Reversibility and Preventability of the Decrease in Slow Axonal Transport Velocity in Experimental Diabetes

Publisher Website
Google Scholar
Abstract
The effect of insulin treatment on the slow axonal transport velocity of sciatic nerve was examined in streptozotocin-diabetic rats following the injection of 3H-proline into the fifth lumbar spinal ganglion. Strict insulin treatment, started immediately after the induction of diabetes and continued until the end of the experiment (group 1), can prevent the slowing in transport occurring in untreated diabetic rats [controls 0.98 ± 0.06 mm/day (mean ± SD); untreated diabetic rats 0.83 ± 0.10 mm/day; insulin-treated rats 1.00 ± 0.11 mm/day]. Strict insulin treatment when postponed for 3 wk (group 2), also can reverse an already slowed transport velocity (0.94 ± 0.05 mm/day). In addition, the influence on the transport abnormality of diabetes was studied in a situation where proteins were synthesized during normoglycemia and already in transport at the time of administration of streptozotocin; i.e., 2 days following protein labeling. The mean velocities were identical in rats made diabetic prior to (group 1) or following (group 2) protein labeling (0.83 ± 0.10 m/day and 0.83 ± 0.06 mm/day, respectively), Indicating that the metabolic derangement leads to a decrease in transport all along the axon as soon as the state is induced. The percentage of TCA-insoluble label in slow component a (SCa) of the transport system was decreased in the three groups with elevated glucose level at the time of pulse-labeling (untreated group 1: 16.9 ± 8.3%; insulin-treated group 1 and 2:11.8 ± 8.1% and 10.3 ± 6.3%, respectively) as compared with rats with normoglycemia (controls: 27.4 ± 13.9% and untreated group 2: 35.1 ± 10.0%). Thus a normal metabolic state at the time of pulselabeling followed by induction of hyperglycemia (diabetes group 2) results in decreased transport velocity of a normal amount of label, whereas the opposite metabolic situation (insulin-treated groups) leads to a normal transport velocity of a decreased amount of protein. We suggest that SCa is propelled by the continuous delivery of protein from the nerve cell body and, consequently, that the decreased amount of label in SCa as well as its slowed advancement indicate a defect in protein synthesis or in allocation of protein in the cell bodies.

This publication has 0 references indexed in Scilit: