Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.

Seven diabetic Goto-Kakizaki (GK) male rats, 32-wk old (GK group), and 9 age-matched normal Wistar rats (Normal group) were included in the study. Jejunal segments were distended up to a pressure of 10 cm H2O in an organ bath containing 37 °C Krebs solution with addition of carbachol (CA). The pressure and outer diameter changes were synchronously recorded. Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine. Total phasic, tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry. The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.

Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group (mucosa, 755.8 ± 63.3 vs 633.1 ± 59.1 μm, P < 0.01; muscle, 106.3 ± 12.9 vs 85.2 ± 11.7 μm, P < 0.05). The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application (pressure, 1.01 ± 0.07 vs 1.99 ± 0.19 cmH2O, P < 0.01; stress, 0.11 ± 0.01 vs 0.24 ± 0.02 kPa, P < 0.01). CA application did not change the pressure and stress threshold in the Normal group (pressure, 2.13 ± 0.32 vs 2.34 ± 0.32 cm H2O, P > 0.05; stress, 0.25 ± 0.03 vs 0.35 ± 0.06 kPa, P > 0.05). The amplitude of total phasic, total tonic, active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group. However, the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group. When normalized to muscle layer thickness, the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group. No difference was found during CA application.

The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.