Islet amyloid polypeptide and calcitonin gene-related peptide expression are down-regulated in dorsal root ganglia...

Islet amyloid polypeptide (IAPP) is structurally related to calcitonin gene-related peptide (CGRP) and has been implicated in glucose homeostasis and diabetes pathogenesis because it is expressed in insulin cells and forms amyloid in pancreatic islets from type II diabetic patients. IAPP is also constitutively co-expressed with CGRP in rat sensory neurons. Whether expression of IAPP is altered by nerve injury with or without regeneration was investigated in adult rats subjected to unilateral sciatic axotomy; IAPP and CGRP expression were determined by quantitative in situ hybridization and immunocytochemistry at days 3, 10 and 30 after axotomy. In ipsilateral L4-L5 dorsal root ganglia (DRG), the percentages of nerve cell profiles labelled for IAPP and CGRP mRNA were reduced at all time points studied. IAPP and CGRP mRNA expression were lower in nerve cell profiles in ipsilateral DRGs compared to the contralateral side after axotomy alone whereas epineurial nerve suture maintained or restored IAPP and CGRP expression. The numbers of IAPP- and CGRP-immunoreactive DRG nerve cell profiles and dorsal horn fibers were reduced on the ipsilateral side at all time points. Thus, IAPP and CGRP expression are down-regulated upon axotomy. Nerve repair maintains or restores IAPP and CGRP expression in individual neurons but does not prevent the loss of CGRP/IAPP phenotype of some of these neurons in response to axotomy.