Entero-pancreatic neurons are responsible for the intestinal phase of pre absorptive insulin secretion

Insulin is a key hormone of the intermediary metabolism and its early secretion after a meal has a major role in the overall organism glucose sensitivity. Pre absorptive insulin secretion (PAIS) includes a cephalic phase (implicating oro-pharyngeal receptors) and an intestinal phase (implicating gastric and duodenal receptors). Entero-pancreatic (EP) neurons, which originate from the antral and the proximal duodenal intrinsic nervous systems, form varicosities in pancreatic ganglia and islets and may account for the intestinal phase of PAIS. To test this hypothesis, post prandial portal insulin and arterial glucose concentrations were compared in (i) intact pigs (IEP), (ii) pigs with gastric canula, (IEP+GC) and (iii) pigs with gastric canula and surgically interrupted EP neurons (XEP+GC) (n=8). EP neurons section was achieved by sectioning the connective attachments between the pancreas and the proximal duodenum and the antrum. The test meal (800 ml of glucose 5%) was ingested voluntarily (IEP), or directly introduced into the stomach (IEP+GC, XEP+GC), to discriminate between the cephalic and the intestinal phases of PAIS. PAIS was significantly decreased in IEP+GC compared to IEP (AUC=59±21.2 vs 18±6.6 μUI/ml/5 min for IEP vs IEP+GC, p=0.04). PAIS was further nullified in XEP+GC (AUC=−2±8.1 μUI/ml/5 min). Glycemia was not modified in IEP, IEP+GC or XEP+GC. We conclude that EP neurons are responsible for the intestinal phase of PAIS since it disappeared in XEP+GC.