title: Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis.
abstract: Cholestasis is associated with systemic accumulation of bile salts and with deficiency of bile in the intestinal lumen. During the past years bile salts have been identified as signaling molecules that regulate lipid, glucose, and energy metabolism. Bile salts have also been shown to activate signaling routes leading to proliferation, apoptosis, or differentiation. It is unclear, however, whether cholestasis affects the constitution and absorptive capacity of the intestinal epithelium in vivo. We studied small intestinal morphology, proliferation, apoptosis, expression of intestine-specific genes, and carbohydrate absorption in cholestatic (1 wk bile duct ligation), bile-deficient (1 wk bile diversion), and control (sham) rats. Absorptive capacity was assessed by determination of plasma [(2)H]- and [(13)C]glucose concentrations after intraduodenal administration of [(2)H]glucose and naturally enriched [(13)C]sucrose, respectively. Small intestinal morphology, proliferation, apoptosis, and gene expression of intestinal transcription factors (mRNA levels of Cdx-2, Gata-4, and Hnf-1alpha, and Cdx-2 protein levels) were similar in cholestatic, bile-deficient, and control rats. The (unlabeled) blood glucose response after intraduodenal administration was delayed in cholestatic animals, but the absorption over 180 min was quantitatively similar between the groups. Plasma concentrations of [(2)H]glucose and [(13)C]glucose peaked to similar extents in all groups within 7.5 and 30 min, respectively. Absorption of [(2)H]glucose and [(13)C]glucose in plasma was similar in all groups. The present data indicate that neither accumulation of bile salts in the body, nor their intestinal deficiency, two characteristic features of cholestasis, affect rat small intestinal proliferation, differentiation, apoptosis, or its capacity to digest and absorb carbohydrates.
authors.affiliation: Pediatric Gastroenterology/Research Laboratory of Pediatrics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: E Leonie
authors.initials: EL
authors.lastname: Los
authors.forename: Henk
authors.initials: H
authors.lastname: Wolters
authors.forename: Frans
authors.initials: F
authors.lastname: Stellaard
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.forename: Edmond H H M
authors.initials: EH
authors.lastname: Rings
mesh_terms: D000818:Animals; D017209:Apoptosis; D001647:Bile Acids and Salts / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D001652:Bile Ducts / Q000601:surgery; D001786:Blood Glucose / Q000378:metabolism; D000071616:CDX2 Transcription Factor; D002247:Carbon Isotopes; D002454:Cell Differentiation; D049109:Cell Proliferation; D001651:Cholestasis, Extrahepatic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000378:metabolism*; D019422:Dietary Sucrose / Q000378:metabolism; D004063:Digestion; D004195:Disease Models, Animal; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D050356:Lipid Metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D000071616:CDX2 Transcription Factor; D002247:Carbon Isotopes; D004040:Dietary Carbohydrates; D019422:Dietary Sucrose; D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D005947:Glucose