Abstract
Hyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO), at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. However, hyperglycemia has also been reported to cause fast gastric emptying that may be due to suppression of the inhibitory motor neurons. The purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia. Inhibitory electrical junction potentials were recorded from gastric antral muscle strips, using intracellular electrodes under non-adrenergic, non-cholinergic conditions. Studies were performed in non-hyperglycemic NOD (NH-NOD), NOD mice as they develop hyperglycemia (H-NOD) and their age-matched controls. The purinergic inhibitory junction potential (pIJP) and nitrergic IJP (nIJP) were isolated pharmacologically. The control pIJP was large, around -18 mV and nIJP was small, around -9 mV. In NH-NOD the IJPs were not affected, but in H-NOD pIJP was nearly abolished and nIJP was significantly reduced. In H-NOD mice, membrane hyperpolarization caused by exogenous α,β-MeATP or diethylenetriamine NO adduct was similar to that in wild-type controls (P > 0.05). H-NOD smooth muscles were significantly depolarized as compared to NH-NOD smooth muscles. These observations show that hyperglycemia causes suppression of purinergic and nitrergic transmission by acting on the motor neurons that form the last neuron in the vagovagal circuit. Moreover, the loss the neurotransmission is due to a defect in neurotransmitter release rather than a defect in signal transduction. Hyperglycemia also causes depolarization of smooth muscles that may increase their excitability.
Highlights
Vagus nerve and myenteric plexus play a central role in the regulation of gastric motility and gastric emptying [1]
Fast gastric emptying is increasingly recognized as a complication of early diabetes and hyperglycemia in animal models of diabetes including NOD mice [16], leprdb/db mice [18] and streptozotocin-induced diabetes mellitus [17]
In one study of diabetic patients who underwent gastric emptying studies for clinical symptoms, fast gastric emptying was found to be fast in 22%, normal in 42%; and slow in 36% of the cases [29]
Summary
Vagus nerve and myenteric plexus play a central role in the regulation of gastric motility and gastric emptying [1]. The neural circuits that mediate vagovagal reflexes include vagal afferents with their cell bodies located in the nodose ganglion and their centrally projecting fibers found in the nucleus tractus solitarius, that synapse on neurons in the dorsal motor nucleus of the vagus (DMV). The myenteric plexus mediates local intragastric reflexes that integrate activities of different parts of the stomach that is required for gastric motility and gastric emptying. The vagal postganglionic/myenteric inhibitory and excitatory neurons are final components of the vagovagal or local myenteric plexus circuits. Hyperglycemia has been reported to enhance vagovagal reflex that causes the release of inhibitory neurotransmitter, nitric oxide (NO), at the neuromuscular junction in the antrum to relax the antrum and slow gastric emptying by stimulating glucose-sensitive afferent neurons. Aims: The purpose of the present study was to investigate changes in inhibitory neuromuscular transmission in the gastric antrum due to hyperglycemia
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