Morpho-mechanical intestinal remodeling in type 2 diabetic GK rats--is it related to advanced glycation end product formation?

Abstract

Little is known about the mechanisms for the biomechanical remodeling in diabetes. The histomorphology, passive biomechanical properties and expression of advanced glycation end product (N epsilon-(carboxymethyl) lysine, AGE) and its receptor (RAGE) were studied in jejunal segments from 8 GK diabetic rats (GK group) and 10 age-matched normal rats (Normal group). The mechanical test was done by using a ramp distension of fluid into the jejunal segments in vitro. Circumferential stress and strain were computed from the length, diameter and pressure data and from the zero-stress state geometry. AGE and RAGE were detected by immunohistochemistry staining. Linear regression analysis was done to study association between the glucose level and AGE/RAGE expression with the histomorphometric and biomechanical parameters. The blood glucose level, the jejunal weight per length, wall thickness, wall area and layer thickness significantly increased in the GK group compared with the Normal group (P<0.05, P<0.01 and P<0.001). The opening angle and absolute values of residual strain decreased whereas the circumferential stiffness of the jejunal wall increased in the GK group (P<0.05 and P<0.01). Furthermore, stronger AGE expression in the villi and crypt and RAGE expression in the villi were found in the GK group (P<0.05 and P<0.01). Most histomorphometric and biomechanical changes were associated with blood glucose level and AGE/RAGE expression. In conclusion, histomorphometric and biomechanical remodeling occurred in type 2 diabetic GK rats. The increasing blood glucose level and the increased AGE/RAGE expression were associated with the remodeling, indicating a causal relationship.