Changes in Uridine Nucleotides and Uridine Nucleotide Sugars in Diabetic Rat Lens: Implications in Membrane Glycoprotein Formation

The lens has a very high content of UDP sugars. These are required for glycoprotein and proteoglycan synthesis, as components of fiber cell membranes and the capsule. In diabetes, changes in these sugar nucleotides are related to pathological changes in the basement membranes of cells from non-insulin-requiring tissues. We have investigated whether this is the case in the lens in diabetes and we report here that UDP-sugar levels are, in contrast to the norm in other non-insulin-requiring tissues, decreased at 2 and 4 weeks of diabetes. This is despite an elevation in the precursors of their formation, both of the pyrimidine (PPRibP) and carbohydrate (glucose, glucose 6-phosphate) components. Also reported here is the observation that lens pyrimidine biosynthesis occurs primarily by the de novo route, and that orotate phosphoribosyltransferase and orotidine-5′-phosphate decarboxylase are unchanged in diabetes. We have measured the energy charge of the adenine and uridine nucleotide pools and report both to be compromised under the diabetic condition. The fall in ATP provision is proposed to be responsible for the fall in UTP and hence leads to the recorded decrease in the UDP sugars. These changes are discussed in relation to the change in capsular and fiber cell composition and the functional significance of this in cataract formation.