Cyclic nucleotides and cyclic nucleotide phosphodiesterases in kidneys from rats with experimental diabetes

Experimental diabetes was produced in rats by administrations of streptozotocin (STZ) or alloxan (ALX). Some of the diabetic rats were started on daily insulin (NPH) therapy insufficient to control blood glucose. Rats were sacrificed one week or four weeks after confirmation of diabetes along with age-matched control rats. Analyses of cyclic nucleotide levels and of cyclic nucleotide phosphodiesterase activities in samples of kidney cortex revealed the following: cyclic AMP levels and activity of cyclic AMP phosphodiesterase were unaffected in all diabetic animals; cyclic GMP levels and cyclic GMP phosphodiesterase activity were unaffected in STZ-diabetic animals but were altered in ALX-diabetic animals. The data suggest that the altered cyclic GMP levels and degradation was due to a direct nephrotoxic action of ALX that is unrelated to the diabetic state.