ALS/Lt: a new type 2 diabetes mouse model associated with low free radical scavenging potential.
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.
Mathews
Clayton E
CE
Department of Pediatrics, the University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. cem65@pitt.edu
Bagley
Rebecca
R
Leiter
Edward H
EH
D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013997:Time Factors
D001786:Blood Glucose; D016166:Free Radical Scavengers