Hepatic production

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Estrogen may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance, thus increasing serum total thyroxine (tT4) and, to a lesser extent, total triiodothyronine (tT3). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as... 

Hyperglycemia Hyperglycemia is caused by increased hepatic production of glucose, combined with diminished peripheral use. Ketosis is usually minimal or absent in type 2 patients because the presence of insulin—even in the presence of insulin resistance—diminishes hepatic ketogenesis. 

Acute steatosis of the liver may have explained this presentation. In insulin overdose, the combination of greatly increased hepatic production of triglycerides from glucose and reduced production of apolipoprotein B 100 results in an insufficient increase in the transport of triglycerides in VLDL particles from liver to muscle and adipose tissue and contributes to the steatosis. 

A decreased triglyceride secretion with exercise has also been reported by Dall Agllo and associates (70) however, the magnitude of the decrease could not be accounted for by a decrease just in hepatic production. The results of this study indicate that both extrahepatlc and hepatic mechanisms are Involved in the exercise-induced reduction of plasma triglycerides. 

Qureshi (168) first isolated tocotrienols from barley and proved that they could suppress the hepatic production of cholesterol through their ability to suppress the activity of the enzyme HMG-CoA reductase, which regulates cholesterol synthesis in the liver. 

Anticoagulation Poor hepatic production of coagulation factors Poor dietary intake Anticoagulants Thrombolytics... 

Both direct inhibition of the hepatic production of vitamin K-dependent clotting factors and alterations in the intestinal flora, with subsequent reduction of microbial supply of vitamin K, have been imphcated (92,93). The relative role of either mechanism is difficult to assess, but experimental support for the flora theory is weak (94,95). 

Nonsulfonylureas Nonsulfonylureas decrease hepatic production of glucose from stored glycogen, resulting in reduced increase in serum glucose after a meal and limits the degree of postprandial (after a meal) hyperglycemia. 

The increased fat mass in obese individuals, associated with enhanced lipolysis in insulin-resistant NIDDM, leads to elevated plasma FFA and stimulates lipid oxidation by peripheral tissues. In non-insulin-dependent diabetics, ketone formation, however, is not increased because sufficient insulin is available to restrain hepatic production and stimulate peripheral utilization. 

AMG is also believed to modulate immunological and inflammatory reactions. Complexing of cytokines to protease-reacted AMG reduces cytokine-mediated hepatic production of APR. It, along with AAT, inhibits H2O2 release by polymorphonuclear leukocytes at the same time, it enhances phagocytosis of streptococci and perhaps other organisms. 

The elevated estrogen concentration stimulates increased hepatic production of CBG. The hepatic clearance of cortisol decreases. Thus, the absolute plasma concentrations of both total and free cortisol are several times higher during pregnancy. The diurnal rhythm of cortisol, higher in the morning and lower in the evening, is maintained. Increased plasma aldosterone and deoxycorticosterone concentrations are also observed. 

Other dietary interventions or diet supplements may be useful in certain patients with lipid disorders. Increased intake of soluble fiber in the form of oat bran, pectins, certain gums, and psyllium products can result in useful adj unctive reductions in total and LDL cholesterol, but these dietary alterations or supplements should not be substimted for more active forms of treatment. Total daily fiber intake should be about 20 to 30 g/day, with about 25%, or 6 g/day, being soluble fiber. Studies with psyllium seed in doses of 10 to 15 g/day show reductions in total and LDL cholesterol ranging from about 5% to 20% They have little or no effect on HDL cholesterol or triglyceride concentrations. These products also may be useful in managing constipation associated with the bile acid sequestrants. Psyllium binds cholesterol in the gut but also reduces hepatic production and clearance. Fish... 

