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Diabetes 53:S125-S129, 2004
© 2004 by the American Diabetes Association, Inc.

Section III: Mitochondria, Beta-Cell Function, and Type 2 Diabetes

ALS/Lt: A New Type 2 Diabetes Mouse Model Associated With Low Free Radical Scavenging Potential

Clayton E. Mathews1, Rebecca Bagley2, and Edward H. Leiter2

1 Department of Pediatrics, the University of Pittsburgh, Pittsburgh, Pennsylvania
2 The Jackson Laboratory, Bar Harbor, Maine

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 ß-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.

Address correspondence and reprint requests to Dr. Clayton E. Mathews, Diabetes Institute, 3460 5th Ave./Rangos Research Center, the University of Pittsburgh, Pittsburgh, PA 15213. E-mail: cem65{at}pitt.edu


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.