拉帕米辛的使用导致肌肉收缩功能下降和全身葡萄糖不耐受,同时导致骨肌肉Rictor减少,mTORC2成分,表达独立于年轻大鼠的能量摄入量
Satoru Ato1,2,3, Chieri Oya1, Riki Ogasawara1,2
1Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Nagoya, Japan.
PloS one
|December 5, 2024
概括
拉巴胺 (RAP) 模仿热量限制 (CR),但对大鼠的骨肌肉质量和功能产生负面影响. 与CR不同,RAP没有改善肌肉收缩功能,并且恶化了葡萄糖耐受性.
科学领域:
- 骨肌肉生理学 骨肌肉生理学
- 药理学 药理学是指药理学的学科.
- 代谢过程中的代谢.
背景情况:
- 新出现的证据表明,拉巴胺 (mTOR抑制剂) 可能模仿卡路里限制 (CR) 对于骨肌肉健康.
- 拉巴胺素 (RAP) 降低了食欲,但它对骨肌肉的影响与CR不同.
- 了解这些差异对于潜在的治疗应用至关重要.
研究的目的:
- 为了研究RAP和CR在年轻成年大鼠骨肌中的生理和分子差异.
- 为了比较RAP和配对养 (PF) 对肌肉质量,肌纤维大小和收缩功能的影响.
- 检查RAP对mTORC1信号传递,葡萄糖耐受性和相关基因表达的影响.
主要方法:
- 在年轻的成年大鼠中,RAP或PF给药四周.
- 快速糖解和缓慢氧化肌肉特征的分析.
- 评估足部 flexor 肌肉收缩功能.
- 测量mTORC1信号传递,全身葡萄糖耐受性和骨肌肉基因表达 (Rictor,hexokinase).
主要成果:
- RAP减少了快速糖解质的肌肉质量和肌纤维大小,独立于能量摄入.
- PF改善了脚部 flexor 肌肉功能,而RAP没有.
- 与快速氧化肌肉相比,RAP在缓慢氧化肌肉中显示出对mTORC1信号的更大抑制.
- RAP加剧了全身葡萄糖不耐受性,并减少了骨肌肉中的Rictor和hexokinase的表达.
结论:
- 与卡路里限制相比,Rapamycin的使用对年轻成年人骨肌肉有明显的和潜在的负面影响.
- RAP对肌肉质量,纤维大小和收缩功能产生负面影响,同时也会损害葡萄糖代谢.
- 这些发现突显了拉巴素和CR在骨肌肉生理学和新陈代谢方面的显著差异.
相关概念视频
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Oral Hypoglycemic Agents: Biguanides and Glitazones
172
Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
172


