p38是丝裂原活化蛋白激酶家族中的成员之一,大量研究显示p38在能量代谢中具有广泛的作用.p38参与脂肪组织、骨骼肌、胰岛细胞和肝脏等组织、器官的能量代谢,这些组织、器官都是控制能量代谢的主要组织与器官.在白色脂肪组织,p38对脂肪细胞分化和葡萄糖摄取的重要作用是一致公认的,尽管p38对脂肪细胞葡萄糖摄取究竟是促进还是抑制至今尚未定论;在棕色脂肪组织,p38对解偶联蛋白-1基因转录起促进作用.在骨骼肌,虽然p38对葡萄糖摄取的作用仍有争议,但p38对骨骼肌细胞分化和骨骼肌线粒体生成的重要作用是非常肯定的.在胰岛细胞,p38似乎与细胞凋亡有关;p38还可能控制胰岛素原基因转录,但对胰岛素分泌无明显作用.在肝脏,p38在肝脏的糖、脂代谢中起核心作用,一方面,p38通过抑制肝脏糖原合成,增加肝脏糖异生,使血糖升高;另一方面,p38通过抑制肝脏脂肪合成、促进脂肪酸在肝脏的氧化代谢,从而抑制脂肪在肝脏的贮存;另外,p38还通过调节低密度脂蛋白受体基因表达和胆汁代谢对胆固醇代谢起关键作用.p38不仅参与心肌细胞的各种生理、病理过程;也通过影响单核-巨噬细胞、血管内皮细胞和血管平滑肌细胞参与动脉粥样硬化斑块的形成.%p38 mitogen-activated protein kinase (p38) is a member of MAP kinase family. Its widespectrum roles in the control of energy metabolism have been indicated in numerous studies. P3 8 participates in the energy metabolism in all major tissues/organs involved in the control of energy metabolism, including adipose tissue, skeletal muscles, islet cells, and liver. In white adipose tissue, p38 plays an important role in adipose differentiation and glucose uptake although it is still inconclusive whether this role of p38 is stimulatory or inhibitory. The stimulatory role of p38 in transcription of the uncoupling protein 1 ( UCP1 ) gene in brown adipose tissue is relatively clear. A fundamental role for p38 in the differentiation of skeletal muscles and mitochondrial biogenesis in skeletal muscles is rather definitive although the role of p3 8 in glucose uptake of skeletal muscles remains controversial. In islet cells, p38 appears to be involved in β-cell apoptosis. P38 has been indicated in the control of preproinsulin gene transcription, but remains controversial. However, it seems clear that p38 does not play a significant role in insulin secretion. In the liver, p38 plays a central role in hepatic glucose and lipid metabolism. Activation of p38 participates in the processes to increase blood glucose levels through reducing glycogen synthesis and increasing hepatic gluconeogenesis. P38 appears to prevent fat storage by inhibiting hepatic lipogenesis and promoting fatty acid oxidation in the liver. Additionally, p38 may play a critical role in cholesterol metabolism by regulating expression of the LDLR gene and bile metabolism. P38 does not only participate in various physiological and pathophysiological processes in cardiomyocytes, but also is heavily involved in the development of atherosclerotic lessions through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells.
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