Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract.

Katarzyna Palus,Michał Bulc,Łukasz Zielonka,Jarosław Całka,Marcin Nowicki

doi:10.3390/ijms22115727

Abstract

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.

Highlights

Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action and is one of the most commonly encountered endocrinopathies worldwide
An increased number of pituitary adenylate cyclase-activating polypeptide (PACAP)-like immunoreactive (LI) neurons in Myenteric plexus (MP) observed in the present study suggests that PACAP may be involved in the control of motor function of the small intestines and the descending colon in the course of diabetes
Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon

Summary

Introduction

Diabetes mellitus (DM) is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action (or both) and is one of the most commonly encountered endocrinopathies worldwide. The International Diabetes Federation (IDF) reports that there were 424 million cases of diabetes in 2017. It is estimated that the number of cases in 2040 will increase significantly and will amount to 642 million [1]. Previous studies have shown that hyperglycaemia evokes chronic complications by vascular endothelium damage, inflammatory conditions and several organic dysfunctions [2]. Diabetic gastroenteropathy is a common complication that develops in patients with long-term diabetes. Clinical symptoms including abdominal pain, vomiting, heartburn, diarrhoea and obstipation have been confirmed in diabetic patients, especially in poorly controlled glycaemia [2,3]. Gastroenteropathy contributes to lowering the quality of life and hinders proper glycaemic control, knowledge of its pathophysiology

Methods

Discussion

Conclusion