Diabetes/metabolism research and reviews · 2002
Thiazolidinediones for the prevention of diabetes in the non-obese diabetic (NOD) mouse: implications for human type 1 diabetes.
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Beales Philip E, Pozzilli Paolo
Аннотация
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.
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.