Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the accumulation of lipid in macrophages is a characteristic feature of atherosclerosis, the mechanisms by which this lipid accumulation occurs have been intensively studied. This paper reviews the receptor- and non-receptor-mediated pathways that promote lipid accumulation in macrophages. Particular emphasis is placed on the contributions of two secretory products of macrophages, lipoprotein lipase and apolipoprotein E, to both receptor- and non-receptor-mediated uptake of triglyceride-rich lipoproteins by macrophages. The hormonal, lipid, and immunological factors that regulate the secretion of LpL and apoE by macrophages are discussed, as are how changes in the secretion of apoE and LpL that can modulate the uptake of triglyceride-rich lipoproteins by macrophages might influence the atherosclerotic process in people with diabetes.
Diabetes 1992 Oct
PMID:Role of lipoprotein lipase and apolipoprotein E secretion by macrophages in modulating lipoprotein uptake. Possible role in acceleration of atherosclerosis in diabetes. 152 41

Using two different techniques, phenotyping and genotyping, we have studied allelic variation at amino acids 112 and 158 of the apolipoprotein E gene locus in 52 patients with insulin-dependent diabetes and in 58 non-diabetic controls. Phenotypes were determined by isoelectric focusing and immunoblotting of delipidated, neuraminidase-treated plasma. Genotypes were determined by using the polymerase chain reaction to amplify a 227 base pair fragment of the apolipoprotein E gene spanning both allelic sites. This was then digested with the restriction endonuclease CfoI and the alleles identified by polyacrylamide gel electrophoresis. Discrepancies between phenotype and genotype were observed in 16 (15%) of the individuals studied, 7 (13%) in the diabetics and 9 (17%) in the controls. From these results it is concluded that isoelectric focusing can lead to the erroneous assignment of apolipoprotein E phenotype even after pretreatment with neuraminidase. It is suggested that genotyping by DNA analysis is the method of choice in determining apolipoprotein E status.
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PMID:Apolipoprotein E phenotyping: a word of caution. 177 11

We examined apolipoprotein E (apo E) allele frequencies in non-insulin-dependent diabetes mellitus (NIDDM) patients with normolipidemia or various types of hypertriglyceridemia to elucidate the association of the apo E alleles with hypertriglyceridemia in NIDDM. NIDDM patients with normolipidemia (N = 134) or hypertriglyceridemia [type IIb hyperlipoproteinemia (HLP) (N = 42), III HLP (N = 7), IV HLP (N = 96), and V HLP (N = 8)] were randomly selected from our Diabetic Clinics. Apo E phenotypes (genotypes) were determined by our rapid flat-gel isoelectric focusing method. The frequency of the epsilon 4 allele was significantly higher in the type IIb (20.2%, P less than .01) and V (25.0%, P less than .05) HLP patients than in the normolipidemic patients (8.9%), whereas the frequency of the epsilon 3 allele was significantly (P less than .025) lower in the type IIb HLP patients (78.6%) than in the normolipidemic patients (89.2%). The frequency of the epsilon 2 allele was significantly higher in the type III (64.3%, P less than .001) and IV (5.2%, P less than .05) HLP patients than in the normolipidemic patients (1.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type III (28.6%, P less than .001) and IV (82.8%, P less than .05) HLP patients than in the normolipidemic patients. Thus, it has proven that the epsilon 2 allele is related to type III and IV HLP in NIDDM, whereas the epsilon 4 allele is related to type IIb and V HLP in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein E allele frequencies in non-insulin-dependent diabetes mellitus with hypertriglyceridemia (type IIb, III, IV, and V hyperlipoproteinemia). 186 26

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.
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PMID:Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins in angiographically assessed coronary heart disease. 194 27

