Molecular mechanisms of insulin signal transduction and diabetas mellitus

GTP γ S诱导葡萄糖转运蛋白4型（GLUT4）从细胞内转运到细胞表面，增加脂肪细胞的葡萄糖摄取。负责易位的gtp结合蛋白仍有待鉴定。我们获得的证据表明，受体偶联Gq的激活可独立于胰岛素信号通路触发细胞中的GLUT4易位。去甲肾上腺素在表达gq偶联α -肾上腺素能受体的细胞中触发GLUT4易位。去甲肾上腺素刺激的GLUT4易位和通过Gq的葡萄糖摄取可能有助于棕色脂肪细胞产热和心肌细胞收缩性增强所需的燃料供应，两者都具有丰富的内源性GLUT4。体育锻炼诱导骨骼肌中GLUT4从细胞内池转运到细胞表面，并通过胰岛素不依赖途径增加葡萄糖摄取。然而，其分子机制还有待进一步研究。一些研究表明，缓激肽从收缩肌肉局部释放，可能是导致GLUT4易位和骨骼肌葡萄糖转运增加的原因。我们发现缓激肽直接触发GLUT4易位，并在这些细胞中以剂量依赖的方式增加葡萄糖摄取速率。缓激素可能是运动刺激骨骼肌葡萄糖摄取的因素之一。AMP活化蛋白激酶（AMPK）作为代谢传感器监测细胞AMP和ATP水平。去甲肾上腺素和缓激素也分别激活表达G(q)偶联α 1b肾上腺素受体和缓激素受体的细胞中的AMPK α 1。AMPK α 1被G(q)偶联受体特异性激活。G(q)偶联受体通过胰岛素不依赖的途径传递GLUT4易位和葡萄糖摄取的信号。然而，用5-氨基咪唑-4-羧酰胺- 1 - β -d-核呋喃苷直接激活AMPK α 1并不会触发GLUT4易位。因此，通过G(q)激活AMPK α 1并不足以触发GLUT4易位或刺激葡萄糖摄取。少

GTP γ S induces the translocation of glucose transporter type 4 (GLUT4) from an intracellular pool to the cell surface and increases glucose uptake in adipocytes. The GTP-binding protein(s) responsible for the translocation has remained to be identified. We obtained evidence that the activation of receptor-coupled Gq triggered GLUT4 translocation in cells, independently of insulin signaling pathway(s). Norepinephrine triggered GLUT4 translocation in cells expressing the Gq-coupled alphal -adrenergic receptor. The norepinephrine-stimulated GLUT4 translocation and glucose uptake via Gq may possibly contribute to the fuel supply required for thermogenesis in brown adipocytes and for the enhanced contractility in cardiomyocytes, both of which have an abundant endogenous GLUT4.Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose uptake via an insulin-independent pathway. However, the molecular mechanism rem … More ains to be identified. Some studies have suggested that bradykinin is locally released from contracting muscles and may be responsible for GLUT4 translocation and the increase of glucose transport in skeletal muscles. We found that bradykinin directly triggered GLUT4 translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.The AMP-activated protein kinase (AMPK) functions as a metabolic sensor that monitors cellular AMP and ATP levels. Norepinephrine and bradykinin also activated AMPK α 1 in cells expressing G(q)-coupled α 1b-adrenergic receptor and bradykinin receptor, respectively. AMPK α 1 is activated specifically by stimulation of G(q)-coupled receptors. G(q)-coupled receptors transmit the signal for GLUT4 translocation and glucose uptake through an insulin-independent pathway. However, direct activation of AMPK α 1 with treatment of 5-aminoimidazole-4-carboxamide- 1 -beta-d-ribofuranoside did not trigger GLUT4 translocation. Thus, activation of AMPK α 1 via G(q) is not sufficient to trigger GLUT4 translocation or stimulate glucose uptake. Less