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ORIGINAL RESEARCH ARTICLE

Tetrathiomolybdate Is Partially Protective Against Hyperglycemia in Rodent Models of Diabetes

Chunhua Zeng^*, Guoqing Hou^*, Robert Dick^* and George J. Brewer^*,,1

^* Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109; and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109

To whom requests for reprints should be addressed at ¹ University of Michigan Medical School, 5024 Kresge Bldg. II, Ann Arbor, MI 48109-0534. E-mail: brewergj{at}umich.edu

The objective was to evaluate whether copper lowering therapy with tetrathiomolybdate (TM) affected blood sugar levels in three rodent models of diabetes, streptozotocin (STZ) treated rats and mice, and the db/db mouse model. STZ was administered to rats and mice, and blood sugar levels were followed over a protracted time in these and non-STZ control animals. TM was administered by oral gavage (rats) or in the drinking water (mice) to a portion of the rats and mice to observe effects on blood sugar. Mice with genetically determined diabetes (db/db) were studied by giving half the mice TM in the drinking water and following blood sugar. The results show that TM caused a significant reduction in blood glucose in both STZ treated rats and mice, but no effect on blood glucose in db/db mice. However, TM caused a significant reduction in proteinuria in db/db animals. The results are discussed around the likelihood that TM is inhibiting ongoing inflammatory damage in the pancreas from STZ. A metabolic effect of TM on blood glucose is possible but seems less likely. TM is also likely inhibiting inflammatory and/or fibrogenic effects in the kidneys of db/db mice.

Key Words: diabetes • tetrathiomolybdate • copper • streptozotocin