Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus.
Diabetic neuropathy is associated with some early defects of axonal transport in experimental animals. Axonal transport is dependent on intact microtubules, and unsubstituted lysine residues of tubulin are essential for microtubule polymerization. As lysine residues are the major target for the non-enzymatic attachment of glucose, the effect of diabetes on the extent of glycation of tubulin was investigated. There was a more than four-fold increase in the extent of glycation of tubulin in the sciatic nerve of rats with streptozotocin-induced diabetes of 2 weeks duration compared with control rats. In contrast, no such increase in glycation was observed in brain microtubule protein from diabetic rats at that stage of diabetes. Incubation of brain microtubule protein with glucose prior to in vitro polymerization showed that the early stages of glycation were not associated with inhibition of microtubule assembly. The observed glycation of peripheral nerve tubulin in early experimental diabetes may nevertheless contribute to axonal transport abnormalities through an as yet undetermined impairment of microtubule function.
Cullum
N A
NA
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Mahon
J
J
Stringer
K
K
McLean
W G
WG
D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D001921:Brain / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006031:Glycosylation; D008239:Lysine / Q000378:metabolism; D008868:Microtubule Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism* / Q000502:physiology; D013311:Streptozocin; D014404:Tubulin / Q000378:metabolism*
D008868:Microtubule Proteins; D014404:Tubulin; D013311:Streptozocin; D008239:Lysine