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Am J Physiol Gastrointest Liver Physiol 294: G315-G326, 2008. First published November 15, 2007; doi:10.1152/ajpgi.00196.2007
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NEUROREGULATION AND MOTILITY

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

Abigail Forrest,1 Jan D. Huizinga,2 Xuan-Yu Wang,2 Louis W. C. Liu,2 and Mike Parsons1

1Department of Biosciences, University of Hertfordshire, Hatfield, United Kingdom; and 2Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Submitted 2 May 2007 ; accepted in final form 9 November 2007

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.

diabetes; interstitial cells of Cajal; immunohistochemical staining; rhythmic contractile activity; motility



Address for reprint requests and other correspondence: M. Parsons, Dept. of Biosciences, Univ. of Hertfordshire, College Lane, Hatfield AL10 9AB, UK (e-mail: m.e.parsons{at}herts.ac.uk)







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