We typed 254 non-insulin-dependent diabetic (NIDDM) Mexican Americans living in Starr County, Texas, for the three common apolipoprotein E (apoE) alleles. Typing was performed via DNA amplification and Hha I restriction. The allele frequencies (epsilon 2 = 0.041, epsilon 3 = 0.860, epsilon 4 = 0.099) were in Hardy-Weinberg equilibrium (chi 2 = 0.60, df = 3) and did not differ from a random sample from the same population (chi 2 = 0.16, df = 2). Analysis of variance was used to test for mean differences in lipid, lipoprotein, and glucose levels among apoE types. Significant differences among types were detected for low-density lipoprotein cholesterol (LDL-chol; P = 0.042, R2 = 2.6) and beta-lipoprotein cholesterol (P = 0.019, R2 = 3.3) levels. Mean LDL-chol in E2/3 individuals was 2.69 mM, E3/3 was 3.26 mM, and E4/3 was 3.36 mM. Mean beta-lipoprotein cholesterol in E2/3 individuals was 3.05 mM, E3/3 was 3.64 mM, and E4/3 was 3.67 mM. Based on these results, we conclude that the effects of the apoE polymorphism on lipid profiles and glucose levels are the same in NIDDM subjects as in nondiabetic Mexican Americans and other populations. Other studies investigating the role of apoE polymorphism in diabetic subjects have found increased triglyceride levels in individuals possessing an epsilon 2-allele and an increased frequency of the epsilon 2-allele in hyperlipidemic diabetic subjects. We found no significant difference in mean triglyceride levels among genotypes. Possible reasons for this discrepancy are discussed, including DNA- versus protein-typing methods.
Diabetes 1991 Mar
PMID:Frequency and effects of apolipoprotein E polymorphism in Mexican-American NIDDM subjects. 199 75

Complement component 3 (C3) phenotype and allele frequencies were defined in 312 patients with type-1 diabetes (insulin-dependent diabetes mellitus), 256 patients with type-2 diabetes (non-insulin-dependent diabetes mellitus), 114 apparently non-diabetic first-degree relatives of type-1 diabetics, in 10 families (29 members) with a familial history of type-1 or type-2 diabetes, in 181 patients with coronary heart disease and 255 subjects with arterial hypertension. 512 blood donors served as controls. All persons investigated were Europeans. There is no evidence that genes linked to C3 influence susceptibility to type-1 and type-2 diabetes and to their late complications as well as to atherosclerosis and essential hypertension. The distribution of apolipoprotein E phenotypes in patients and controls was likewise not significantly different. The combined evaluation of data from linked genes (C3 and apo E) could not improve the results. Deductions of C3 as a genetic disease marker have to be interpreted with caution.
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PMID:Complement component 3 (C3) genetics and diabetes mellitus. 209 95

Hypercholesterolemia and increased concentrations of an apolipoprotein E (apoE)-containing HDL subclass, high density lipoprotein1 (HDL1) have been observed in streptozocin-alloxan diabetic dogs consuming normal amounts of dietary cholesterol. The aim of this study was to characterize the response of HDL1 and its targeting ligand, apoE, to insulin and HMG-CoA reductase inhibitor treatment in pancreatectomized diabetic dogs. Following induction of diabetes, plasma total cholesterol, HDL1, and apoE concentrations were all increased. Urinary mevalonate excretion, an index of cholesterol synthesis in humans, was 6-fold that of nondiabetic controls. Lipoprotein fractionation by Pevikon block electrophoresis and gel filtration chromatography showed that the increased cholesterol and apoE were associated with alpha 2-migrating particles corresponding to HDL1. Insulin treatment, resulting in near normal fasting blood glucose concentrations in the group as a whole (average 5.1 mM, 92 mg/dl), led to variable reductions in apoE, total plasma cholesterol, and HDL1. Uncorrected dyslipidemia during intensified insulin treatment appeared to be related to failure to achieve euglycemia. Despite unremitting hyperglycemia, treatment with lovastatin resulted in pronounced decreases in plasma cholesterol, HDL1 and apoE to concentrations below those observed in nondiabetic animals. Mevalonate excretion also fell, but remained twice normal. Thus neither modality corrected all of the abnormalities in canine diabetic dyslipidemia. Since apoE-containing HDL1 may mediate cholesterol traffic between the periphery and the liver (reverse cholesterol transport), the present observations suggest that increased cholesterol synthesis is accompanied by parallel abnormalities in cholesterol flux through the reverse transport pathway in the canine model.
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PMID:Plasma apolipoprotein E, high density lipoprotein1 (HDL1) and urinary mevalonate excretion in pancreatectomized diabetic dogs: effects of insulin and lovastatin. 224 16

