Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c

TL;DR: This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care outside of the acute care setting.

TL;DR: Individuals with loss-of-function mutations in PCSK9 have reduced plasma levels of LDL cholesterol and are protected from CHD; these observations have validatedPCSK9 as a therapeutic target and suggested new approaches for the treatment and prevention of CHD.

TL;DR: This review will address the biochemical, genetic, and clinical aspects associated with PCSK9’s biology and pathophysiology in cells, rodent and human, with emphasis on the clinical benefits of silencing the expression/activity ofPCSK9 as a new modality in the treatment of hypercholesterolemia and associated pathologies.

TL;DR: Although levels of PCSK9 correlate with plasma levels of LDL-C, they account for only a small proportion of the variation in the levels of this lipoprotein.

TL;DR: It is reported that full induction of the mature and transcriptionally active form of SREBP-1c protein requires insulin and it is shown through experiments in suckling mice that this acute action of insulin to stimulate the proteolytic processing of S REBP- 1c is functional in vivo.

TL;DR: It is concluded that SREBPs are regulated by food consumption in the mouse liver and that the decline in nuclear SREBP-1c upon fasting may explain in part the decrease in mRNAs encoding enzymes of the fatty acid biosynthetic pathway.

TL;DR: It is concluded that insulin activates the SREBP-1c promoter primarily by increasing the activity of LXRs, possibly through production of a ligand that activates LXRs or their heterodimerizing partner, the retinoid X receptor.

TL;DR: It is concluded that SREBP-2 is a relatively selective activator of cholesterol synthesis, as opposed to fatty acid synthesis, in liver and adipose tissue of mice.