Insulin plays an important role in the regulation of lipid metabolism. The main sites of action of insulin on lipoprotein metabolism are shown in . Insulin has an antilipolytic effect by inhibiting hormone-sensitive lipase (HSL) in adipose tissue. As a consequence insulin reduces the secretion of free fatty acids (FFAs) from adipose tissue. Postprandially, the enterocytes produce large lipoproteins, the chylomicrons, whose main apolipoprotein is apoB48. In the circulation, lipoprotein lipase (LPL) hydrolyzes the triglycerides within the chylomicrons leading to the formation of smaller particles, the chylomicron remnants, that are taken up by the liver via the LDL receptor or the LDL receptor-related protein (LRP). Insulin significantly influences postprandial lipid metabolism by reducing chylomicron production through increasing LPL activity, which accelerates chylomicron catabolism by increasing the expression of the LDL receptor and LRP, leading to enhanced chylomicron-remnant catabolism . The liver produces the very low density lipoproteins (VLDLs) whose main apolipoprotein is the apoB100. In plasma, VLDLs are hydrolyzed by LPL, leading to the formation of intermediatedensity lipoproteins (IDLs), which are further hydrolyzed through additional lipolysis involvinghepatic lipase and are converted to low-density lipoproteins (LDLs). Insulin inhibits the hepatic production of VLDLs. The inhibition of VLDL production by insulin is due to both its antilipolytic effect – that reduces circulating FFAs which are substrates for VLDL – and to a direct inhibitory effect in hepatocytes via different mechanisms including inhibition of microsomal triglyceride transfer protein (MTP) . In addition, insulin, which is a potent activator of LPL, promotes VLDL catabolism . LDLs are taken up into cells via binding to the LDL receptor on the plasma membrane of hepatic or other tissues. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating LDL receptor activity by binding to the LDL receptor/LDL complex and directing the receptor away from recycling back to the surface, and redirecting it into the lysosomal catabolic pathway. Insulin increases LDL receptor expression and activity, and thus promotes LDL catabolism . HDLs are synthesized by both the liver and the intestine as nascent HDLs that contain only apolipoproteins (mainly apoA-I). Nascent HDLs acquire cholesterol from peripheral tissues, including macrophages within artery walls, through the membrane-associated ATP-binding cassette A1 (ABCA1) and G1 (ABCG1) transporters. Within the HDL particle, free cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT). HDLs exchange lipids with VLDLs in a process involving cholesteryl ester transfer protein (CETP), whereby cholesteryl esters are transferred from HDLs to VLDLs and, reciprocally, triglycerides are transferred from VLDLs to HDLs. During this process, HDLs become enriched in triglycerides which are catabolized by hepatic lipase, thus forming smaller HDL particles that can be cleared by the liver via the scavenger receptor B1 (SR-B1). Endothelial lipase is a phospholipase that modulates HDL catabolism. Several studieshave shown that its activity is mainly promoted by inflammatory cytokines. Insulin does not seem to exert any significant direct effects on LCAT, hepatic lipase, or CETP activity.

Regards,

Jessica

Managing editor

Pancreatic disorder and therapy.