Substance P in the Gastrointestinal Tract of Non-Obese Diabetic Mice

Abstract

Background: Gut dysmotility occurs in most diabetics. Substance P is a neurotransmitter that plays an important role in regulating gastrointestinal motility. The present investigation was carried out to evaluate the possible role of this neurotransmitter in the pathogenesis of dysmotility in diabetics. Methods: Pre-diabetic and diabetic female non-obese diabetic (NOD) mice aged 22-24 weeks were studied. As controls, BALB/CJ mice of the same age and sex were used. Substance P concentrations in tissue extracts from the antrum, duodenum, and colon were determined with radioimmunoassay. Substance P-immunoreactive nerve elements and endocrine cells were identified by immunocytochemistry and quantified with computerized image analysis. Results: Substance P levels in the antrum of both pre-diabetic and diabetic NOD mice were significantly lower than those of controls. In the duodenum and colon substance P levels were higher than those of the controls in both pre-diabetics and diabetic NOD mice. The relative volume density of substance P-immunoreactive nerve fibres in the colon of diabetic NOD mice was significantly decreased. There was no statistically significant difference between pre-diabetic and diabetic NOD mice and controls with regard to the relative volume density of substance P immunoreactive nerve fibres in the antrum and duodenum. In the antrum the number of substance P-immunoreactive cells decreased significantly in both pre-diabetic and diabetic NOD mice. In the duodenum and colon the numbers of these cells in NOD mice did not differ from those of controls. Conclusions: The changes in substance P contents in various parts of the gastrointestinal tract of NOD mice seem to be primary to the onset of diabetes. The decreased antral substance P contents in NOD mice seems to be caused by structural change in the mucosal endocrine cells. In the small and large intestine the increase in substance P levels appears to be caused by change in the physiologic activities of the nerve element and/or endocrine cells rather than by structure changes. The abnormalities observed here in an animal model for diabetes type I might have relevance for the gastrointestinal dysmotility displayed in human diabetes.