The entero-pancreatic (EP) neurons directly link the proximal duodenum to the pancreas and participate to the pre absorptive phase of postprandial insulin secretion. EP neurons may therefore play a critical role in the postprandial inhibition of hepatic gluconeogenesis mandatory for an adequate postprandial glucose tolerance and a good overall insulin sensitivity. To test this hypothesis, modified oral glucose tolerance tests (mOGTT) were performed every 2 months for 6 months in intact (n = 3) and EP denervated minipigs (n = 4). An euglycemic hyperinsulinemic clamp procedure (EHC) was performed at the end of the experiment to estimate insulin sensitivity. EP denervation was achieved by sectioning the connective tissue between the pancreas and the proximal duodenum. The mOGGT consisted in the standard daily ration plus 1.5 g of glucose per kg of body weight. Postprandial glycemia and insulinemia were not affected by the EP denervation (P = 0.86 and P = 0.46 for glycemia and insulinemia respectively). The insulinogenic index (ISI = AUCinsulin/AUCglucose) was not significantly different in IEP and XEP animals either (P = 0.13). The final EHC highlighted a tendency for XEP to be less insulin sensitive than IEP (P = 0.09). We concluded that EP neurons were not mandatory for an adequate postprandial glucose tolerance but might contribute to the overall insulin sensitivity in pigs.