Immediate Insulin Treatment Prevents Diabetes-Induced Gut Region-Specific Increase in the Number of Myenteric Serotonergic Neurons

Diána Mezei,János Balázs,Mária Bagyánszki,Zita Szalai,Zsuzsanna Márton,Nikolett Bódi

doi:10.3390/app11135949

Abstract

To evaluate the effects of hyperglycemia and insulin treatment on the proportion of serotonin-immunoreactive (5-HT-IR) myenteric neurons, samples were taken from the duodenum, ileum, and colon of diabetic, insulin-treated diabetic, and control rats 10 weeks after the onset of streptozotocin-induced hyperglycemia. Myenteric whole-mount preparations were immunostained with anti-5-HT and pan-neuronal anti-HuCD markers. In controls, the 5-HT-IR myenteric neurons represent a small proportion (~2.5%) of the total neuronal number in the investigated gut segments. The proportion of 5-HT-IR myenteric neurons was significantly higher in the duodenum (p < 0.01) and colon (p < 0.0001) of diabetic rats compared to the controls but exhibited a slight increase in the ileum. Immediate insulin treatment resulted in a significantly lower proportion of myenteric 5-HT-IR neurons in each segment (duodenum p < 0.0001; ileum p < 0.01; and colon p < 0.0001) compared to the untreated diabetics. Our study demonstrates that the proportion of 5-HT-IR myenteric neurons was enhanced in type 1 diabetes in a region-specific manner. Immediate insulin treatment prevents a higher hyperglycemia-induced amount of 5-HT-IR neurons and restores it to the control level in each investigated gut segment. Despite the low proportion of 5-HT-IR myenteric neurons, hyperglycemia-related changes of these neurons may play a crucial role in gastrointestinal symptoms in type 1 diabetes.

Highlights

Diabetic patients often suffer from gastrointestinal (GI) symptoms such as nausea, vomiting, diarrhea, constipation, dyspepsia, or abdominal pain
The occurrence of 5-HT-IR myenteric neurons was calculated as the proportion of the total myenteric neuronal number that was HuCD-stained
Based on our earlier findings [33,34] regarding changes in the total neuronal number in diabetes, on present results of percentage of myenteric ganglia containing 5-HT-IR neurons, and the total number of serotonergic neurons in these ganglia, we presume that the increase in the percentage of 5-HT-IR neurons relative to the total neuronal number in the duodenum was due to neurochemical alterations of myenteric neurons

Summary

Introduction

Diabetic patients often suffer from gastrointestinal (GI) symptoms such as nausea, vomiting, diarrhea, constipation, dyspepsia, or abdominal pain. These complications are associated with structural and functional alterations of the enteric nervous system (ENS), which is known as diabetic enteropathy [1]. The myenteric plexus is located between the circular and the longitudinal muscle layers of the gut wall and regulates intestinal motility [2]. The submucous neurons influence mucosal secretion, electrolyte absorption across the mucosa, blood flow, and intestinal motility [3,4,5,6]

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