Bolivian squirrel monkeys (Saimiri sciureus) have fasting unconjugated hyperbilirubinemia (males: 2.0 ± 0.14; females: 3.0 ± 0.26 mg per dl) which resembles that of humans with Gilbert's syndrome. Closely related Brazilian squirrel monkeys have fasting levels (males: 0.29 ± 0.045; females: 0.36 ± 0.073 mg per dl) similar to normal people. The purpose of this study was to identify the underlying mechanisms and the nutritional factors involved. Both Bolivian and Brazilian squirrel monkeys had higher plasma bilirubin concentrations after an 18 hr fast than 4 hr after feeding. The development of fasting hyperbilirubinemia was progressive for at least 24 hr. Both populations that received a semipurified diet containing 5% fat had lower fasting and postprandial plasma bilirubin concentrations than did animals receiving 0.3% fat but much lower than those receiving 20% fat. The emulsified complete meal, or glucose, sucrose, casein, or lactalbumin alone when given by intragastric tube lowered the plasma bilirubin levels of Bolivian monkeys to less than one‐half of fasting values within 1 to 4 hr. Water or butter did not have a significant effect. Glucose or fructose, when given intravenously, lowered the plasma bilirubin levels to less than half of fasting values; the fat emulsion, Intralipid, did not have a statistically significant effect. Subcutaneous epinephrine increased plasma glucose concentrations and reduced plasma bilirubin concentrations. When glucose or glucose plus butter were given by stomach tube to Bolivian squirrel monkeys for 48 hr, a very low plasma bilirubin concentration resulted whereas butter given alone resulted in high values. Fasting Bolivian squirrel monkeys had impaired plasma clearance of [3H]bilirubin; intravenous glucose normalized the pattern. Glucose administration markedly increased excretion of bilirubin into bile. Glucose or bilirubin given intravenously or sucrose administered by gastric tube lowered plasma bile acid concentrations. The complete ration or fat given alone by gastric tube raised plasma bile acid concentrations. Thus carbohydrate, but not fat, lowered fasting hyperbilirubinemia and increased bilirubin excretion in Bolivian squirrel monkeys. Exogenous glucose may increase the availability of UDP‐glucuronate for hepatic conjugation of bilirubin in the fasting subject.
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