Bile enhances release of insulin: An incretin-mediated effect

Ingestion of food stimulates secretion of bile and release of gut hormones that enhance nutrient-stimulated release of insulin. The extent of physiologic participation of bile in the enteroinsular axis was examined in seven conscious dogs (weight: 20 ± 2 kg) that were prepared for study with chronic cannulas placed in the duodenum opposite the ampulla of Vater. On separate days, a meal consisting of 10 gm (MG-10), 25 gm (MG-25), or 62 gm (MG-62) of glucose (dextrose) was given orally in the presence of normal bile flow or during bile diversion. Bile diversion was achieved by catheterization of the common bile duct via the duodenal cannula. The insulin responses (given as ng [0-120]min/ml) to the different glucose meals, with bile present (BP) or absent (BA) in the lumen, were as follows: MG-10, 81 ± 8 BP and 72 ± 11 BA; MG-25, 172 ± 25 BP and 100 ± 6 BA (p < 0.05); and MG-62, 390 ± 79 BP and 153 ± 32 BA (p < 0.05). Only MG-25 and MG-62 produced a significant elevation of plasma glucose concentrations. Release of gastrin was not affected by either the presence of bile or the glucose content of the meal. We conclude that (1) endogenous bile enhances nutrient-stimulated release of insulin, (2) this effect is glucose-dependent with a threshold of approximately 1 gm/kg of glucose, and (3) bile may facilitate the release of insulinotropic hormones other than gastrin.