In Vitro Transcriptional Induction of the Human Apolipoprotein A-II Gene by Glucose

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 3; pp. 672 - 678
• Main Authors: SAUVAGET, Dominique, CHAUFFETON, Valérie, DUGUE-PUJOL, Sonia, KALOPISSIS, Athina-Despina, GUILLET-DENIAU, Isabelle, FOUFELLE, Fabienne, CHAMBAZ, Jean, LETURQUE, Armelle, CARDOT, Philippe, RIBEIRO, Agnès
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2004
• Subjects: Animals; Apolipoprotein A-II - genetics; Apolipoproteins; Atherosclerosis; Base Sequence; Biological and medical sciences; Blood Glucose - metabolism; Carbohydrates; Cardiovascular disease; Case studies; Coronary heart disease; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Diabetics; DNA Primers; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Gene expression; Gene Expression Regulation - drug effects; General and cellular metabolism. Vitamins; Genetic aspects; Genetic transcription; Glucose; Glucose - pharmacology; Health aspects; High density lipoprotein; Humans; Hyperglycemia; Liver - physiology; Medical sciences; Metabolism; Mice; Mice, Transgenic; Pharmacology. Drug treatments; Physiology; Plasma; Polymerase Chain Reaction - methods; Risk factors; RNA, Messenger - genetics; Transcription (Genetics); Transcription, Genetic - drug effects; Transgenic animals; France; Endocrinopathy; Human; Apolipoprotein A; Gene; Diabetes mellitus; Glucose; In vitro
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.3.672

In Vitro Transcriptional Induction of the Human Apolipoprotein A-II Gene by Glucose Dominique Sauvaget 1 2 , Valérie Chauffeton 2 , Sonia Dugué-Pujol 1 2 , Athina-Despina Kalopissis 1 2 , Isabelle Guillet-Deniau 3 , Fabienne Foufelle 2 4 , Jean Chambaz 1 2 , Armelle Leturque 1 2 , Philippe Cardot 1 2 and Agnès Ribeiro 1 2 1 Institut National de la Santé et de la Recherche Médicale (INSERM) U505, Institut Biomédical des Cordeliers, Paris, France 2 Institut Fédératif de Recherche 58, Institut Biomédical des Cordeliers, Paris, France 3 INSERM U567, Unité Mixte de Recherche 8104 Centre National de la Recherche Scientifique, Institut Cochin, Paris, France 4 INSERM U465, Institut Biomédical des Cordeliers, Paris, France Address correspondence and reprint requests to Agnès Ribeiro, INSERM U505, 15 rue de l’Ecole de Médecine, 75006 Paris, France. E-mail: agnes.ribeiro-pillet-u505{at}bhdc.jussieu.fr Abstract Type 2 diabetic patients present high triglyceride and low HDL levels, significant determinants for the risk of atherosclerosis. Transgenic mice overproducing human apolipoprotein (apo)A-II, one of the two major apos of HDLs, display the same lipid disorders. Here, we investigated the possible regulation of apoA-II gene expression by glucose. In primary rat hepatocytes and in HepG2 cells, the transcription of the human apoA-II gene was upregulated by glucose. This response was mediated by a hormone-responsive element within the enhancer of the apoA-II promoter and was dependent on hepatocyte nuclear factor-4α. Accordingly, in transgenic mice, the human apoA-II gene is stimulated by a high-carbohydrate diet after fasting and at weaning. By contrast, the apoA-II mRNA level is not modified in streptozotocin-induced diabetic rats. In transgenic mice overexpressing the human apoA-II gene, plasma human apoA-II concentration was positively correlated with blood glucose levels. These mice displayed a marked delay in plasma glucose tolerance as compared with control mice. We hypothesize that the following pathogenic pathway might occur in the course of type 2 diabetes: increased apoA-II level causes a rise in plasma triglyceride level and glucose intolerance, resulting in hyperglycemia, which in turn might further increase apoA-II gene transcription. apo, apolipoprotein CAD, coronary artery disease CAT, chloramphenicol acetyl transferase ChoRE, carbohydrate response element DMEM, Dulbecco’s modified Eagle’s medium HNF, hepatocyte nuclear factor HRE, hormone responsive element INSERM, Institut National de la Santé et de la Recherche Médicale MODY1, type 1 maturity-onset diabetes of the young PSK, pBluescript SK RCT, reverse cholesterol transport Footnotes Accepted December 1, 2003. Received June 25, 2003. DIABETES