通过氧化对β细胞选择性调节基因表达
Aaron Naatz1, Chay Teng Yeo1, Neil Hogg2
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
概括
来自可诱导氧化合成酶 (iNOS) 的氧化 (NO) 通过影响β细胞基因表达影响胰岛素分泌. 贝塔细胞独特地对狭窄的NO度范围做出反应,与其他细胞类型不同.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 内分泌学 在内分泌学.
- 代谢过程中的代谢.
背景情况:
- 由可诱导氧化合成酶 (iNOS) 生产的氧化 (NO) 抑制了由葡萄糖刺激的胰岛素分泌.
- NO干扰线粒体的氧化代谢,蛋白质合成和β细胞中的DNA完整性.
- 细胞因子利用NO调节兰格汉斯函数的小岛.
研究的目的:
- 调查NO对关键β细胞反应基因表达的时间和度相关影响.
- 为了确定在β细胞中引起反应的NO的特定度范围.
- 将NO对β细胞的影响与其对其他细胞类型的影响进行比较.
主要方法:
- 用不同的NO度对β细胞进行处理.
- 对Gadd45α,Puma,Hmox1,Hsp70,Chop和Ppargc1α的基因表达的分析.
- 在非β细胞 (包括α细胞,纤维细胞和巨细胞) 中进行比较研究.
主要成果:
- NO刺激β细胞基因表达在约0.5-1μM的狭窄度范围内,与iNOS生产水平一致.
- 较高的NO度 (>1μM) 抑制β细胞基因表达,与抑制的线粒体氧化代谢有关.
- 贝塔细胞对NO的反应是有选择性的,与非贝塔细胞中观察到的度依赖作用不同.
结论:
- 贝塔细胞对NO具有独特的,狭窄的度依赖的敏感性,对调节胰岛素分泌至关重要.
- 这些发现突显了胰腺β细胞中NO信号的选择性.
- 了解这种狭窄的响应窗口对于了解β细胞功能和代谢疾病中的功能障碍至关重要.
相关概念视频
Nitric Oxide Signaling Pathway
5.0K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
5.0K
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
GPCRs Regulate Adenylyl Cylase Activity
5.5K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.5K
Regulation of Expression at Multiple Steps
902
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
902
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.2K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.2K
Regulation of Expression Occurs at Multiple Steps
22.7K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.7K


