrophy (left panel). At higher power (x100) islands of luteinized theca cells are visible in the stroma (right panel). This morphological change is called stromal hyperthecosis and appears to be directly correlated with circulating insulin levels. ;一、胰岛素与卵巢功能的关系;胰岛素通过IGF-1受体刺激卵巢分泌雌激素，雄激素及 孕酮(细胞色素 p-450c 17α 17 α-羟化酶 ) 胰岛素抑制肝脏分泌SHBG 雄激素的效应 胰岛素抑制肝脏合成 IGFBP-1 IGF-1的效应 同 Gn相互作用 抑制卵泡的凋亡 闭锁 上调 IGF-1受体;胰岛素及其受体的结构;胰岛素的作用机理（1）;FIG 1. The IR is a heterotetramer consisting of two a, b-dimers linked by disulfide bonds. The a-subunit contains the ligand-binding site, and the b-subunit contains a ligand-activated tyrosine kinase. Tyrosine autophosphorylation increases the receptor’ s tyrosine kinase activity whereas serine phosphorylation inhibits it.;胰岛素抵抗的机理(1);Figure 9. The tyrosine-phosphorylated IR phosphorylates intracellular substrates, such as IR substrate (IRS)-1 and IRS-2, initiating signal transduction and the plieotropic actions of insulin. The activation of PI3-K (PI3-kinase) by tyrosine-phosphorylated IRS-1 appears to be the pathway for insulin-mediated glucose transport. The Ras-MAP kinase pathway appears to regulate cell growth and glycogen synthesis. ;IR 丝氨酸磷酸化因子 IR 酪氨酸激酶抑制因子 膜糖蛋白 PC-1/TNF-a;Figure 14. Insulin resistance in 50% of PCOS women appears to be secondary to a cell membrane-associated factor, presumably a serine/threonine kinase, that serine-phosphorylates the IR-inhibiting signaling. Serine phosphorylation of IRS-1 appears to be the mechanism for TNF -mediated insulin resistance. The membrane glycoprotein PC-1 also inhibits IR kinase activity, but it does not cause serine phosphorylation of the receptor. These are examples of a recently appreciated mechanism