胰岛素抵抗与多囊卵巢综合征.ppt

（优选）胰岛素抵抗与多囊卵巢综合征
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Figure 2. Section of a polycystic ovary with multiple subscapular follicular cyst serine phosphorylation inhibits it.
胰岛素的作用机理（2）
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胰岛素抵抗的机理(1)
受体与胰岛素的结合或者受体亲和力无改变
50% PCOS-ser : IR 酪氨酸磷酸化 或 IR 丝氨酸磷酸化
50% PCOS-nl: IR下游信号传导受阻 (IRS-1 的磷酸化； PI3-K的活性 ）
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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.
胰岛素抵抗的机理（2）
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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
胰岛素抵抗的机理（3）
抑制 IR 酪氨酸激酶活性
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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 for insulin resistance secondary to factors regulating the receptor’s tyrosine kinase activity.
胰岛素抵抗的机理（4）
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. a normal (control), a PCOS woman with normal insulin-stimulated tyrosine phosphorylation (PCOS-nl) and a PCOS woman with high basal autophosphorylation on serine residues (PCOS-ser); S-serine, Y-tyrosine. Basal autophosphorylation is increased and there is minimal further insulin-stimulated phosphorylation in the PCOS-ser b-subunits. The high basal phosphorylation represents phosphoserine, and phosphotyrosine content does not increase in response to insulin in the PCOS-ser b-subunits.
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