ENTERIC NEUROPEPTIDES IN STREPTOZOTOCIN-DIABETIC RATS - EFFECTS OF INSULIN AND ALDOSE REDUCTASE INHIBITION

The aim of the present study was to determine whether diabetes-induced changes in the distribution of enteric neuropeptides, could be preven ted in 12-week streptozotocin-diabetic rats, by rigorous control of gl ycaemia, using daily adminstration of insulin, or an aldose reductase inhibitor (ponalrestat), The pattern of distribution of nerve fibres a nd cell bodies, containing immunoreactive vasoactive intestinal polype ptide (VIP), galanin (GAL), calcitonin gene-related peptide (CGRP) and substance P was examined in the myenteric plexus of ileum from contro l, untreated diabetic, insulin-treated diabetic and aldose reductase i nhibitor-treated diabetic rats. The increase in VIP- and GAL-like immu noreactivity, seen in the myenteric plexus of untreated diabetic rat i leum, was not present in the myenteric plexus of ileum from insulin- a nd aldose reductase inhibitor-treated diabetic rats. With CGRP-like im munoreactive fibres, there was a clear decrease in the ileum of untrea ted diabetic rats. This was prevented by insulin treatment, but aldose reductase inhibitor treatment had no effect, No alterations in substa nce P-like immunoreactivity were seen in the myenteric plexus of ileum from any of the groups investigated. Generally, the similarity of eff ect of ponalrestat and insulin on VIP and galanin expression in this s tudy supports a primary effect of insulin via glycaemic control, The d issimilarity of the effect of the two treatments on CGRP expression ma y imply a neurotrophic effect of insulin, although there are certainly consequences of hyperglycaemia other than exaggerated flux through th e polyol pathway.