To determine whether the appearance of nutrients into the gastric lumen per se provokes insulin secretion, glucose solution was instilled into the pylorus-cannulated stomach via an orogastric tube in anesthetized dogs. When 200 ml of 0, 5, 10, and 20% glucose solution were sequentially instilled, transgastric gradients (TGG) of plasma glucose concentration across the fundus [short gastric vein (SGV)  femoral artery, TGG(SGV)] and insulin levels in the superior pancreaticoduodenal vein (SPDV) increased stepwise. Upon instillation of 300 ml of 10% glucose, but not 1.8% saline, for 12 min followed by 48-min spontaneous drainage via the cannula (n = 5 each), TGG(SGV) and insulin levels in the SPDV increased concomitantly and significantly by 0.95 mM and 1,334 pM (mean), respectively, regardless of unaltered arterial glucose levels. The amount of secreted insulin (area under the curve) significantly correlated with the maximum TGG(SGV) (r = 0.693). In selectively gastric-vagotomized dogs (n = 5), insulin levels in the SPDV did not increase upon instillation despite a TGG(SGV) rise comparable to that in normal dogs. These results indicate that intragastric glucose appearance provokes vagus-mediated insulin secretion probably related to the transfundic glucose flux, suggesting the presence of a novel neurogenic gastroinsular axis.