Peripheral nerve pathology in rats with streptozotocin-induced insulinoma

Peripheral nerve structure was systematically examined in rats with insulinoma induced by streptozotocin (STZ). Normal Wistar rats, aged 3 months (n = 10), were treated with intravenous injections of STZ (20 mg/kg) and housed in plastic cages with free access to water and chow until 24 months of age. Three rats with insulinoma survived and were examined pathologically. Age-matched normal Wistar rats (n = 6) were used for comparison. The insulinoma-bearing rats showed a marked increase in body weight and decrease in blood glucose. In a teased nerve fiber study of the sciatic nerve, the percentage of abnormal fibers undergoing axonal degeneration and de- and remyelination in age-matched normal control rats was 3.9 +/- 2.5% (means +/- SD), whereas in the three insulinoma-bearing rats 49%, 50%, and 24%, respectively, of the fibers showed such changes. Regenerating fibers were also numerous in each insulinoma-bearing rat (36%, 42% and 27%, respectively). Morphometric analysis revealed smaller mean myelinated fiber and axonal areas in all the nerves examined (sciatic, tibial and sural) in insulinoma-bearing rats as compared to those in age-matched normal rats. Fiber area frequency histograms showed a decrease in large myelinated fibers and an increase in small regenerated fibers in insulinoma-bearing rats. Ultrastructurally, endoneurial microvessels exhibited a narrowed vascular lumen with swollen endothelial cells and vacuolar degeneration of pericytes, suggesting an involvement of vascular changes in the neuropathic development. The present study demonstrated marked structural changes in both motor and sensory peripheral nerves of rats bearing experimentally induced insulinoma. We consider that axonal degeneration, regeneration and demyelination constitute the main pathology in the peripheral nerves of insulinoma-bearing rats, although no particular difference in severity of the lesions between sensory and motor and between proximal and distal nerves was apparent.