Secretion of an insulinotropic factor from isolated, perfused rat intestine.

To examine gut-islet interrelationships, we entirely separated the gastrointestinal tract from the rat. When we arterially perfused this preparation with an erythrocyte-free solution for 1 h, it remained histologically intact and took up oxygen and glucose. Feedings were given via a duodenal tube. The gut absorbed glucose when glucose in the feeding was high (9.2 g/dl), but not when glucose in the feeding was low (58 mg/dl). With feeding, the portal venous effluent (PVE) from this preparation (stomach to ileum) enhanced late-phase, glucose-induced insulin secretion from pancreas of another rat. This enhancement occurred when the gut was fed either glucose (9.2 g/dl) in electrolyte solution or electrolyte solution alone. PVE from glucose-fed upper gut (stomach, duodenum) was similarly insulinotropic. In contrast, PVE from unfed gut or from glucose-fed gut of old rats was not insulinotropic. PVE from all gut preparations except upper gut produced a glucagon "spike" during basal pancreatic perfusion. Effects of gastrointestinal peptides (gastric inhibitory polypeptide, cholecystokinin octapeptide, secretin, gastrin) and immunoassays of PVE suggested that the insulinotropic substance is not one of these peptides. Thus, an insulinotropic substance that is not dependent on feeding nutrient material is secreted from the intestine.