绝经前期 - 通过5-HT失调诱导的胰岛素抵抗
Yu Chen1, Jingwen Yu2, Chao Liu2
1Research Center of Endocrinology and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu, China.
绝经前期的卵巢衰竭会破坏血清素 (5-HT) 水平,损害胰岛素敏感性和肝脏胰岛素信号传递. 这突显了肠肝血清能通信是绝经期间代谢功能障碍的关键因素.
科学领域:
- 生殖内分泌学 生殖内分泌学
- 代谢生理学 代谢生理学
- 神经内分泌学神经内分泌学
背景情况:
- 更年期过渡增加了代谢功能障碍的风险,不清楚的机制将卵巢衰竭与胰岛素抵抗联系在一起.
- 血管运动症状是代谢风险标志物,但失调的血清激素信号可能会影响葡萄糖平衡独立于雌激素.
- 早期的绝经前期生理学涉及毛囊枯竭和升高的毛囊刺激激素,与保存的雌激素.
研究的目的:
- 为了研究周年绝经期卵巢衰竭对胰岛素敏感性,血清素水平和肝脏胰岛素信号传递的影响.
- 探讨在更年期过渡期间对代谢功能障碍中失调的血清激素信号传递的作用.
- 确定潜在的治疗目标,以减轻绝经前妇女糖尿病风险.
主要方法:
- 使用4 - 乙烯基环二氧化物 (VCD) 的小鼠模型模仿早期的绝经前期生理学.
- 在接受VCD治疗的小鼠中评估了胰岛素敏感性,血清和肝脏中血清激素 (5-HT) 水平,肝脏脂质含量和胰岛素信号标记物.
- 对AML-12肝细胞进行了体外实验,以评估5-HT对生命力,脂质积累和胰岛素信号传递的影响 (IRS1/AKT酸化).
主要成果:
- 接受VCD治疗的小鼠表现出胰岛素敏感性受损,尽管体重和代谢参数正常.
- 在VCD小鼠中,循环和肝脏5-HT水平显著降低.
- 在体外,5-HT剂量依赖性影响肝细胞活力,并通过增加p-IRS1/IRS1和减少p-AKT/AKT而破坏胰岛素信号传递,而不会改变脂质含量.
结论:
- 绝经前期的卵巢衰竭会破坏外围的5-HT稳态,导致肝脏胰岛素信号受损,而不依赖于脂肪或肥胖症.
- 肠 - 肝血清激素通信是新的贡献者在更年期过渡期间代谢脆弱性.
- 周围的5-HT通路代表了在经历绝经前症状的妇女中管理糖尿病风险的潜在治疗点.
更多相关视频
08:47Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
Published on: December 7, 2017
08:32Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
相关概念视频
Menopause
Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
Insulin: The Receptor and Signaling Pathways
Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Insulin: Dosing Regimen and Adverse Effects
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
Oral Hypoglycemic Agents: Biguanides and Glitazones
