Insulin modulates duodenal vagal afferents basal activity

Hyperglycemia markedly modifies gastro-duodenal motility. The question was raised whether hyperinsulinaemia, which is usually concomitant to hyperglycemia, could be the factor responsible for this effect through alteration of gastro-duodenal sensitivity. Indeed, vagal receptors are directly activated by insulin in lambs. However, insulin action significantly differs in ruminants and non-ruminants. The aim of our study was therefore to check (i) if insulin per se was able to modulate basal and distension induced discharges of duodenal vagal afferents in a monogatric animal model and (ii) if its action was direct or indirect through changes in gut compliance. Fourteen duodenal mechanoreceptors were studied in anaesthetized curarized pigs using the “single-fiber” method performed on the left cervical vagus. The characteristics of the vagal receptors were studied before (Control), and after (i) local insulin infusion in the gastroepiploic artery (IA), (ii) IV insulin perfusion inducing systemic hypoglycemia (IV), and (iii) during an euglycemic hyperinsulinemic clamp (EH). Basal recording, isobaric and isovolumetric distensions were performed in all experimental conditions. Basal discharge was significantly increased during IA (5.8 ± 0.28 spikes/5 s), IV (6.6 ± 0.30 spikes/5 s) and EH (5.7 ± 0.25 spikes/5 s) compared to Control (4.4 ± 0.27 spikes/5 s, p < 0.05). Responses during isobaric and isovolumetric distensions were identical irrespective of the experimental condition. Gut compliance and intraluminal pressure during basal recording were not modified (p > 0.05). In conclusion, insulin increased duodenal vagal mechanoreceptors basal activity but did not modulate the mechanosensitivity of the vagal units. Insulin-induced increase in basal discharge rate was due to hyperinsulinemia per se since it persisted during the euglycemic hyperinsulinemic clamp.