[代谢综合征和2型糖尿病的脑瘦素信号系统及其功能状态]。

A O Shpakov
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引用次数: 0

摘要

脑瘦素信号系统在摄食行为、外周代谢、神经和内分泌系统功能的调节中起着关键作用,该系统的紊乱可导致代谢紊乱,包括代谢综合征(MS)和2型糖尿病(DM2)。该系统由脂肪细胞产生的瘦素激活,然后通过血脑屏障进入大脑,在那里瘦素与瘦素受体OBRb结合。这导致酪氨酸激酶JAK2的激活,JAK2磷酸化位于受体细胞质区域的含有酪氨酸的位点,从而刺激磷脂酰肌醇-3激酶、转录因子STAT3和STAT5、磷酸酶SHP2和丝裂原活化蛋白激酶的活性。功能活性瘦素受体数量的减少和神经元细胞中瘦素级联下游组分的干扰导致瘦素抵抗的发展。由于下丘脑神经元中的瘦素系统与胰岛素、黑素-诺皮质素、多巴胺能等信号系统密切相关,因此瘦素抵抗在中枢神经系统和外周神经系统中诱发了许多功能障碍。脑瘦素系统功能的恢复是治疗和预防代谢性疾病(包括MS和DM2)的有前途的方法之一。本文对MS和DM2中瘦素信号系统的结构和功能组织、其功能、与其他脑信号系统的相互作用、中枢性瘦素抵抗的原因和影响以及恢复下丘脑瘦素系统功能的途径进行了分析。关键词:瘦素,瘦素抵抗,下丘脑,jak2激酶,瘦素受体,糖尿病,代谢综合征,黑素皮质素系统,磷酸酶抑制剂
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[THE BRAIN LEPTIN SIGNALING SYSTEM AND ITS FUNCTIONAL STATE IN METABOLIC SYNDROME AND TYPE 2 DIABETES MELLITIS].

The brain leptin signaling system has a key role in regulation of feeding behavior, peripheral metabo- lism, functions of the nervous and endocrine systems, and disturbances in this system lead to metabolic disorders, including metabolic syndrome (MS) and type 2 diabetes mellitus (DM2). This system is activa- ted by leptin produced by adipocytes and then penetrates into brain through the blood-brain barrier, where leptin binds to leptin receptors OBRb. This leads to activation of tyrosine kinase JAK2, which phosphory- lates tyrosine-containing sites located in the cytoplasmic domain of the receptor, resulting in stimulation of activity of phosphatidylinositol-3-kinase, the transcription factors STAT3 and STAT5, phosphatase SHP2, and mitogen-activated protein kinase. Decrease in number of functionally active leptin receptors and disturbances in the downstream components of leptin cascades in neuronal cells lead to development of leptin resistance. Since the leptin system in hypothalamic neurons is closely linked to the insulin, mela- nocortin, dopaminergic and other signaling systems, leptin resistance induces a lot of functional disorders in the CNS and on the periphery. The restoration of the brain leptin system functions is one of the promi- sing approaches to treatment and prevention of metabolic disorders, including MS and DM2. The review analyzes data on structural and functional organization of the leptin signaling system, its functional, interaction with other brain signaling systems, the causes and effects of central leptin resistance, as well as the approaches to restore the functions of the hypothalamic leptin system in MS and DM2. Key words: leptin, leptin resistance, hypothalamus, JAK2-kinase, leptin receptor, diabetes mellitus, metabolic syndrome, melanocortin system, phosphatase inhibitor.

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