A wide variety of data firom many laboratories indicates that the liver is a major source of somatomedin peptides. This has been demonstrated directly in studies of isolated perfused livers (F3, K13, MIO, P9, S9, S2I, W6), fetal (D14, R5) and adult (B25, S13) liver in organ culture, rat liver cell lines (M5, M26, S27), and primary hepatocyte cultures (K14, S22, S28). Tliese studies are supported by the observations that partial hepatectomy (U3) or liver disease (S14, T5) results in low circulating somatomedin activity. It has not always been clear, however, which members of the somatomedin family were being assayed in some of these studies, due to the broad specificity of the assays used (see Section 5). For example, whereas it has been well established that the BRL (buffalo rat liver) cell line, and fetal rat liver in organ culture (R5), produce peptides of the MSA or IGF-II family (M5, M26), it is not known whether normal adult liver produces IGF-II. Indeed, production of SM-G/IGF-I by adult liver has been demonstrated specifically in only two studies. In these, Schwander et al. (S21) found that a S-labeled product from perfused liver could be immunoprecipitated with an IGF-I antiserum, and Scott et al. (S22) used a specific SM-C/IGF-I RIA to demonstrate production of the peptide by adult hepatocytes in primary culture. In both studies, the measured hepatic production rate was calculated to be sufficient to account fully for circulating SM-C/IGF-I levels. 

It may be concluded from a number of the studies described above that the liver is the source of the majority of the SM-C/IGF-I in the circulation (the main source of circulating IGF-II in adults is entirely unknown). Since most other tissues appear to produce their own somatomedins, this raises the question of the function of the circulating peptide. It has been postulated that, particularly in the fetus, these growth factors exert their biological effects on the cells which produce them, or on nearby cells that is, that they act by autocrine or paracrine, rather than endocrine, mechanisms (DI4, DIG). If this is so in adult tissues, the reason for the high hepatic production rate is unexplained, since liver cell membranes contain very few SM-C/IGF-I receptors (see Section 4.2) and, with the exception of one study in which an incompletely characterized somatomedin preparation was used (B8), no ac-... 

Niacin Activates LPL reduces hepatic production of VLDL reduces catabolism of HDL f 22-25% f 10-25% t 15-35% f 20-50%... 

Insulin normally inhibits lipolysis by decreasing the lipolytic activity of HSL in the adipocyte. Individuals such as Di Abietes, who have a deficiency of insulin, have an increase in lipolysis and a subsequent increase in the concentration of free fatty acids in the blood. The liver, in turn, uses some of these fatty acids to synthesize triacylglycerols, which then are used in the hepatic production of VLDL. VLDL is not stored in the liver but is secreted into the blood, raising its serum concentration. Di also has low levels of LPL because of decreased insulin levels. Her hypertriglyceridemia is the result, therefore, of both overproduction of VLDL by the liver and decreased breakdown of VLDL triacylglycerol for storage in adipose cells. 

Folate deficiencies frequently occur in individuals with chronic alcoholism. A number of factors are involved inadequate dietary intake of folate direct damage to intestinal cells and brush border enzymes, which interferes with absorption of dietary folate a defect in the enterohepatic circulation, which reduces the absorption of folate liver damage causing decreased hepatic production of plasma proteins and interference with kidney resorption of folate. 

Most cells of the body have rtiRNA for IGF, but the liver has the greatest concentration of these messengers, followed by kidney and heart. The synthesis of IGF-I is regulated, for the most part, by GH, whereas hepatic production of IGF-II is independent of GH levels in the blood. 

With regard to triacylglycerol levels in patients with severe parenchymal liver disease, the hepatic production of the triacylglycerol-rich, very-low-density lipoprotein (VLDL) particle is impaired. Yet the total level of plasma triacylglycerols remains relatively normal because the LDL particle in such patients is triacylglyc-erol-rich, for reasons that have not been fully elucidated. 

Atorvastatin, rosuvastatin, and simvastatin appear to have some effects beyond those seen with the other HMGRIs. These compounds have been shown to decrease plasma LDL levels in patients with homozygous familial hypercholesterolemia, an effect that is proposed to result from their ability to produce a more significant decrease in the hepatic production of LDL cholesterol. Additionally, atorvastatin and rosuvastatin can produce a significant lowering in plasma triglycerides. In the case of atorvastatin, this effect has been attributed to its ability to produce an enhanced removal of triglyceride-rich VLDL (15,36,37). 

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