NDLI: Modulation of intestinal cholesterol absorption by high glucose levels: impact on cholesterol transporters, regulatory enzymes, and transcription factors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ravid, Z. Bendayan, M. Delvin, E. Sane, A. T. Elchebly, M. Lafond, J. Lambert, M. Mailhot, G. Levy, E.
Description	Author Affiliation: Ravid Z ( Research Centre, CHU-Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5.)
Abstract	Growing evidence suggests that the small intestine may contribute to excessive postprandial lipemia, which is highly prevalent in insulin-resistant/Type 2 diabetic individuals and substantially increases the risk of cardiovascular disease. The aim of the present study was to determine the role of high glucose levels on intestinal cholesterol absorption, cholesterol transporter expression, enzymes controlling cholesterol homeostasis, and the status of transcription factors. To this end, we employed highly differentiated and polarized cells (20 days of culture), plated on permeable polycarbonate filters. In the presence of [(14)C]cholesterol, glucose at 25 mM stimulated cholesterol uptake compared with Caco-2/15 cells supplemented with 5 mM glucose (P < 0.04). Because combination of 5 mM glucose with 20 mM of the structurally related mannitol or sorbitol did not change cholesterol uptake, we conclude that extracellular glucose concentration is uniquely involved in the regulation of intestinal cholesterol transport. The high concentration of glucose enhanced the protein expression of the critical cholesterol transporter NPC1L1 and that of CD36 (P < 0.02) and concomitantly decreased SR-BI protein mass (P < 0.02). No significant changes were observed in the protein expression of ABCA1 and ABCG8, which act as efflux pumps favoring cholesterol export out of absorptive cells. At the same time, 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was decreased (P < 0.007), whereas ACAT activity remained unchanged. Finally, increases were noted in the transcription factors LXR-alpha, LXR-beta, PPAR-beta, and PPAR-gamma along with a drop in the protein expression of SREBP-2. Collectively, our data indicate that glucose at high concentrations may regulate intestinal cholesterol transport and metabolism in Caco-2/15 cells, thus suggesting a potential influence on the cholesterol absorption process in Type 2 diabetes.
File Format	HTM / HTML
ISSN	01931857
Issue Number	5
Volume Number	295
e-ISSN	15221547
Journal	AJP: Gastrointestinal and Liver Physiology
Language	English
Publisher	American Physiological Society
Publisher Date	2008-11-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Physiology Discipline Gastroenterology Carrier Proteins Metabolism Cholesterol Glucose Pharmacology Intestines Membrane Proteins Transcription Factors Blotting, Western Caco-2 Cells Chemistry Dose-response Relationship, Drug Gene Expression Regulation Drug Effects Physiology Humans Immunohistochemistry Cytology Genetics Protein Isoforms Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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