Lipoprotein metabolism was studied by analyses of apolipoproteins, cholesterol content in lipoproteins and electrophoresis. The findings obtained suggested that the apolipoprotein levels such as A1 and B are related with particle number of lipoproteins such as HDL and LDL, while cholesterol content in lipoproteins is affected by qualitative change in particles as well. In patients with diabetes mellitus (NIDDM), LDL cholesterol correlated with HbA1c, and cholesterol and apolipoprotein B in the beta-area on electrophoresis showed accelerated mobilities, which were mimicked by in vitro glycation of LDL. In coronary heart diseases, elevation of apolipoprotein B and a low level of HDL cholesterol were general findings. The B/A1 ratio could be a sensitive indicator for these diseases. Hyper HDL cholesterolemias, excluding the patients with prostatic cancer who had undergone estrogen-treatment, showed elevated levels of apolipoprotein E in alpha 2-area on electrophoresis. Heterogeneity in Hyper HDL cholesterolemia was implicated. Qualitative analysis of lipoproteins by our method is believed to be useful.
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PMID:[Lipoprotein metabolism analysis in arteriosclerotic diseases]. 226 73

Lipids are transported in the blood in four major classes of lipoproteins. The triacylglycerol-rich lipoproteins are chylomicrons and very-low-density lipoproteins (VLDL) which are produced by the small intestine and liver, respectively. These lipoproteins mainly carry fatty acids to adipose tissue and muscle where the triacylglycerol is hydrolysed by lipoprotein lipase. The resulting particles that remain in the blood are chylomicron remnants and low-density lipoprotein (LDL), respectively. The remnant is taken up by the liver via endocytosis which is mediated by a specific receptor for apolipoprotein E (apoE). LDL, which are rich in cholesterol, can also be taken up by the liver or extrahepatic tissues by a receptor-mediated endocytosis that specifically recognises apoB or apoE. 'Nascent' high-density lipoprotein (HDL) particles are secreted by the liver and intestine and then undergo modification to become HDL3 and then HDL2 as they acquire cholesterol ester. They facilitate the reverse transport of cholesterol back to the liver. Little is known of the hormonal regulation of lipoprotein uptake by the liver. Recently, we have shown that insulin and tri-iodothyronine (T3) increase the specific binding of LDL to cultured hepatocytes whereas dexamethasone (a synthetic glucocorticoid) has the opposite effect. The changes in binding produced by insulin and dexamethasone are paralleled by alterations in the rate of degradation of apoB. These findings may in part explain the hypercholesterolaemia and increased risk of premature atherosclerosis that can be associated with poorly controlled diabetes or hypothyroidism.
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PMID:The biochemistry of lipoproteins. 314 85

Phenotypic expressions of apolipoprotein E (apo E) were studied in 94 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in 91 normal controls. The apo E gene frequencies observed in patients with NIDDM (epsilon 4, 0.101; epsilon 3, 0.824; and epsilon 2, 0.075) were not significantly different from those in normal controls (epsilon 4, 0.093; epsilon 3, 0.863; and epsilon 2, 0.044). Subgrouping the diabetic patients with and without hyperlipidemia, the epsilon 2 allele was significantly more frequent in patients with hypertriglyceridemia. The levels of serum triglyceride, very low density lipoprotein-cholesterol (VLDL-C), and VLDL-triglyceride (VLDL-TG) were significantly higher in patients with the epsilon 2 heterozygote than in those without the epsilon 2 allele (P less than .01). The results suggest that variation in the apo E gene may be one factor related to the hypertriglyceridemia present in patients with NIDDM.
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PMID:Phenotypes of apolipoprotein E and abnormalities in lipid metabolism in patients with non-insulin-dependent diabetes mellitus. 319


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