Diabetes and the enteric nervous system

Abstract

Diabetes is associated with several changes in gastrointestinal (GI) motility and associated symptoms such as nausea, bloating, abdominal pain, diarrhoea and constipation. The pathogenesis of altered GI functions in diabetes is multifactorial and the role of the enteric nervous system (ENS) in this respect has gained significant importance. In this review, we summarize the research carried out on diabetes-related changes in the ENS. Changes in the inhibitory and excitatory enteric neurons are described highlighting the role of loss of inhibitory neurons in early diabetic enteric neuropathy. The functional consequences of these neuronal changes result in altered gastric emptying, diarrhoea or constipation. Diabetes can also affect GI motility through changes in intestinal smooth muscle or alterations in extrinsic neuronal control. Hyperglycaemia and oxidative stress play an important role in the pathophysiology of these ENS changes. Antioxidants to prevent or treat diabetic GI motility problems have therapeutic potential. Recent research on the nerve-immune interactions demonstrates inflammation-associated neurodegeneration which can lead to motility related problems in diabetes.

Figure 1

Schematic representation of the central role of enteric neuropeptides in diabetes: diabetes leads to an imbalance of inhibitory and excitatory neuropeptide ratios which can directly cause altered gut motility. In addition, hyperglycaemia can also cause oxidative stress and apoptosis. Other potential mechanisms involve the role of neuropeptides from enteric nervous system (ENS) interacting with immune cells and activating pro-inflammatory cytokine production leading to inflammation and subsequent neuronal loss. Thus oxidative stress, apoptosis and inflammation cause nerve damage leading to gastrointestinal motility disturbances.