Increase in stretch-induced rhythmic motor activity in the diabetic rat colon is associated with loss of ICC of the submuscular plexus

Abstract

Diabetes affects many aspects of gastrointestinal motility, in part due to changes in interstitial cells of Cajal (ICC). The effect of diabetes on the colon, however, is not well characterized, and the aim of the present study was to investigate possible relationships between altered colonic motility as a consequence of streptozotocin-induced diabetes and injury to ICC. Physiological, immunohistochemical, and ultrastructural techniques were employed. The motor pattern of the rat colon was dominated by rhythmic high-amplitude, low-frequency contractions that were primarily myogenic in origin. These rhythmic contractions were induced by stretch associated with increased tension; the amplitude of the superimposed rhythmic contractions increased with increasing applied tension. In diabetic rats, the stretch-induced rhythmic contractile activity remained robust and of similar frequency but was significantly higher in amplitude compared with that in control rats. At 700 mg of applied tension, the force of contraction in circular colonic muscle strips of the diabetic rats was 370% of control values. This robust presence of low-frequency contractions is consistent with the unaffected pacemaker, the ICC associated with Auerbach's plexus, and the increased amplitude correlates with loss of and injury to ICC of the submuscular plexus and intramuscular ICC. Loss of inhibitory nitrergic nerves does not appear to be a factor based on unaltered nNOS immunoreactivity.

Roles of stem cell factor on the depletion of interstitial cells of Cajal in the colon of diabetic mice

“…The morphological examination showed damages in the ultrastructures of the ICC. These findings were in agreement with previous findings in STZ-induced diabetic rats (9). In the previous study, ICC subtypes were examined in the colon of the STZ-induced diabetic rats; both intramuscular ICC and submuscular plexus ICC were scarce, and the area occupied by intramuscular ICC and submuscular plexus ICC was significantly lower compared with the control rats.…”

“…Reduction in the number of ICC has been reported in patients with diabetes (19,27) as well as in animal models of diabetes (9,15,43). The impairment in ICC was reported to be correlated with dysmotility of the gut in diabetic animals (9,43).…”

“…The impairment in ICC was reported to be correlated with dysmotility of the gut in diabetic animals (9,43). In a few recent studies, a loss of SCF was also observed in diabetic animals; one study reported a significant and substantial loss of SCF in the stomach of nonobese diabetic mice (15), and another study reported a reduction of SCF in db/db mice with a mild loss in the stomach but a more significant loss in the distal small intestine and the colon (43).…”

Electroacupuncture at Zusanli (ST-36) Restores Impaired Interstitial Cells of Cajal and Regulates Stem Cell Factor Pathway in the Colon of Diabetic Rats

“…In the current study, Western blot showed an 80% loss of interstitial cells of Cajal in the colon of diabetic rats compared with the control group, which is consistent with previous findings. 19 Our study also found that the expression of c-kit increased significantly in low-and highfrequency-stimulation-treated diabetic rats but was not altered in the sham stimulation group, suggesting that electroacupuncture, both low and high frequency, has the capability to increase the expression of c-kit in diabetic rats. This was consistent with the previous results.…”

Altered calcium signaling in colonic smooth muscle of type 1 diabetic mice

“…Several studies have used streptozotocin (STZ) to cause specific loss of pancreatic ␤-cells creating type 1 diabetes-like animal models. STZ-induced diabetic rats have been reported to exhibit increased small intestine smooth muscle mass and increased colon contractility (10,26). The spontaneous contractile activity in STZ-induced diabetic rat colon smooth muscle was increased (12) without a change in intracellular Ca 2ϩ handling (11), while, in the ileum, intracellular Ca 2ϩ handling was decreased (11).…”