Tu2087 Contraction Analysis of Jejunal Segment in Relation to Flow and Ramp Distension in Type 2 Diabetic GK Rats — Responses to Carbachol Stimulation

Abstract

Background and aims: Intestinal motility disorders have been reported in streptozotocin (STZ)-induced diabetic rats. However, STZ can potentially be neurotoxic. Investigating intestinal motility in GK rats which is a genetic model of non-insulin-dependent diabetes avoid the neurotoxic effect. This study was to compare spontaneous, flow-induced and distension-induced contractions with and without carbachol (CA) application in the jejunal segments between normal and diabetic rats. Methods: Seven GK male rats, 32 weeks old (GK group), and 9 age-matched normal Wistar rats (Normal group) were included in the study. The motility experiments were carried out in the organ bath containing Krebs solution at pH 7.4, 37 degree. Before and after CA (10-5 M) application, jejunal pressure and diameter changes were obtained in relation to spontaneous contraction, flow (1 ml/min)-induced contraction with outlet resistance pressures of 0, 2.5, 5.0, 7.5 and 10 cmH2O, and ramp distension up to pressure 10 cmH2O. The frequency and amplitude of contractions were analyzed from pressure-diameter curves. Immediate responses to the CA stimulation were also analyzed. Distension-induced contraction thresholds and maximal contractions of spontaneous and flow-induced contractions in term of mechanical stress and strain were calculated with reference to the zero-stress state. The incremental elastic modulus (IEM) at distensioninduced contraction threshold was also calculated. Results: 1) Shortly after (,10 sec.) adding CA, the contraction amplitude increased immediately to the peak value, then decreased again as function of time. More than two peaks of reaction were observed in GK group but not in Normal group during the 200 seconds observation period. 2) After CA application, the pressure and stress thresholds (Figure 1) and IEM were significantly decreased in the GK group (P,0.01) but not in Normal group (P.0.05). Furthermore, the pressure and stress thresholds were significantly smaller in the GK group compared with Normal group after CA application (P,0.05 and P,0.01). 3) After CA application, the maximum pressure and stress of flow-induced contractions (Figure 2) were significantly higher at most outlet pressure levels in both Normal and GK groups (P,0.001). Furthermore they were significantly bigger at low outlet pressure levels in the GK group than in Normal group after CA application (P,0.05 and P,0.01). 4) The contraction frequency, the strain threshold, and the maximal contraction strain did not differ between the groups (P .0.05) and between before and after CA application (P.0.05). Conclusion: Jejunal contractions in diabetic animals were more sensitive to flow or distension stimulation after CA application. These may relate to tissue remodeling and mechano-sensory changes and contribute to the diabetic symptoms such as diarrhea.