Related Experiment Video
Updated: Aug 15, 2026
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Role of metallothionein in 4-aminopyrazolo[3,4-d]pyrimidine-administered mouse pancreas
T Minami1, H Nakagawa, S Yoshimoto
1Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Abstract:
Pancreatic metallothionein (MT) and zinc levels were measured after the administration of 4-aminopyrazolo(3,4-d)pyrimidine (4APP) to mice to determine the role of pancreatic MT. 4APP was found to increase the pancreatic MT level dose-dependently; the pancreatic MT level in mice administered 175 mg/kg of 4APP was 3.9 fold higher than that in control mice. When 40 mg/kg or less of 4APP was administered, the zinc concentration of the pancreatic cytosol fraction did not differ from that in control mice, while after 175 mg/kg of 4APP it was 1.7-fold higher. There was no difference in plasma glucose and insulin levels between the controls and mice administered 175 mg/kg of 4APP, although the plasma alpha-amylase activity was reduced in the latter. Moreover, a linear negative relationship was observed between pancreatic MT level and plasma alpha-amylase activity (r = -0.795, p < 0.01). These findings suggest that pancreatic MT is affected by the disruption of the exocrine function in 4APP-administered mouse pancreas.
Insights
Pancreatic metallothionein (MT) levels increase with 4-aminopyrazolo(3,4-d)pyrimidine (4APP) administration, impacting pancreatic exocrine function and reducing alpha-amylase activity.
Area of Science:
- Biochemistry
- Toxicology
- Pancreatic Physiology
Background:
- Metallothionein (MT) plays a crucial role in cellular defense against heavy metals and oxidative stress.
- The specific role of pancreatic MT in regulating exocrine function is not fully understood.
- 4-aminopyrazolo(3,4-d)pyrimidine (4APP) is a compound known to induce various biological effects.
Purpose of the Study:
- To investigate the role of pancreatic metallothionein (MT) in response to 4-aminopyrazolo(3,4-d)pyrimidine (4APP) administration.
- To determine the effect of 4APP on pancreatic MT and zinc levels.
- To explore the relationship between pancreatic MT and exocrine function markers.
Main Methods:
- Mice were administered varying doses of 4APP.
- Pancreatic MT and zinc levels were quantified.
- Plasma glucose, insulin, and alpha-amylase activity were measured.
Main Results:
- 4APP administration increased pancreatic MT levels in a dose-dependent manner.
- Elevated pancreatic MT levels correlated with increased pancreatic zinc concentration at higher 4APP doses.
- A significant negative correlation was observed between pancreatic MT levels and plasma alpha-amylase activity.
Conclusions:
- Pancreatic MT is responsive to 4APP exposure.
- The findings suggest that 4APP disrupts pancreatic exocrine function, potentially mediated by changes in MT and zinc homeostasis.
- Pancreatic MT may play a role in modulating the exocrine response to toxic insults.
