Differential effects in CGRPergic, nitrergic, and VIPergic myenteric innervation in diabetic rats supplemented with 2% L-glutamine

Abstract

The objective of this study was to investigate the effects of 2% L-glutamine supplementation on myenteric innervation in the ileum of diabetic rats, grouped as follows: normoglycemic (N); normoglycemic supplemented with L-glutamine (NG); diabetic (D); and diabetic supplemented with L-glutamine (DG). The ileums were subjected to immunohistochemical techniques to localize neurons immunoreactive to HuC/D protein (HuC/D-IR) and neuronal nitric oxide synthase enzyme (nNOS-IR) and to analyze varicosities immunoreactive to vasoactive intestinal polypeptide (VIP-IR) and calcitonin gene-related peptide (CGRP-IR). L-Glutamine in the DG group (i) prevented the increase in the cell body area of nNOS-IR neurons, (ii) prevented the increase in the area of VIP-IR varicosities, (iii) did not prevent the loss of HuC/D-IR and nNOS-IR neurons per ganglion, and (iv) reduced the size of CGRP-IR varicosities. L-Glutamine in the NG group reduced (i) the number of HuC/D-IR and nNOS-IR neurons per ganglion, (ii) the cell body area of nNOS-IR neurons, and (iii) the size of VIP-IR and CGRP-IR varicosities. 2% L-glutamine supplementation exerted differential neuroprotective effects in experimental diabetes neuropathy that depended on the type of neurotransmitter analyzed. However, the effects of this dose of L-glutamine on normoglycemic animals suggests there are additional actions of this beyond its antioxidant capacity.

Enteric glial cell activation protects enteric neurons from damage due to diabetes in part via the promotion of neurotrophic factor release

“…Changing the ratio of inhibitory and contractile neurons can lead to impaired nerve‐mediated muscle responses and contribute to the motility dysfunction seen in diabetes . Our results showed decreased nNOS expression in the ileum 8 and 16 weeks after the induction of diabetes, particularly at 16 weeks, which is consistent with previous reports . Results from previous studies regarding the alterations in cholinergic neurons in diabetes are conflicting, possibly because of the different responses of enteric neuronal subpopulations to hyperglycemia and because the same types of nerves that innervate various regions of the GI tract are affected differently .…”

“…4 Our results showed decreased nNOS expression in the ileum 8 and 16 weeks after the induction of diabetes, particularly at 16 weeks, which is consistent with previous reports. 26,27 Results from previous studies regarding the alterations in cholinergic neurons in diabetes are conflicting, [28][29][30] possibly because of the different responses of enteric neuronal subpopulations to hyperglycemia and because the same types of nerves that innervate various regions of the GI tract are affected differently. 4,28 Our data showed a statistically significant increase in Increasing evidence has confirmed that EGCs are major contributors to the GI complications of diabetes, which provides insight into the role of EGCs in enteric neuropathies.…”

Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway

“…Recent research has revealed that the role of Gln in diabetes goes beyond traditional metabolic functions of amino acids. New discoveries of Gln function have been reported, including the role of enhanced endothelial progenitor cell mobilization in diabetic mice [ 37 ], differential effects in calcitonin gene-related peptide-ergic, nitrergic, and vasoactive intestinal polypeptide-ergic myenteric innervation in diabetic rats [ 38 ], as well as the effect on adhesion molecule expression and oxidative stress in mice with diabetes [ 39 ]. Similarly, our results show that Gln has a beneficial hypoglycemic effect on L6 cells through the PI3K/AKT/GLUT4 signaling pathway, and the hypoglycemic effect of insulin was enhanced in the presence of Gln.…”

Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

“…This lack of effect in this plexus has been previously reported during the development of the diabetic enteric neuropathy [ 33 ]. Another recent study also revealed that l -glutamine exerted a differential neuroprotective effect in experimental diabetes that depend on the type of neurotransmitter analyzed [ 63 ].…”