How Lipoproteins Affect Metabolism in Diabetes

in diabetes there is abnormal lipoprotein metabolism very low-density lipoproteins VLDL are secreted from the liver into the blood circulation these VLDL molecules are then transported to the capillaries of peripheral tissues where they are exposed to an enzyme called lipoprotein lipase this enzyme functions to break down the v LDL particles thereby converting them to intermediate density lipoproteins this conversion also creates free fatty acids which get released into body tissues concurrently the LDL remnants or intermediate density lipoprotein IDL particles circulate back to the liver from the peripheral tissues once at the liver the particles are acted upon by the enzyme hepatic lipase an enzyme that specifically breaks down intermediate density lipoproteins this results in the production of fatty acids and low-density lipoproteins triglyceride rich lipoprotein particles are able to enter liver hepatocytes because of the large open pores or finestra the low-density lipoproteins retain aple B protein and return to the circulation some of the LDL particles that are products of intermediate density lipoprotein metabolism return to the general circulation other LDL particles bind to specific LDL receptors found on the surface of the hepatocytes and thereby get cleared from the circulation increased glycation and oxidation of LDLs and diabetes in the diabetic environment low-density lipoproteins are typically exposed to high levels of circulating glucose from this exposure these low-density lipoproteins become glycated that is a molecule of glucose becomes attached to them this animation shows glucose attaching to an LDL thus forming a glycated LDL similarly some LDL particles are modified instead by reactive oxygen species and become oxidized LDL particles increase formation of small dense LDLs in diabetes this animation shows the formation of triglyceride rich LDL particles here LDL exchanges cholesterol esters for triglycerides with a V LDL particle this exchange is facilitated by the cholesterol ester transfer protein shown in green cholesterol ester transfer protein therefore helps to convert very low-density lipoproteins into very low-density lipoprotein remnants or intermediate density lipoproteins triglyceride enriched low-density lipoprotein particles are transported by the blood to the liver when these triglyceride rich LDL particles arrive at the liver they are further modified through the action of hepatic lipase this enzyme removes the triglycerides causing the particles to break apart into three components free fatty acids monoglycerides and the now small dense low-density lipoproteins there are several key roles that small dense LDL molecules play in the progression of cardiovascular disease the first feature is that these modified particles have a lower affinity for normal clearance by LDL receptor sites on the surface of hepatocytes as a result normal binding does not occur and instead the small dense LDL particles bind poorly to the LDL receptor from the liver these small dense LDL particles enter the circulation and travel to the coronary artery here the small dense LDL particle travels in the circulation to the coronary artery once the small dense LDL particles reach the endothelial wall of the coronary artery they gain access through this barrier and penetrate into the sub endothelial cell DL particles have a higher permeability through the endothelial wall once in the sub endothelial matrix another key feature of cardiovascular disease progression occurs that is the increased retention of small dense LDL particles these retained particles remain in the sub endothelial matrix for a sufficient amount of time to undergo further modification specifically these retained small dense LDL particles are susceptible to oxidation and become oxidized small dense LDL particles reduction of HDLs in diabetes in diabetes high density lipoprotein HDL levels are also reduced HDL particles exchange cholesterol esters for triglycerides of april-b containing lipoproteins through the action of a cholesterol ester transfer protein this results in the formation of triglyceride enriched HDL particles this is similar to what we saw happen earlier to the LDL particles triglyceride enriched HDL particles once circulated to the liver are more likely to enter hepatocyte become acted upon by hepatic lipase and thus removed from general circulation this increased clearance leads to reduced levels of circulating HDL cholesterol in summary there are multiple lipid abnormalities that can be found in diabetes these include an increased level of glycated oxidized and small dense LDL particles along with a reduced level of HDL cholesterol these abnormalities interplay to contribute to the development of the accelerated atherosclerosis of diabetes

Channel: Mechanisms in Medicine

Views: 68,307

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Keywords: lipids, lipoprotein, VLDL, LDL, HDL, diabetes

Id: 9zb0Oo0ryEI

Length: 6min 38sec (398 seconds)

Published: Tue Jul 16 2013