Title

ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential.

Document Type

Article

Publication Date

2004

Keywords

Animals, Blood-Glucose, Body-Weight, Comparative-Study, Diabetes-Mellitus-Experimental, Diabetes-Mellitus-Type-II, Disease-Models-Animal, Free-Radical-Scavengers, Kinetics, Male, Mice, Mice-Mutant-Strains, SUPPORT-U-S-GOVT-P-H-S, Time-Factors

JAX Source

Diabetes 2004 Feb; 53(Suppl 1):S125-9.

Abstract

Outbred CD-1 mice carry a spectrum of genetic susceptibilities for obesity and type 2 diabetes. ALS is an inbred strain with low antioxidant defenses produced by inbreeding CD-1 mice, with selection for susceptibility to alloxan, a generator of highly reactive oxygen free radicals and a potent beta-cell toxin. The objective of this study was to determine if the low ability to diffuse free radical stress would contribute to spontaneous type 2 diabetes development in alloxan-untreated males. Indeed, both hyperinsulinemia and impaired glucose tolerance developed spontaneously between 6 and 8 weeks of age in alloxan-untreated males. Further aging was accompanied by increases in body mass, progressively more severe hyperinsulinemia, and development of overt hyperglycemia. Transition from impaired glucose tolerance to overt hyperglycemia correlated with a decreased ratio of reduced to oxidized glutathione. Evidence that the increased oxidative burden elicited the type 2 diabetes syndrome was obtained by the systemic elevation of the antioxidative capacity through daily administration of R-lipoic acid. R-lipoic acid (30 mg/kg) prevented hyperglycemia, reduced insulin levels, and increased free radical scavenging potential. This mouse model with reduced ability to diffuse free radical stress is of obvious interest because free radical-mediated damage is implicated in the pathogenesis and complications of both type 1 and type 2 diabetes.