Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice

• Published in: The Journal of clinical investigation Vol. 122; no. 4; pp. 1262 - 1270
• Main Authors: Ai, Ding, Chen, Chiyuan, Han, Seongah, Ganda, Anjali, Murphy, Andrew J., Haeusler, Rebecca, Thorp, Edward, Accili, Domenico, Horton, Jay D., Tall, Alan R.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2012
• Subjects: Adenoviruses; Animals; Atherosclerosis; Biomedical research; Cellular signal transduction; Cholesterol; Diabetes; Gene expression; Gene Expression Regulation - drug effects; Health aspects; Hepatocyte Nuclear Factor 1-alpha - physiology; Hepatocyte Nuclear Factor 4 - physiology; Hyperinsulinism - genetics; Hyperinsulinism - metabolism; Insulin; Insulin - physiology; Insulin Resistance - physiology; Kinases; Liver; Liver - metabolism; Liver Transplantation; Low density lipoprotein; Low density lipoprotein receptors; Measurement; Mechanistic Target of Rapamycin Complex 1; Metabolic disorders; Metabolic syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Multiprotein Complexes; Phosphorylation; Physiological aspects; Postoperative Complications; Properties; Proprotein Convertase 9; Proprotein Convertases; Proteins; Proteins - antagonists & inhibitors; Proteins - physiology; Proto-Oncogene Proteins c-akt - physiology; Receptor, Insulin - antagonists & inhibitors; Receptor, Insulin - genetics; Receptor, Insulin - physiology; Receptors, LDL - biosynthesis; Receptors, LDL - genetics; RNA Interference; RNA, Small Interfering - pharmacology; Serine Endopeptidases - deficiency; Serine Endopeptidases - genetics; Serine Endopeptidases - physiology; Signal Transduction; Sirolimus - pharmacology; TOR Serine-Threonine Kinases; United States
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI61919

Individuals with type 2 diabetes have an increased risk of atherosclerosis. One factor underlying this is dyslipidemia, which in hyperinsulinemic subjects with early type 2 diabetes is typically characterized by increased VLDL secretion but normal LDL cholesterol levels, possibly reflecting enhanced...