Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.

Proceedings of the National Academy of Sciences of the United States of America

PubMedID: 6959136

Williams SK, Howarth NL, Devenny JJ, Bitensky MW. Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus. Proc Natl Acad Sci USA. 1982;79(21):6546-50.
The extent of in vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTP-dependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.