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胰岛素:胰腺β细胞与下丘脑之间的联系。

Insulin: A connection between pancreatic β cells and the hypothalamus.

作者信息

De la Cruz-Concepción Brenda, Flores-Cortez Yaccil Adilene, Barragán-Bonilla Martha Isela, Mendoza-Bello Juan Miguel, Espinoza-Rojo Monica

机构信息

Molecular and Genomic Biology Laboratory, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo 39070, Guerrero, Mexico.

出版信息

World J Diabetes. 2023 Feb 15;14(2):76-91. doi: 10.4239/wjd.v14.i2.76.

Abstract

Insulin is a hormone secreted by pancreatic β cells. The concentration of glucose in circulation is proportional to the secretion of insulin by these cells. In target cells, insulin binds to its receptors and activates phosphatidylinositol-3-kinase/protein kinase B, inducing different mechanisms depending on the cell type. In the liver it activates the synthesis of glycogen, in adipose tissue and muscle it allows the capture of glucose, and in the hypothalamus, it regulates thermogenesis and appetite. Defects in insulin function [insulin resistance (IR)] are related to the development of neurodegenerative diseases in obese people. Furthermore, in obesity and diabetes, its role as an anorexigenic hormone in the hypothalamus is diminished during IR. Therefore, hyperphagia prevails, which aggravates hyper-glycemia and IR further, becoming a vicious circle in which the patient cannot regulate their need to eat. Uncontrolled calorie intake induces an increase in reactive oxygen species, overcoming cellular antioxidant defenses (oxidative stress). Reactive oxygen species activate stress-sensitive kinases, such as c-Jun N-terminal kinase and p38 mitogen-activated protein kinase, that induce phos-phorylation in serine residues in the insulin receptor, which blocks the insulin signaling pathway, continuing the mechanism of IR. The brain and pancreas are organs mainly affected by oxidative stress. The use of drugs that regulate food intake and improve glucose metabolism is the conventional therapy to improve the quality of life of these patients. Currently, the use of antioxidants that regulate oxidative stress has given good results because they reduce oxidative stress and inflammatory processes, and they also have fewer side effects than synthetic drugs.

摘要

胰岛素是胰腺β细胞分泌的一种激素。循环中的葡萄糖浓度与这些细胞分泌的胰岛素成正比。在靶细胞中,胰岛素与其受体结合并激活磷脂酰肌醇-3-激酶/蛋白激酶B,根据细胞类型诱导不同的机制。在肝脏中,它激活糖原的合成;在脂肪组织和肌肉中,它促进葡萄糖的摄取;在下丘脑中,它调节产热和食欲。胰岛素功能缺陷(胰岛素抵抗,IR)与肥胖人群神经退行性疾病的发生有关。此外,在肥胖和糖尿病中,在胰岛素抵抗期间,其在下丘脑中作为食欲抑制激素的作用减弱。因此,多食占主导,这进一步加重了高血糖和胰岛素抵抗,形成恶性循环,患者无法调节自己的进食需求。不受控制的热量摄入会导致活性氧增加,超过细胞抗氧化防御能力(氧化应激)。活性氧激活应激敏感激酶,如c-Jun氨基末端激酶和p38丝裂原活化蛋白激酶,这些激酶会诱导胰岛素受体丝氨酸残基的磷酸化,从而阻断胰岛素信号通路,延续胰岛素抵抗机制。大脑和胰腺是主要受氧化应激影响的器官。使用调节食物摄入和改善葡萄糖代谢的药物是改善这些患者生活质量的传统疗法。目前,使用调节氧化应激的抗氧化剂已取得良好效果,因为它们可减轻氧化应激和炎症过程,且副作用比合成药物少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c54c/10011898/72708312774f/WJD-14-76-g001.jpg

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