Related Experiment Video
Updated: Sep 13, 2025
Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress
Xueyan Li1,2, Yunan Chen2, Lei Su2
1The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Department of Nutrition, School of Public Health of Guizhou Medical University, Guiyang, 561000, China.
Background:
Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms.
Methods:
Both in vivo hyperuricemia diet-induced mouse models and in vitro pancreatic β cell models were utilized.
Results:
A progressive decrease in glucose-stimulated insulin secretion and increase in β cell apoptosis were observed in the hyperuricemia diet-induced mouse model, and these could be effectively restored by urate-lowering therapy. The dose- and time-dependent direct effects of uric acid on β cell apoptosis and insulin secretion were further confirmed in both INS-1E cells and primary isolated islets. Mechanistically, the primary role of expression of the endoplasmic reticulum stress marker C/EBP homologous protein (CHOP) was detected by RNA sequencing, and the inflammatory factor NLRP3 and pro-apoptotic genes were significantly upregulated by uric acid treatment.
Conclusions:
Together, our findings indicate a direct crosstalk between uric acid and β cells via CHOP/NLRP3 pathway, providing a new understanding of the diabetogenic effect of uric acid.
Related Concept Videos
01:24Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
01:37The Unfolded Protein Response
01:27Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are...
01:31Regulation of the Unfolded Protein Response
01:27Acute Pancreatitis I: Introduction
Acute pancreatitis is characterized by rapid inflammation of the pancreas, often caused by factors like gallstone blockage or excessive alcohol consumption. Chronic pancreatitis, on the other hand, is a slow, progressive inflammation that may result from long-term alcohol abuse, obstructions in the pancreatic duct, or genetic factors.
The causes of acute pancreatitis include:
01:32Export of Misfolded Proteins out of the ER