CREB通过协同激活剂PGC-1调节肝脏葡萄糖生成
1Peptide Biology Laboratories, Salk Institute for Biological Studies, 10010 N Torrey Pines Road, La Jolla, California 92037-1002, USA.
Nature
|September 15, 2001
概括
循环AMP (cAMP) 响应元素结合 (CREB) 蛋白通过激活PGC-1,这是葡萄糖生成的关键因素,在禁食期间调节葡萄糖平衡. 这一途径对于预防禁食低血糖至关重要,可能与II型糖尿病有关.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子内分泌学分子内分泌学
- 基因表达 基因表达
背景情况:
- 哺乳动物的禁食会通过葡萄糖和葡萄糖皮质类药物触发葡萄糖生成.
- 对于协同诱导葡萄糖合成的精确分子机制尚不清楚.
- 了解这些途径对于代谢疾病研究至关重要.
研究的目的:
- 阐明CREB调节葡萄糖生成的机制.
- 确定PGC-1在CREB介导的葡萄糖平衡中的作用.
- 为了研究CREB,PGC-1和肝脏葡萄糖生成之间的联系.
主要方法:
- 在小鼠中进行基因破坏和过度表达研究.
- 对葡萄糖原性基因表达的分析.
- 在体内进行CREB调节测试.
- 暂时转染试验用于评估PGC-1功能.
主要成果:
- 缺乏或抑制CREB会导致禁食低血糖症和降低葡萄糖生成酶的表达.
- 在体内,CREB直接调节PGC-1的表达.
- 在CREB缺乏的小鼠中PGC-1过度表达恢复了葡萄糖平衡.
- PGC-1增强了PEPCK的葡萄糖皮质体诱导,这是一个关键的葡萄糖生成酶.
结论:
- 通过直接调节PGC-1,CREB激活了葡萄糖生成程序.
- PGC-1作为关键的联合激活剂,整合了cAMP和葡萄糖皮质体信号传递,用于肝脏的葡萄糖生成.
- 肝脏中CREB-PGC-1通路的失调可能会导致II型糖尿病的发病.
相关概念视频
Cell Specific Gene Expression
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...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
GPCRs Regulate Adenylyl Cylase Activity
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 cells.
Two...
Two...
cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Global Regulatory Systems
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...


