The gastrointestinal tract is known to generate hormonal and neural signals that can affect the endocrine function of the pancreas ("enteroinsular axis"). The physiological circumstances under which this connection is operative are still a matter of debate. We investigated the influence of bile flow on glucose homeostasis in an experimental model of internal biliary diversion. After laparotomy in 2-mo-old rats, bile flow was diverted from the duodenum into the second jejunal loop with the use of a plastic minicannula. Rats in which the cannula was implanted but not connected with the common bile duct (sham operation) and rats receiving no treatment were used as control groups. After surgery, the rats with the biliary bypass weighed 10% less than the controls for 3 wk; afterwards and until 9 mo later, operated and nonoperated animals had similar growth curves. After the operation, fasting plasma glucose concentrations fell significantly in the treated rats compared with both sham-operated and control rats; likewise, the glycemic response to orally administered glucose was lower in the treated group 1 wk after surgery. In contrast, no significant difference was found in either the fasting or the glucose-induced plasma insulin levels. Nine months after surgery, the same three groups of animals received an oral glucose tolerance test, an intravenous glucose tolerance test, and a fasting-refeeding test (24 h of fast followed by standard, mixed feeding for another 24 h). On all three tests, bile-diverted rats showed lower plasma glucose responses than either sham-operated or control rats in the face of essentially similar plasma insulin responses.(ABSTRACT TRUNCATED AT 250 WORDS)