Association between spontaneous neurogenic atrophy of the femoral muscle and islet cell tumors in aged F344 rats.

In aged F344/DuCrlCrlj rats, we observed that all animals with group atrophy of the biceps femoris muscle also had islet cell tumors, suggesting that spontaneous islet cell tumors may induce peripheral neuropathy and muscle atrophy. Among 220 aged male F344/DuCrlCrlj rats examined, 12.3% (27/220) had islet cell tumors, and of these, 22.2% (6/27) had neurogenic muscular atrophy. Sciatic nerve degeneration was observed in 3.2% (7/220) of cases, and all animals with neurogenic muscular atrophy had sciatic nerve degeneration. Notably, no neurogenic muscular atrophy was observed in rats without islet cell tumors. In contrast, rats with neurogenic muscular atrophy tended to have larger islet cell tumors. Although spinal nerve root degeneration was prevalent (90.8%, 198/218), two of the six rats with neurogenic muscular atrophy did not exhibit this pathology. Immunohistochemically, insulin was positive in all islet cell tumors, although glucagon- and somatostatin-positive reactions showed no association with neurogenic muscular atrophy. Experimentally induced hyperinsulinemia in rats is a known cause of neurogenic muscular atrophy, and similar associations have been reported in humans and spontaneous cases of pet rats with islet cell tumors. A complete coincidence between the occurrence of neurogenic muscular atrophy and islet cell tumors in our investigation suggests that some islet cell tumors in F344/DuCrlCrlj rats may be functionally active, and that hyperinsulinemia may contribute to the pathogenesis of neurogenic muscular atrophy.