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Disorders in gastrointestinal motility associated with morphometric alterations of enteric neurons in experimental models of Diabetes mellitus

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Author(s):
Juliana Fernandes de Matos
Total Authors: 1
Document type: Doctoral Thesis
Press: Botucatu. 2019-04-26.
Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
Defense date:
Advisor: José Ricardo de Arruda Miranda
Abstract

The hyperglycemic state is related to physiological changes throughout the body in diabetes. Recurrence of gastrointestinal disorders in diabetic individuals is known. Studies on changes in gastrointestinal motility in diabetics show damage to enteric neurons and the gastric wall. Few are the knowledge about the relationship among glycemic levels, gastrointestinal motility and enteric neurons. Therefore, the aim was to analyze the activity of contraction, gastric emptying and oro-cecal transit in rats with mild and severe diabetes models and to evaluate the integrity of the gastric wall and the enteric neurons. The animals were diabetic with Streptozotocin (STZ) (moderate diabetes: 100mg/kg; fasting blood glucose 6.6-16.5 mmol/L) and (severe diabetes: 50mg/kg fasting blood glucose>16.5mmol/L). AC biosusceptometry (ACB) measured gastric contractility, quantified per frequency and half-band width in cycles per minute. As well as gastric emptying (EG) and oro-cecal transit, analyzed by mean time of EG and mean time of arrival to the cecum, respectively. Gastric electrical activity was measured by electrogastrogram (EGG). The histology of the gastric wall was performed by hematoxylin-eosin and measured the thickness of the mucosa and the longitudinal and circular muscles of the stomach body. The cholinergic (ChAT) and nitrergic (nNOS) neurons of the myenteric plexus of the stomach body were marked by immunohistochemistry, the density of neurons per ganglion and neural area profile were analyzed. STZ-induced animals had elevated fasting blood glucose and loss of body weight. There was a decrease in the contraction frequency and increase of the band halfwidth, for BAC and EGG, in the diabetes models compared to control. Gastric emptying and oro-cecal transit became slowed in relation to control. The circular muscular layer and mucosa presented thickening in the diabetic groups. ChAT and nNOS neurons showed no difference in neuron density, but neuronal area decreased in diabetics. In conclusion, alterations in motility seems to be associated with changes in the gastric wall and the decrease in the neuronal area of nitrergic and cholinergic neurons that were intensified by long term exposure to hyperglycemic conditions, even that moderate in the diabetes. (AU)

FAPESP's process: 15/05045-8 - Characterization of gastrointestinal motility in diabetes mellitus experimental models: an approach using clamp hyperglycemic and hyperinsulinemic
Grantee:Juliana Fernandes de Matos
Support Opportunities: Scholarships in Brazil - Doctorate