title: Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters.
abstract: Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17β-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17β-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas; College of Korean Medicine, Gachon University, Seongnam, Korea;
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamabe
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas; College of Korean Medicine, Gachon University, Seongnam, Korea; Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do, Korea; and.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Kang
authors.affiliation: Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do, Korea; and.
authors.forename: Woojung
authors.initials: W
authors.lastname: Lee
authors.affiliation: Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do, Korea; and.
authors.forename: Su-Nam
authors.initials: SN
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas; Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, China BTZhu@SUSTC.edu.cn.
authors.forename: Bao Ting
authors.initials: BT
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D018938:Caco-2 Cells; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051273:Glucose Transporter Type 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D019518:Postprandial Period / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; C495683:Slc2a2 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D004958:Estradiol; D004964:Estriol
keywords: 17β-estradiol; GLUT2; SGLT1; estriol; postprandial blood glucose level