Related Experiment Video
Updated: Oct 12, 2025
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Orotic acid protects pancreatic β cell by p53 inactivation in diabetic mouse model
Yohei Fushimura1, Atsushi Hoshino1, Satoru Furukawa2
1Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Abstract:
Impairment of pancreatic β cells is a principal driver of the development of diabetes. Restoring normal insulin release from the β cells depends on the ATP produced by the intracellular mitochondria. In maintaining mitochondrial function, the tumor suppressor p53 has emerged as a novel regulator of metabolic homeostasis and participates in adaptations to nutritional changes. In this study, we used orotic acid, an intermediate in the pathway for de novo synthesis of the pyrimidine nucleotide, to reduce genotoxicity. Administration of orotic acid reduced p53 activation of MIN6 β cells and subsequently reduced β cell death in the db/db mouse. Orotic acid intake helped to maintain the islet size, number of β cells, and protected insulin secretion in the db/db mouse. In conclusion, orotic acid treatment maintained β cell function and reduced cell death, and may therefore, be a future therapeutic strategy for the prevention and treatment of diabetes.
Insights
Orotic acid protects pancreatic beta cells from death and preserves insulin secretion, offering a potential new strategy for diabetes treatment and prevention.
Area of Science:
- Metabolic homeostasis
- Mitochondrial function
- Diabetes pathogenesis
Background:
- Pancreatic beta cell impairment drives diabetes development.
- Mitochondrial ATP production is crucial for insulin release.
- Tumor suppressor p53 regulates metabolic homeostasis.
Purpose of the Study:
- To investigate orotic acid's effect on beta cell function and survival.
- To explore orotic acid's role in mitigating diabetes-related beta cell death.
Main Methods:
- Utilized orotic acid, a pyrimidine nucleotide synthesis intermediate.
- Administered orotic acid to MIN6 beta cells and db/db mice.
- Assessed p53 activation, beta cell death, islet size, and insulin secretion.
Main Results:
- Orotic acid reduced p53 activation and beta cell death in db/db mice.
- Orotic acid maintained islet size and beta cell number.
- Orotic acid protected insulin secretion in the db/db mouse model.
Conclusions:
- Orotic acid treatment preserves pancreatic beta cell function and viability.
- Orotic acid demonstrates potential as a therapeutic strategy for diabetes.
- Further research into orotic acid for diabetes prevention and treatment is warranted.
More Related Videos
07:44Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation
Published on: August 7, 2015
12:33A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination
Published on: June 25, 2014