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, 19 (2), 161-70

Gastrointestinal Motility Changes and Myenteric Plexus Alterations in Spontaneously Diabetic Biobreeding Rats

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Gastrointestinal Motility Changes and Myenteric Plexus Alterations in Spontaneously Diabetic Biobreeding Rats

Ingrid Demedts et al. J Neurogastroenterol Motil.

Abstract

Background/aims: Type 1 diabetes is often accompanied by gastrointestinal motility disturbances. Vagal neuropathy, hyperglycemia, and alterations in the myenteric plexus have been proposed as underlying mechanism. We therefore studied the relationship between vagal function, gastrointestinal motiliy and characteristics of the enteric nervous system in the biobreeding (BB) rat known as model for spontaneous type 1 diabetes.

Methods: Gastric emptying breath test, small intestinal electromyography, relative risk-interval variability, histology and immunohistochemistry on antral and jejunal segments were performed at 1, 8 and 16 weeks after diabetes onset and on age-matched controls.

Results: We observed no consistent changes in relative risk-interval variability and gastric emptying rate. There was however, a loss of phases 3 with longer duration of diabetes on small intestinal electromyography. We found a progressive decrease of nitrergic neurons in the myenteric plexus of antrum and jejunum, while numbers of cholinergic nerve were not altered. In addition, a transient inflammatory infiltrate in jejunal wall was found in spontaneous diabetic BB rats at 8 weeks of diabetes.

Conclusions: In diabetic BB rats, altered small intestinal motor control associated with a loss of myenteric nitric oxide synthase expression occurs, which does not depend on hyperglycemia or vagal dysfunction, and which is preceded by transient intestinal inflammation.

Keywords: Diabetes mellitus; Electromyography; Enteric nervous system; Gastric empyting; Rats, inbred BB.

Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1
Figure 1
Gastric half emptying times for semi-solids in diabetic and sex- and age-matched control rats at 1, 8 and 16 weeks after onset of diabetes. No significant differences occurred between both groups at any time point.
Figure 2
Figure 2
(A) Example of semi-automatic analysis of small intestinal electromyography of 2 consecutive electrodes (E1 and E2). Activity fronts (▪) are defined as periods of at least 1 minute, in which the integrated signal is raised above the set threshold. (B) Number of phases 3 per hour in diabetic and sex- and age-matched control rats at 1, 8 and 16 weeks after onset of diabetes. Over time, the number of phases 3 decreased significantly in the diabetic group.
Figure 3
Figure 3
Representative image of 8 and 16 weeks diabetic rat by H&E staining. Eight weeks after onset of diabetes, infiltration of polymorphonuclear leukocyte cells into enteric nervous system (SP, submucosal plexus; MP, myenteric plexus) was present with thickening of the muscular layers (CM, circular muscle; LM, longitudinal muscle). However, 16 weeks after onset of diabetes, no inflammatory infiltrate was seen. Scale bar = 50 µm.
Figure 4
Figure 4
Number of nitrergic (neuronal nitric oxide synthase-immunoreactive [nNOS-IR]) neurons per ganglion in the antrum (A) and jejunum (B) in diabetic and sex- and age-matched control rats at 1, 8 and 16 weeks after onset of diabetes. Over time, antral nNOS-IR decreased significantly in both groups. Counts of nNOS myenteric neurons were lower in diabetic than in control animals at every time point. In the myenteric plexus of the jejunum, nNOS-IR decreased significantly over time in both diabetic and control animals. In diabetic animals, nNOS-IR was significantly decreased at week 8 and 16 compared with control. *P < 0.001, **P < 0.01, ***P < 0.05, ****P = 0.05 compared with control at each time points. (C) Representative image of nNOS-IR neurons in 8 week diabetic rat. Scale bar = 100 µm.

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