Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons.
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PMID:Apoprotein composition of very low density lipoproteins of human serum. 17 34

The effect of the thymus polypeptide factor-thymidin on the lipid spectrum of the blood, thymic factor content in the blood and clinical course of the disease were studied in 156 patients with exertion stenocardia (II-IV functional class). Results indicate that patients with exertion stenocardia show with advance of the disease a reduction of the blood thymic factor and 85.6% develop hyperlipidemia. Complex treatment with inclusion of thymalin resulted in an increase of the thymic factor, normalization of the lipid metabolism increase of the contractile function of the myocardium and, thus, increases the treatment efficacy.
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PMID:[The effect of thymalin on lipid metabolism and the clinical course of ischemic heart disease]. 148 12

It was found that polyarginine (Mr 40 000-60 000) is a strong inhibitor of the lipoprotein lipase activity in vivo and in vitro. The inhibitory effect in vivo was observed after a single intravenous injection of 0.85-3.5 mg/kg to rabbits, that in vitro at the polypeptide concentration of greater than or equal to 2.5 micrograms/ml. Within the first few hours after intravenous injection of polyarginine hyperlipidemia occurred with an obvious increase in the plasma triglyceride and VLDL fractions and a slight decrease of the LDL and HDL fractions. These changes typical for reduced lipoprotein lipolysis were due to the formation of a polyarginine-heparin complex, on the one hand, and to the formation of a polyarginine-enzyme complex devoid of the lipolytic properties, on the other. The inhibitory effect of polyarginine on lipoprotein lipase is related to the whole polypeptide molecule or its large fragment, since arginine and metformine (bi-guanidine compound) have no effect on the enzyme activity.
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PMID:[Inhibition of lipoprotein lipolysis by polyarginine and evaluation of the mechanism of its interaction with lipoprotein lipase]. 400 23

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a "uremic toxin" responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant "uremic toxin."
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PMID:Parathyroid hormone metabolism and its potential as a uremic toxin. 699 9

Apolipoprotein E (apo E) plays a role in the regulation of the lipid metabolism of humans. Apo E, 229 amino acid polypeptide, is classified into three major isoform (E2, E3, E4) according to the differences of amino acid in position 112 and 158. In the normal population apo E3 isoform is most prevalent and apo E2 or E4 is frequently associated with hyperlipoproteinemia. To find out the frequency of apo E isoform distribution in the Korean population, apo E genotyping was performed. After amplification of apoE gene by polymerase chain reaction (PCR), restriction isotyping was done by cleavage with restriction enzyme Hha I and polyacrylamide gel electrophoresis. The apo E allele frequency in 73 normal subjects was 4.8% for E2, 84.9% for E3 and 10.3% for E4. In diabetic patient with hyperlipoproteinemia, the frequency of apo E allele was 6.3% for E2, 81.0% for E3 and 12.7% for E4. There was no significant difference in apo E isoform distribution between diabetics and normal populations. But in patients with cardiovascular disease with hyperlipidemia, the apo E4 allele frequency was significantly higher than normal (20.0% vs 10.3%, p < 0.005). Apo E3 was the most common isoform in normal and diabetic subjects and apo E2 isoform was rather low frequency compared to Caucasians. This pattern is similar to the Japanese population but somewhat different from other populations. From the data of a high association of apo E4 allele and cardiovascular disease with hypercholesterolemia, apo E isoform may be one of the determinants of hyperlipoproteinemia. The PCR method may be useful in apo E genotyping.
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PMID:Apolipoprotein E genotypes of normal and hyperlipidemic subjects. 819 63

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretion, and increased insulin gene expression but impaired glucose-stimulated insulin secretion. We suggest that after several weeks' duration, insulin resistance is accompanied by enhanced islet sensitivity to cholinergic activation and exaggerated insulin gene expression, whereas the failing islet sensitivity to glucose represents decompensation.
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PMID:Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice. 900 77

The low molecular weight (LMW) apolipoprotein of apo C plays an important role in the metabolism of triglyceride-rich lipoproteins. This study aimed at a characterization of the major LMW apolipoproteins from normal quail strain, and also from LAP (hyperlipidemia atherosclerosis-prone) strain to identify its genetic disorder. The major LMW apoprotein cDNA clone from normal quail comprised of approximately 500 bp, and encoded polypeptide of 78 amino acid residues containing 57 amino acids as a mature apolipoprotein. Although the quail LMW apoprotein showed a low homology to either apo C-I, C-II, or C-III of other animals, it retained a well-developed amphipathic alpha-helix structure. There was no difference in the deduced primary structure of the quail LMW apoprotein between LAP and normal strain. An analysis of the mRNA expression showed that the quail LMW apoprotein was only expressed in the liver of both LAP and normal Japanese quail. No difference was noted in the hepatic expression of the quail LMW apoprotein mRNA between normal and LAP strains with neither normal nor atherogenic dietary conditions. The structure and expression of the major LMW apoprotein thus had no relevance to higher susceptibility of LAP strain to the experimental atherosclerosis.
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PMID:The major low molecular weight apolipoprotein from normal and hyperlipidemia atherosclerosis-prone (LAP) Japanese quail. 1066 66

