Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia
| Autor: | Emmanuelle Vallez, Luc Van Gaal, Ilse Mertens, Bart Staels, Sven Francque, An Verrijken, Daniel Duran-Sandoval, Jan Albert Kuivenhoven, Isabelle Berard, Janne Prawitt, Folkert Kuipers, Carolina Huaman Samanez, Sudha B. Biddinger, Anne Muhr-Tailleux, Joel T. Haas, Sandrine Caron, Gisèle Mautino, Marja-Riitta Taskinen |
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| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), ACS - Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Blood Glucose
Male Time Factors medicine.medical_treatment nuclear receptors Receptors Cytoplasmic and Nuclear Type 2 diabetes 030204 cardiovascular system & hematology APOC-III Mice 0302 clinical medicine Insulin Promoter Regions Genetic Cells Cultured Heat-Shock Proteins Liver X Receptors Mice Knockout 0303 health sciences type II diabetes INSULIN-RESISTANCE PLASMA Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Fatty liver RNA-Binding Proteins Middle Aged Orphan Nuclear Receptors Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 3. Good health Up-Regulation A-I Hepatocyte Nuclear Factor 4 RECEPTOR LXR RNA Interference Cardiology and Cardiovascular Medicine Adult Transcriptional Activation medicine.medical_specialty C-III LEVELS LOW-DENSITY-LIPOPROTEIN Carbohydrate metabolism Biology Transfection lipids Diabetes Complications 03 medical and health sciences Insulin resistance Internal medicine medicine Animals Humans Obesity RNA Messenger Liver X receptor 030304 developmental biology Dyslipidemias Apolipoprotein C-III GENE-TRANSCRIPTION medicine.disease ELEMENT-BINDING PROTEIN Receptor Insulin Rats Endocrinology Glucose Hepatocyte nuclear factor 4 Diabetes Mellitus Type 2 Hepatocytes Farnesoid X receptor Human medicine apolipoproteins metabolism TRIGLYCERIDE-RICH LIPOPROTEINS Transcription Factors |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology Arteriosclerosis thrombosis and vascular biology, 31(3), 513-U72. LIPPINCOTT WILLIAMS & WILKINS Arteriosclerosis, thrombosis, and vascular biology, 31(3), 513-U72. Lippincott Williams and Wilkins University of Helsinki |
| ISSN: | 1079-5642 |
| Popis: | Objective— Hypertriglyceridemia and fatty liver are common in patients with type 2 diabetes, but the factors connecting alterations in glucose metabolism with plasma and liver lipid metabolism remain unclear. Apolipoprotein CIII (apoCIII), a regulator of hepatic and plasma triglyceride metabolism, is elevated in type 2 diabetes. In this study, we analyzed whether apoCIII is affected by altered glucose metabolism. Methods and Results— Liver-specific insulin receptor–deficient mice display lower hepatic apoCIII mRNA levels than controls, suggesting that factors other than insulin regulate apoCIII in vivo. Glucose induces apoCIII transcription in primary rat hepatocytes and immortalized human hepatocytes via a mechanism involving the transcription factors carbohydrate response element–binding protein and hepatocyte nuclear factor-4α. ApoCIII induction by glucose is blunted by treatment with agonists of farnesoid X receptor and peroxisome proliferator-activated receptor-α but not liver X receptor, ie, nuclear receptors controlling triglyceride metabolism. Moreover, in obese humans, plasma apoCIII protein correlates more closely with plasma fasting glucose and glucose excursion after oral glucose load than with insulin. Conclusion— Glucose induces apoCIII transcription, which may represent a mechanism linking hyperglycemia, hypertriglyceridemia, and cardiovascular disease in type 2 diabetes. |
| Databáze: | OpenAIRE |
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