The enhanced spontaneous activity of the diabetic colon is not the consequence of impaired inhibitory control mechanisms.
1. Approximately 45% of patients with diabetes mellitus have gastrointestinal complications such as diarrhoea and constipation, but the underlying aetiology is unclear. The present study investigates alterations in spontaneous motility of the colon that may be, in part, responsible for these symptoms using an established animal model of diabetes. 2. Rats were rendered diabetic by a single intraperitoneal injection of streptozotocin and age-matched controls were injected with citrate buffer. Rats were sacrificed after 8-weeks and proximal colonic circular muscle tissue mounted in organ baths. 3. Spontaneous activity was observed in both control and diabetic tissues, but this activity was almost doubled in colonic tissue taken from diabetic rats. It was hypothesized that this increase was due to a deficit in inhibitory control of the colon in the diabetic state. 4. Possible alterations in nitrergic and vasoactive intestinal polypeptide (VIP)ergic control were investigated using a range of pharmacological tools. 5. Sodium nitroprusside, VIP and antioxidants (reduced glutathione, ascorbate and alpha-tocopherol) inhibited the spontaneous activity, but the level of inhibition observed was not different in diabetic tissue compared with control. 6. Arginine, [D-p-Cl-Phe6, Leu17]-VIP and alpha-chymotrypsin had no effect on spontaneous activity in either sets of tissue. 7. N omega-nitro-L-arginine produced a small, but significant, increase in the level of spontaneous activity, but the degree of increase was not different between control and diabetic tissues. 8. Western blots demonstrated that there was no inducible-nitric oxide synthase (iNOS) in control or diabetic tissues and that the levels of endothelial-NOS (eNOS) and neuronal-NOS (nNOS) detected were not statistically significantly different. The [3H]-citrulline assay established that the functionality of the NOS isoforms present were unaltered in the diabetic state. 9. This study demonstrates that there is a marked alteration in motility in the colon taken from diabetic animals. However, the change in motility is unlikely to be due to a change in inhibitory control mechanisms and may be due to an increased excitability.
Forrest
A
A
Department of Biosciences, Faculty of Natural Sciences, University of Hertfordshire, College Lane, Hatfield, Herts, AL10 9AB, UK.
Parsons
M
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002956:Citrulline / Q000378:metabolism; D003106:Colon / Q000294:innervation / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D000975:Antioxidants; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D009124:Muscle Proteins; D002956:Citrulline; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D009543:Nifedipine