World J Diabetes ; 12 5 :May Regionally distinct thickening of endothelial basement membrane BM of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments.
Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9 MMP9 and its tissue inhibitor TIMP1 are essential in regulating extracellular matrix remodelling.
METHODS: Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex- and age-matched control rats.
The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia.
Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tendency for TIMP1 from the proximal to the distal small intestine under control conditions. In the diabetic ileum, the number of MMP9-indicating gold particles decreased in myenteric ganglia, endothelial cells of capillaries and intestinal smooth muscle cells, however, it remained unchanged in all duodenal compartments.