Related Experiment Video
Updated: Jun 2, 2026
07:34
Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
SREBP-1c regulates glucose-stimulated hepatic clusterin expression
Gukhan Kim1, Geun Hyang Kim, Gyun-Sik Oh
1Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Biochemical and Biophysical Research Communications
|May 10, 2011
Summary
High glucose increases clusterin expression in liver cells by activating an intronic element. Sterol regulatory element binding protein-1c (SREBP-1c) is key to this glucose-induced regulation, not the typical ChREBP pathway.
Area of Science:
- Molecular Biology
- Metabolic Regulation
- Gene Expression
Background:
- Clusterin is a stress-response protein implicated in various biological processes and pathological conditions, including diabetes and metabolic syndrome.
- While clusterin's association with metabolic disorders is known, its regulation by specific metabolic signals like glucose remained unelucidated.
- Understanding how metabolic signals influence clusterin expression is crucial for comprehending its role in disease pathogenesis.
Purpose of the Study:
- To investigate the effects of glucose on hepatic clusterin expression.
- To identify the regulatory elements and transcription factors involved in glucose-mediated clusterin gene activation.
- To elucidate the mechanism by which metabolic signals regulate clusterin.
Main Methods:
- Primary hepatocytes and hepatoma cell lines were treated with varying glucose concentrations.
- Analysis of clusterin gene expression using promoter and intronic region reporter assays.
- Identification of glucose response elements (GlRE) and investigation of transcription factor binding (ChREBP, SREBP-1c) via electrophoretic mobility shift assays and chromatin immunoprecipitation.
Main Results:
- High glucose concentrations significantly increased clusterin expression in liver cells.
- The first intronic region, not the conventional promoter, was transcriptionally activated by high glucose.
- A novel glucose response element (GlRE) containing E-box motifs was identified, activated by sterol regulatory element binding protein-1c (SREBP-1c), not ChREBP, with glucose inducing SREBP-1c binding to this element.
Conclusions:
- Glucose stimulation upregulates hepatic clusterin expression through an intronic regulatory element.
- Sterol regulatory element binding protein-1c (SREBP-1c) plays a critical role in the metabolic regulation of clusterin gene expression by glucose.
- This study reveals a novel mechanism of metabolic control over clusterin, distinct from pathways typically involving ChREBP.
Related Concept Videos
01:58Cell 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...
01:28Insulin: The Receptor and Signaling Pathways
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 this inhibition is released...
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
01:02Glucose Homeostasis: Regulation of Blood Glucose
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
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 co-secreted in...
Insulin and C-peptide are co-secreted in...
01:25cAMP-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,...