生物化学资料:UNIT V:Integration of Metabolism.pptVIP

生物化学资料:UNIT V:Integration of Metabolism.ppt

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* * * IRS-2 insulin receptor substrate-2 胰岛素受体底物2 * 磷脂酰肌醇3-激酶(PI3Ks)信号参与增殖、分化、凋亡和葡萄糖转运等多种细胞功能的调节;GSK3糖原合酶激酶3 蛋白激酶B(protein kinaseB,PKB)为原癌基因C—Akt的表达产物,是细胞内外磷脂酰肌醇3激酶(phosphoinositide 3 kinase,PI3K)信号通路中重要的激酶之一,在胰岛素刺激的葡萄糖摄取中起重要作用。PKB可诱导葡萄糖转运因子4(GLUT4)易位,促进肌肉和脂肪组织摄取葡萄糖,失活葡萄糖激酶3(GSK3),刺激糖原的合成,影响糖酵解和糖异生。从而维持血糖的稳定。 * The insulin signaling network. The full network is complex and can be divided into five levels: 1) activation of the insulin receptor tyrosine kinase and closely linked events; 2) phosphorylation of a family of substrate proteins; 3) interaction of the receptor and its substrates with several intermediate signaling molecules via SH2 (src homology 2) and other recognition domains; 4) activation of serine and lipid kinases, resulting in a broad range of phosphorylation-dephosphorylation events; and 5) regulation of the final biological effectors of insulin action, such as glucose transport, lipid synthesis, gene expression, and mitogenesis. The SH2 proteins link the insulin receptor substrate (IRS) proteins to a series of cascading reactions involving serine/threonine kinases and phosphatases such as the mitogen-activated protein (MAP) kinases, S6 kinases, and protein phosphatase-1A. These serine kinases act on enzymes such as glycogen synthase, transcription factors, and other proteins to produce many of the final biological effects of the hormone. In adipose tissue and muscle, insulin stimulation also increases glucose uptake by promoting translocation of an intracellular pool of glucose transporters to the plasma membrane. Exactly how this action is linked to the phosphorylation cascade is unknown, but several studies suggest that this important action of insulin, as well as most metabolic effects, is downstream of the enzyme phosphatidylinositol 3-kinase (PI 3-kinase). Other effects of insulin, such as stimulation of glycogen and lipid synthesis, occur through additional intracellular effects to stimulate the enzymes involved in these reactions. ATP—adeno

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