Biomechanical and Histomorphometric Colon Remodelling in STZ-Induced Diabetic Rats

Abstract

The histomorphologic and passive biomechanical properties were studied in the mid-colon of 16 non-diabetic and 20 streptozotocin (STZ)-induced diabetic rats (50 mg/kg STZ, ip). The diabetic rats were divided into groups living 4 and 8 weeks after the induction of diabetes (n = 10 for each group). The mechanical test was a ramp distension of fluid into the colon in vitro. The colon diameter and length were obtained from digitized images of the segments at pre-selected pressures and at the no-load and zero-stress states. Circumferential and longitudinal stresses and strains were computed from the length, diameter, and pressure data and from the zero-stress state geometry. The blood glucose level increased 3-4-fold in the diabetic rats compared with the controls (P < 0.001). Diabetes generated pronounced increases in the colon weight per length, wall thickness, and wall cross-sectional area (P < 0.001). Histologically, the thickness of all layers was increased during diabetes (P < 0.05), especially the mucosa layer. The opening angle, and absolute values of residual strain increased in the diabetic group (P < 0.05 and P < 0.01, respectively). Furthermore, diabetes increased the circumferential and longitudinal stiffness of the colon wall (P < 0.001). The observed changes in residual strain, opening angle, and stress-strain relation may be contributing factors to colonic dysfunction and abdominal pain in diabetic patients.

Advanced glycation end-product expression is upregulated in the gastrointestinal tract of type 2 diabetic rats

“…The pathogenesis of such symptoms in diabetes mellitus is complex, multi-factorial with motor dysfunction, glycemic control, autonomic neuropathy, and psychological factors, and is not well understood [4] . Previous studies demonstrated changes in the morphological and biomechanical properties of the GI tract during diabetes, e.g., the wall thickness and stiffness of GI tract increased [5][6][7] . The structure or deformation changes may alter the relative positions of the mechanosensitive afferents (zero setting of the mechanosensitive afferents).…”

“…For example the esophagus and colon were morphologically and biomechanically remodeled during the development of diabetes [6,7] . Abnormal levels of AGE and RAGE found in the present study may be associated with the GI remodeling in the GK diabetic rats.…”

Diabetes-induced mechanophysiological changes in the small intestine and colon

“…Many animal and human studies have demonstrated that DM generally induces changes in the proliferation of different layers[5,8,10,41-51]. Increased expression of advanced glycation end of product (AGE) and AGE receptor (RAGE) has been demonstrated in the DM intestinal and colonic wall[49,51,52].…”

“…However, data on biomechanical changes in the diabetic colon is sparse. We have also investigated DM-induced biomechanical and morphometric remodeling in rat colon[10]. It was found in diabetic colon that the opening angle and residual strain became bigger and the stiffness of the colon wall increased with the duration of DM both in the circumferential and longitudinal directions (Figure 2).…”

“…Furthermore, it has been recently recognized that DAN also includes the disorders of the enteric nervous system (ENS)[7]. It is well known that DM induces histomorphological and biomechanical remodeling of small intestine and colon in type-1 DM patients[5] and in DM animals[8-10]. Such remodeling is closely related to motor-sensory dysfunctions in DM patients[9].…”