Thiazolidinediones for the prevention of diabetes in the non-obese diabetic (NOD) mouse: implications for human type 1 diabetes.

Abstract

BACKGROUND:

Thiazolidinediones (TZDs) are a recently introduced generation of drugs acting as receptor agonists to reduce insulin resistance and used currently in combination with other hypoglycaemic agents for the treatment of type 2 diabetes. In addition, TZDs possess anti-inflammatory properties that make them of interest for reducing the T-cell inflammation occurring in the islets in type 1 diabetes.

METHODS:

The action of TZD treatment on diabetes incidence in the non-obese diabetic (NOD) mouse was studied by investigating the effect of rosiglitazone (RGL) (400 mg/kg body weight by gavage) from 3 weeks of age (soon after weaning) onwards and comparing its effect to that of troglitazone (TGL) given by the same route.

RESULTS:

We found that RGL and TGL both significantly reduced diabetes incidence by >50% in the NOD mouse compared to litter-matched control NOD mice (p<0.05 and p<0.01, respectively). However, the withdrawal of TGL from the market due to hepatotoxicity led us to re-analyse our data for toxic liver effects. We found that TGL was more toxic to mice than RGL (causing ten deaths as compared with one death).

CONCLUSION:

RGL reduces diabetes incidence in the NOD mouse model of type 1 diabetes. This may be an effect resulting from its action as on inhibitor of pro-inflammatory genes such as cytokines and metabolic proteases. Its use may be considered for trials designed to protect beta-cell function in humans, especially in patients with latent autoimmune diabetes of adults (LADA) and also for disease prevention.

• Authors: Philip E Beales, Paolo Pozzilli
• Journal: Diabetes/metabolism research and reviews (Diabetes Metab Res Rev) 2002 Mar-Apr Vol. 18 Issue 2 Pg. 114-7 ISSN: 1520-7552 [Print] England
• PMID: 11994902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 John Wiley & Sons, Ltd.

Chemical References

• Chromans
• Hypoglycemic Agents
• Thiazoles
• Thiazolidinediones
• Rosiglitazone
• 2,4-thiazolidinedione
• Troglitazone

Topics

• Animals
• Chromans (therapeutic use)
• Diabetes Mellitus, Type 1 (drug therapy, genetics)
• Disease Models, Animal
• Female
• Hypoglycemic Agents (therapeutic use)
• Incidence
• Male
• Mice
• Mice, Inbred NOD
• Rosiglitazone
• Thiazoles (therapeutic use)
• Thiazolidinediones
• Troglitazone