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Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia.

Authors: Caron, S  Verrijken, A  Mertens, I  Samanez, CH  Mautino, G  Haas, JT  Duran-Sandoval, D  Prawitt, J  Francque, S  Vallez, E  Muhr-Tailleux, A  Berard, I  Kuipers, F  Kuivenhoven, JA  Biddinger, SB  Taskinen, MR  Van Gaal, L  Staels, B 
Citation: Caron S, etal., Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):513-9. doi: 10.1161/ATVBAHA.110.220723. Epub 2010 Dec 23.
Pubmed: (View Article at PubMed) PMID:21183731
DOI: Full-text: DOI:10.1161/ATVBAHA.110.220723

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-4alpha. ApoCIII induction by glucose is blunted by treatment with agonists of farnesoid X receptor and peroxisome proliferator-activated receptor-alpha 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. CONCLUSIONS: Glucose induces apoCIII transcription, which may represent a mechanism linking hyperglycemia, hypertriglyceridemia, and cardiovascular disease in type 2 diabetes.

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CRRD Object Information
CRRD ID: 7207206
Created: 2013-01-23
Species: All species
Last Modified: 2013-01-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.