Nrf2抑制调节小鼠胰岛素瘤细胞中的细胞内脂质积累,并改善胰岛素分泌功能
Alpana Mukhuty1, Samanwita Mandal1, Chandrani Fouzder1
1Cell Signaling Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan, 731 235, India.
Molecular and cellular endocrinology
|November 24, 2023
概括
费图因-A通过增加CD36表达来促进胰腺β细胞中的脂肪积累,导致功能障碍和2型糖尿病风险. 向Nrf2可以减少脂质的积累,并恢复β细胞的功能.
科学领域:
- 内分泌学 在内分泌学.
- 代谢性疾病研究研究
- 细胞生物学 细胞生物学
背景情况:
- 胰腺β细胞脂毒性是2型糖尿病发展的关键因素.
- 肥胖的标志物Fetuin-A与代谢失调有关.
- 脂肪酸转位酶/CD36在细胞脂质的吸收和储存中起作用.
研究的目的:
- 调查Fetuin-A在促进胰腺β细胞中的脂质积累中的作用.
- 阐明脂肪酸转位酶/CD36和Nrf2在Fetuin-A诱导的β细胞功能障碍中的参与.
- 探索向Nrf2以恢复β细胞功能的潜力.
主要方法:
- 在体外研究中,使用暴露于棕酸盐和Fetuin-A.的MIN6细胞.
- 对脂质基因表达的分析 (CD36,PGC1α,PPARγ,SREBP1).
- 流细胞计,油红色染色,免疫涂抹,免疫光和siRNA介导的Nrf2抑制.
主要成果:
- 棕酸盐和Fetuin-A暴露增加了细胞内脂质,并在MIN6细胞中降低了胰岛素分泌.
- 费图因-A增强了CD36表达和膜局部化,与脂质积累相关.
- 观察到nrf2激活,其抑制减少了脂质生成,细胞亡,恢复了胰岛素分泌和β细胞基因表达.
结论:
- 费图因-A通过通过CD36和Nrf2促进脂质积累,有助于胰腺β细胞功能障碍.
- 抑制Nrf2成为改善β细胞脂毒性和恢复功能的潜在治疗策略.
- 这项研究突出了一个新的机制,将Fetuin-A,脂质代谢和β细胞衰竭与2型糖尿病相关联.
相关概念视频
01:28Insulin: The Receptor and Signaling Pathways
1.2K
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...
1.2K
01:31Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
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...
3.6K