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

The glucagon-like peptides (GLP-1 and GLP-2) are processed from the proglucagon polypeptide and secreted in equimolar amounts but have opposite effects on chylomicron (CM) production, with GLP-1 significantly reducing and GLP-2 increasing postprandial chylomicronemia. In the current study, we evaluated the apparent paradoxical roles of GLP-1 and GLP-2 under physiological conditions in the Syrian golden hamster, a model with close similarity to humans in terms of lipoprotein metabolism. A short (30-min) intravenous infusion of GLP-2 resulted in a marked increase in postprandial apolipoprotein B48 (apoB48) and triglyceride (TG) levels in the TG-rich lipoprotein (TRL) fraction, whereas GLP-1 infusion decreased lipid absorption and levels of TRL-TG and apoB48. GLP-1 and GLP-2 coinfusion resulted in net increased lipid absorption and an increase in TRL-TG and apoB48. However, prolonged (120-min) coinfusion of GLP-1 and GLP-2 decreased postprandial lipemia. Blocking dipeptidyl peptidase-4 activity resulted in decreased postprandial lipemia. Interestingly, fructose-fed, insulin-resistant hamsters showed a more pronounced response, including possible hypersensitivity to GLP-2 or reduced sensitivity to GLP-1. In conclusion, under normal physiological conditions, the actions of GLP-2 predominate; however, when GLP-1 activity is sustained, the hypolipidemic action of GLP-1 predominates. Pharmacological inhibition of GLP-1 degradation tips the balance toward an inhibitory effect on intestinal production of atherogenic CM particles.
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PMID:GLP-1 and GLP-2 as yin and yang of intestinal lipoprotein production: evidence for predominance of GLP-2-stimulated postprandial lipemia in normal and insulin-resistant states. 2334 38

Atorvastatin, as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a widely prescribed medication for the treatment of dyslipidemia. However, despite its clinical efficacy in reducing major cardiovascular events, a wide inter-individual variability in its response exists. Several studies in this area point to the effect of polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene encoding the multiple organic anion-transporting polypeptide 1B1 (OATP1B1) involved in hepatic uptake of atorvastatin. Hence, the aim of this study was to analyze the association between the SLCO1B1 c.388A>G, c.521T>C, c.571T>C, c.597C>T, c.1086C>T, c.1463G>C and c.*439T>G polymorphisms and lipid-lowering effect and safety of atorvastatin. A hundred and fifty six patients with hyperlipidemia IIa and IIb, all of Macedonian origin, were included in the study receiving atorvastatin 20 - 80 mg/day for 3 months. SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped using the TaqMan allelic discrimination assay. As parameters of atorvastatin response, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A (ApoAI), apolipoprotein B (ApoB), lipoprotein(a) (Lp(a)), creatine phosphokinase (CPK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, using standard laboratory methods, at baseline and after 3 months of treatment. No statistically significant association between the different SLCO1B1 SNPs and atorvastatin response was observed. However, the carriers of c.521CC manifested a lower decrease in plasma levels of TG, TC, LDL-C and Lp(a), with percentage difference being 16%, 7%, 29% and 149%, respectively, compared to the carriers of c.521TT variant. Lower increase in HDL-C (271%) and ApoAI (293%) and higher increase in CPK (69%) in c.521CC carriers were also observed, confirming the lower OATP1B1 activity in carriers of the variant c.521 C allele. Similar results were obtained when a comparison between the percentage of biochemical parameter change was made between *15/*16/*17 heterozygotes and *15/*16/*17 non-carriers. The lack of a statistically significant association between the SLCO1B1 polymorphism and atorvastatin response can be explained dominantly by the low number of individuals homozygous for the rare c.521C variant allele. Despite this limitation, the study offers valuable information on the influence of the genetic determinant SLCO1B1 on atorvastatin response in the Macedonian population.
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PMID:Influence of SLCO1B1 polymorphisms on atorvastatin efficacy and safety in Macedonian subjects. 2944 75


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