Effects of thyroid hormone on the sorbitol pathway in streptozotocin-induced diabetic rats

Sorbitol accumulation plays an important role in diabetic complications inv olving the kidney, nerves, retina, lens and cardiac muscle. To investigate the influence of thyroid hormone on the sorbitol pathway, we studied the ef fects of thyroid hormone on polyol metabolism in normal and diabetic rats. Rats were divided into three groups: controls, streptozotocin (STZ)-induced diabetic euthyroid rats (DM) and STZ-induced diabetic hyperthyroid (thyrox ine-injected) rats (DM+HT). The sorbitol (Sor) concentrations in the kidney , liver and sciatic nerve (2.53 +/- 0.74, 0.97 +/- 0.16 and 24.0 +/- 5.1 nm ol/mg protein, respectively) of the DM rats were significantly higher than those (1.48 +/- 0.31, 0.58 +/- 0.13 and 3.1 +/- 0.6 nmol/mg protein) of the control rats. The Sor concentrations in the kidney and sciatic nerve of th e DM+HT rats (1.26 +/- 0.29 and 9.40 +/- 1.2 nmol/mg protein) were signific antly lower than those in the DM rats. These values were reduced in the liv er, unchanged in the kidney, and increased in the sciatic nerve from the hy perthyroid rats without diabetes. Thyroid hormone reduced the aldose reduct ase (AR) activities in the kidney, liver and sciatic nerve of the DM rats, and similarly reduced AR in the kidney and liver, but not in the sciatic ne rve, of the non-diabetic rats. The sorbitol dehydrogenase (SDH) activities were decreased by thyroid hormone in the kidney and liver but not the sciat ic nerve of DM rats. In the non-diabetic rats, this enzyme activity was dec reased in liver, but not in kidney or sciatic nerve. A positive correlation between the Sor concentration and AR activity was observed in the kidney a nd liver but not in the sciatic nerve from control, DM and DM+HT rats. A ne gative correlation was observed between the Sor concentration and SDH activ ities in the same organs. These data suggest that thyroid hormone affects t he sorbitol pathway, but the detailed mechanism whereby this hormone reduce s the sorbitol content (especially in diabetic rats) remains to be clarifie d. (C) 1998 Published by Elsevier Science B.V. All rights reserved.