Duration-dependent changes in calcium responsiveness in the alloxan-diabetic rat intestine

Disturbances of the gastrointestinal tract that are common in diabetes mellitus seem to be related to intestinal motility. In experimental models of diabetes, decreased calcium sensitivity has been demonstrated in various smooth muscles including those in the gastrointestinal tract. The main purpose of the present study was to examine further the calcium sensitivity in diabetic rat intestine and to understand if changes in the calcium sensitivity occur at an earlier stage of the disease. For this purpose, the effects of potassium and calcium were evaluated on nondepolarized and depolarized duodenum from rats with alloxan diabetes for 1 and 8 weeks and their age-matched controls. To evaluate the calcium sensitivity in rat duodenum, apparent affinity constants (pD2 values) and intrinsic activities (alpha E values) were calculated for every experimental conditions examined in this study. Both values (pD2 and alpha E) for the effects of potassium and calcium on the nondepolarized and depolarized duodenum, respectively, were not changed in 1-week diabetic rats. In contrast, intrinsic activities for the effects of potassium and calcium were found to be significantly decreased (p < 0.001) in the nondepolarized and depolarized duodenum from rats with alloxan diabetes for 8 weeks, whereas apparent affinity constants were not altered in this case. Taking into consideration all these experimental findings, the decreased calcium sensitivity in gastrointestinal tract seems to be closely related to decreased calmodulin levels and may occur at a later stage of diabetes as a linkage to long-term gastrointestinal complications.