Effect of diabetes on the sugar nucleotides in several tissues of the rat.

Studies have been carried out to determine the effect of diabetes on the concentrations of sugar nucleotides in several tissues of the rat. This represents one aspect of an investigation aimed at evaluating the role which alterations in the metabolism of glycoproteins or other glycoconjugates may play in the development of the long-term complications of this disease. Measurements were made of the nucleotides of hexoses, N-acetylhexosamines, hexuronic acids, and sialic acid in liver, kidney, skeletal muscle, testis and heart of alloxan-diabetic rats and age-matched controls. Of the intermediates studied, only UDP-glucose and UDP-galactose showed significant alterations in diabetes. The direction of the changes depended on the tissue, with the levels in liver and skeletal muscle being decreased, those in kidney and testis increased and the concentrations in heart being unchanged. In the diabetic liver, the concentrations of UDP-glucose was reduced to 0.75 that of normal, while in skeletal muscle both UDP-glucose and UDP-galactose were significantly decreased (diabetic to normal ratios of 0.67 and 0.64, respectively). Kidney and testis, on the other hand, showed elevations of both UDP-glucose and UDP-galactose, with the diabetic levels being 1.2 to 1.3 those of normal levels. The direction of change in UDP-glucose in a tissue appeared to reflect its known ability to synthesize glycogen in diabetes. The finding of elevated UDP-glucose and UDP-galactose concentrations in diabetic kidney is considered to be potentially of great importance to the increased synthesis of basement membrane collagen by this tissue.