After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean ± SE 30.9 ± 0.6 vs. 41.4 ± 1.8 m/s, P < 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 ± 0.9 m/s, P < 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 ± 0.23 ng/g wet wt) compared with the other groups (control, 3.10 ± 0.44, P < 0.01; insulin-treated STZ-D, 2.44 ± 0.55, P < 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P < 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = −0.5624, P < 0.001). NCV was also inversely correlated with blood glucose levels (r = −0.7662, P < 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy.

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