细胞内膜网膜压力有助于哈希莫托甲状腺炎的胰岛素抵抗
Qing Zhou1, Li Yong Zhang2, Xue Lin Gao1
1Department of Endocrinology, Fujian Children's Hospital, Fujian Branch of Shanghai Children's Medical Center, Fujian Maternity and Child Health Hospital, Fuzhou, China.
Endocrine connections
|July 31, 2025
概括
哈西莫托甲状腺炎 (HT) 与胰岛素耐药性有关,可能是通过内分泌网膜 (ER) 压力. 在HT小鼠中抑制ER压力改善了胰岛素敏感性并减少了炎症.
科学领域:
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 哈西莫托甲状腺炎 (HT) 是一种常见的自身免疫性疾病.
- 在HT患者中,即使甲状腺功能正常,也经常观察到胰岛素耐药性.
- 细胞内膜网膜 (ER) 的压力与HT等自身免疫性疾病的发病有关.
研究的目的:
- 研究HT在小鼠模型中影响胰岛素抵抗的机制.
- 确定ER应激在HT相关胰岛素抵抗中的作用.
- 评估ER应激抑制在HT的治疗潜力.
主要方法:
- 用高剂量的和甲状腺蛋白注射来建立了Euthyroid HT小鼠模型.
- 小鼠接受了4-甲酸 (4-PBA) 治疗,这是一种ER压力抑制剂.
- 分析了关键蛋白质表达 (Bip,ATF6,IRE1,JNK,IRS-1,AKT) 和血清细胞因子水平 (TNF-α,IL-6).
主要成果:
- 在HT小鼠中,甲状腺和脂肪组织中的ER压力标志物 (Bip,ATF6,IRE1,JNK) 增加.
- 在HT小鼠中,胰岛素敏感性受损,由IRS-1和AKT酸化的降低证明.
- 在HT小鼠中,4-PBA治疗减轻了胰岛素抵抗,并降低了TNF-α和IL-6水平的升高.
结论:
- 哈西莫托的甲状腺炎与胰岛素抵抗的发展有关.
- 细胞内膜网膜应激在HT的胰岛素耐药性病变发生中发挥着重要作用.
- 针对ER压力可能提供一种治疗策略,用于管理HT的胰岛素抵抗.
相关概念视频
Role of ER in the Secretory Pathway
5.6K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
5.6K
Synthesis and Regulation of Thyroid Hormones
5.1K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
5.1K
Insulin: The Receptor and Signaling Pathways
1.5K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.5K
Regulation of the Unfolded Protein Response
2.6K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.6K
Functions of Thyroid Hormones
3.2K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
3.2K
Psychoneuroimmunology: Diabetes and Cancer
62
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
62


