This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cardinal, J. W. Articles by Cameron, D. P. Search for Related Content PubMed PubMed Citation Articles by Cardinal, J. W. Articles by Cameron, D. P.

Differential Metabolite Accumulation May Be the Cause of Strain Differences in Sensitivity to Streptozotocin-Induced ß Cell Death in Inbred Mice¹

Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Woolloongabba, Brisbane 4102, Australia; School of Life Sciences Queensland University of Technology, Brisbane 4001, Australia

Address all correspondence and requests for reprints to: John W. Cardinal, Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane 4102, Australia.

Inbred strains of mice vary in their sensitivity to the diabetogenic effects of streptozotocin (STZ). To investigate the basis for this strain difference we exposed islet cells from two strains of mice that differ in sensitivity to the drug. We examined them morphologically and measured islet NAD + NADH content, streptozotocin metabolite accumulation, glucose transport capacity, Glut2 levels and medium nitrite accumulation.

C57bl/6J mice were more sensitive to STZ than Balb/c mice as judged by the extent of pancreatic insulin depletion and ß cell death, in vivo and in vitro. The mode of cell death was necrosis. After a 30-min in vitro exposure to the drug the more sensitive C57bl/6J islets contained higher levels of streptozotocin metabolites and less NAD + NADH than the more resistant Balb/c islets. The lack of any strain differences in 3-O-methyl glucose transport, Glut2 levels and medium nitrite accumulation suggested that STZ transport and nitric oxide metabolism were not responsible for differences in STZ sensitivity and metabolite accumulation.

Thus the strain differences in STZ sensitivity appears to be due to intracellular events within the ß cell occurring after STZ transport and before NAD + NADH depletion. STZ metabolite accumulation appears to be associated with STZ sensitivity. Further studies are warranted to determine if differential STZ metabolite accumulation is responsible for STZ sensitivity.

This article has been cited by other articles:

				S. M. Clee and A. D. Attie The Genetic Landscape of Type 2 Diabetes in Mice Endocr. Rev., February 1, 2007; 28(1): 48 - 83. [Abstract] [Full Text] [PDF]

				J. W. Cardinal, G. P. Margison, K. J. Mynett, A. P. Yates, D. P. Cameron, and R. H. Elder Increased Susceptibility to Streptozotocin-Induced {beta}-Cell Apoptosis and Delayed Autoimmune Diabetes in Alkylpurine- DNA-N-Glycosylase-Deficient Mice Mol. Cell. Biol., August 15, 2001; 21(16): 5605 - 5613. [Abstract] [Full Text] [PDF]