Diabetes-related alterations in the enteric nervous system and its microenvironment

Abstract

Gastric intestinal symptoms common among diabetic patients are often caused by intestinal motility abnormalities related to enteric neuropathy. It has recently been demonstrated that the nitrergic subpopulation of myenteric neurons are especially susceptible to the development of diabetic neuropathy. Additionally, different susceptibility of nitrergic neurons located in different intestinal segments to diabetic damage and their different levels of responsiveness to insulin treatment have been revealed. These findings indicate the importance of the neuronal microenvironment in the pathogenesis of diabetic nitrergic neuropathy. The main focus of this review therefore was to summarize recent advances related to the diabetes-related selective nitrergic neuropathy and associated motility disturbances. Special attention was given to the findings on capillary endothelium and enteric glial cells. Growing evidence indicates that capillary endothelium adjacent to the myenteric ganglia and enteric glial cells surrounding them are determinative in establishing the ganglionic microenvironment. Additionally, recent advances in the development of new strategies to improve glycemic control in type 1 and type 2 diabetes mellitus are also considered in this review. Finally, looking to the future, the recent and promising results of metagenomics for the characterization of the gut microbiome in health and disease such as diabetes are highlighted.

Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis

“…The TNBS-induced increase in nNOS-IR neurons in the inflamed colon is consistent with previous findings (11). Furthermore, changes in the size and distribution of nNOS neurons have been associated with oxidative stress (5). MSC and CM treatment counteracted morphological changes and inflammationinduced increases in the quantity and proportion of nNOS-IR neurons.…”

High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon

“…HFD impairs neurogenic SM relaxation in WT but not in BK␤ 1 Ϫ/Ϫ mice. We measured neurogenic circular muscle relaxations to test if smaller IJPs are associated with changes in neurogenic relaxations (Fig.…”

“…Furthermore, we propose that these changes contribute to impaired inhibitory neuromuscular transmission and increased SMC excitability. We tested our hypothesis using colonic tissues from wild-type (WT) and BK␤ 1 Ϫ/Ϫ mice fed a control diet (CD) or a HFD. We found that mice fed a HFD exhibited myenteric plexus oxidative stress, fewer myenteric nitrergic neurons, reduced inhibitory neuromuscular transmission, increased SMC excitability, and impaired colonic motility.…”

Building a second brain in the bowel

“…In IBS, altered bowel motility and sensory responses cause pain accompanied by diarrhea or constipation, but health is not otherwise affected. ENS defects also occur in Parkinson's disease (8), diabetes (9), and inflammatory bowel disease (IBD) (10), and recent data suggest that ENS damage might play an early etiologic role in IBD (11,12) and Parkinson's disease (13)(14)(15). Here, we focus on cellular and molecular mechanisms controlling ENS development, highlighting areas that require further investigation and potential clinical implications of new discoveries.…”