title: Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.
abstract: Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme--UDP-glucuronosyltransferase (UGT) 1A1--to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined in the liver and small intestine of neonatal hUGT1 mice that were orally treated with glucose. In the hUGT1 mice, glucose induced UGT1A1 in the small intestine, while it did not affect the expression of UGT1A1 in the liver. UGT1A1 was also induced in the human intestinal Caco-2 cells when the cells were cultured in the presence of glucose. Luciferase assays demonstrated that not only the proximal region (-1300/-7) of the UGT1A1 promoter, but also distal region (-6500/-4050) were responsible for the induction of UGT1A1 in the intestinal cells. Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, JAPAN.
authors.forename: Naoya
authors.initials: N
authors.lastname: Aoshima
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, JAPAN.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fujie
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, JAPAN.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Tukey
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, JAPAN.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Fujiwara
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000097:blood*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D005947:Glucose / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000517:prevention & control*; D007231:Infant, Newborn; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D005947:Glucose; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme