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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent ) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35x-1.22, r = 0.90, P less than 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 +/- 0.42% of added LDL/10(6) cells and 1.34 +/- 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation mediu. Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes.
Diabetes 1979 Oct
PMID:Low density lipoprotein receptor activity in fibroblasts cultured from diabetic donors. 22 33

The following pathogenetic mechanisms, exemplified by three diseases (diabetes mellitus, hyperthyroidism and familial hypercholesterolemia), are discussed: 1. The impaired interaction between a chemical signal and a specific receptor can be the cause of a disease. 2. The cause for an imparied interaction can be a defect of the receptor, i.e., a reduced number of receptors or an altered receptor affinity, or a wrong signal. 3. A defect of the receptor can be induced by exogenous influences or it can be determined genetically. 4. The receptor and the signal can be modified by their interaction: the number of receptors is reduced by high concentrations of the chemical signal or by increased degradation due to binding to the receptor. 5. The receptor concept opens new perspectives for the pathogenetic understanding, diagnosis and therapy of some diseases.
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PMID:[Cell receptor defects as the cause of endocrine and metabolic diseases (author's transl)]. 38 68

In 275 neonates mean cord blood cholesterol level was 70 +/- 17 (SD) mg/dl, with a range from 30 to 153 mg/dl. Mean cord blood triglyceride level was 33 +/- 26 (SD) mg/dl, with a range of 5-192 mg/dl. In an attempt to correlate perinatal problems and hypercholesterolemia in neonates we compared 15 hypercholesterolemic neonates who had cord blood cholesterol levels above 95 mg/dl, range 100-153 mg/dl, and triglyceride levels less than 65 mg/dl, with 65 normal neonates whose cord blood cholesterol levels were less than 95 mg/dl and triglyceride values were less than 65 mg/dl. We also compared 19 hypertriglyceridemic neonates who had cord blood triglyceride levels greater than 65 mg/dl, range 66-192 mg/dl, and cholesterol levels less than 95 mg/dl with the 65 normal neonates. Elevated cord blood cholesterol values greater than 95 mg/dl or triglyceride values greater than 65 mg/dl were associated with maternal-fetal problems related to unfavorable intralterine environment, fetal distress, and fetal anoxia. There was a significant correlation between post-term delivery and hypercholesterolemic neonates, and low Apgar scores and maternal hypertension were more often associated with hypertriglyceridemic infants. There was no association between serum cholesterol or triglyceride levels and prolonged ruptured membranes, cesarean section, maternal diabetes, or maternal hypothyroidism. Consequently, we think that when neonates are identified who have elevated cholesterol or triglyceride levels, the possible influence of maternal-fetal perinatal complications should be considered. Speculation Infants with familial hypercholesterolemia may be identified by increases in cord blood cholesterol concentrations. Elevated cord blood cholesterol or triglyceride values of some neonates, however, may represent hyperlipoproteinemia related to neonatal stress associated with maternal-fetal perinatal problems.
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PMID:Cord blood hyperlipoproteinemia and perinatal stress. 83 Dec 15

Dietary lipid, following incorporation into chylomicrons, is rapidly removed from the blood by a two-stage process. Most of the triglyceride is taken up by extrahepatic tissue, particularly muscle and adipose tissue. The residual triglyceride and virtually all of the cholesterol ester is removed by the liver through the clearance of a particle called a chylomicron remnant. The remarkable rapidity and specificity of uptake of this particle seems to be due to its acquisition of apoE in the plasma. Uptake is mediated in part by the LDL receptor, the LRP (alpha a-macroglobulin receptor), and perhaps by a sieving mechanism that leads to trapping, but not endocytosis. Uptake is modulated by the type of apoE inherited, the amount of apoC present on the particle, and, perhaps, the phospholipid and fatty acyl chain composition of the particle. The process may be slowed in diabetes and hypothyroidism. The metabolic effects of the particle can be variable, depending on the composition of the diet, and this can affect whole body cholesterol metabolism significantly. Furthermore, even moderately prolonged residence of these particles in the circulation could contribute in a significant way to atherogenesis. Thus, the remnant particle and its uptake by the liver may be important links in determining the dietary contribution to the rate of atherosclerosis.
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PMID:Hepatic clearance of plasma chylomicron remnants. 133 75

In people with diabetes, glycation of apolipoproteins correlates with other indices of recent glycemic control, including HbA1. For several reasons, increased glycation of apolipoproteins may play a role in the accelerated development of atherosclerosis in diabetic patients. Recognition of glycated LDL by the classical LDL receptor is impaired, whereas its uptake by human monocyte-macrophages is enhanced. These alterations may contribute to hyperlipidemia and accelerated foam-cell formation, respectively. Glycation of LDL also enhances its capacity to stimulate platelet aggregation. The uptake of VLDL from diabetic patients by human monocyte-macrophages is enhanced. This enhancement may be due, at least in part, to increased glycation of its lipoproteins. Glycation of HDL impairs its recognition by cells and reduces its effectiveness in reverse cholesterol transport. Glycation of apolipoproteins may also generate free radicals, increasing oxidative damage to the apolipoproteins themselves, the lipids in the particle core, and any neighboring macromolecules. This effect may be most significant in extravasated lipoproteins. In these, increased glycation promotes covalent binding to vascular structural proteins, and oxidative reactions may cause direct damage to the vessel wall. Glycoxidation, or browning, of sequestered lipoproteins may further enhance their atherogenicity. Finally, glycated or glycoxidized lipoproteins may be immunogenic, and lipoprotein-immune complexes are potent stimulators of foam-cell formation.
Diabetes 1992 Oct
PMID:Lipoprotein glycation and its metabolic consequences. 152 39

In earlier studies, we showed that incubation of HMM with LDL IC led to cellular CE accumulation and to the transformation of macrophages into foam cells. This study demonstrates that the stimulation of macrophages with RBC-LDL-IC also increases the uptake of native LDL, most likely because of an increased LDL receptor number, as shown by Scatchard plot analysis (x-axis intercept 1267 vs. 352 ng LDL/mg protein in control cells). To determine whether the increase in LDL-receptor activity was secondary to a decrease in the macrophage free (nonassociated) cholesterol content, we measured the T-UC and the UC associated with intracellular intact LDL and demonstrated that 50% of the T-UC is associated with intact LDL. UC not associated with LDL (free cholesterol) was lower in LDL-IC-stimulated cells than in control cells. These results suggest that UC associated with nondegraded intracellular LDL is nonregulatory, a conclusion that was also supported by finding increased sterol synthesis (192.8 +/- 22.9 pmol/mg protein vs. 94.8 +/- 11.8) in RBC-LDL-IC-stimulated macrophages. In conclusion, the uptake of RBC-LDL-IC by macrophages led to increased intracellular accumulation of CE and UC, to a decrease in the cell regulatory pool of free cholesterol, and to an increase in LDL-receptor activity.
Diabetes 1992 Oct
PMID:Lipoprotein-immune complexes and diabetic vascular complications. 152 44

Hyperlipidemia may play a role in the progression of diabetic and other renal diseases. Low density lipoprotein (LDL) and other proteins including extracellular matrix components undergo nonenzymatic glycation in vivo. We examined the effects of glycation of LDL as occurs in diabetes (4 to 8%) on binding and uptake by mesangial cells and their proliferation. The glycation of LDL (g-LDL) significantly decreased its binding and uptake by mesangial cells by 15 to 20%, indicating that glycated LDL binds to the LDL receptor, but with lower affinity than LDL. Both LDL and g-LDL modestly stimulated [3H] thymidine incorporation into mesangial cells at 5 to 10 micrograms/ml. Native, oxidized (Ox-LDL) and glycated LDL all bound to the extracellular matrix generated by rat mesangial cells in culture. The binding of LDL, Ox-LDL and g-LDL to mesangial matrix was two to four times higher than to mesangial cells. Binding of LDL and g-LDL was significantly higher to glycolaldehyde modified matrix, which serves as an in vitro model for nonenzymatic glycation end-product cross-linking of matrix which occurs in long-standing diabetes. Based on these findings, we propose that glycation of LDL decreases its binding and uptake by the LDL receptor of mesangial cells and may slow its catabolism. Furthermore, LDL bound to extracellular mesangial matrix can undergo oxidation and generate cytotoxic LDL components. This process may be further enhanced by advanced glycation of the mesangial matrix in diabetes, contributing to glomerular pathology.
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PMID:Interactions of LDL and modified LDL with mesangial cells and matrix. 161 32

Intercellular adhesion molecule-1 (ICAM-1) is an integral membrane protein, a member of the immunoglobulin superfamily, and a ligand for LFA-1, a beta 2 leukocyte integrin. ICAM-1 has a tissue distribution similar to that of the major histocompatibility complex class II antigens and is likely to play a role in inflammatory responses. We have mapped this gene to proximal mouse chromosome 9 by using mouse-hamster somatic cell hybrids and an interspecies backcross. Since human ICAM-1 maps to chromosome 19, it joins the LDL receptor to establish a new conserved syntenic segment between human chromosome 19 and proximal mouse chromosome 9. Murine Icam-1 maps between Cbl-2 and the centromere in the same region as one of the susceptibility genes for insulin-dependent diabetes mellitus (Idd-2) that is postulated to play a role in immune function and inflammation leading to insulitis. The mapping of Icam-1 to the region known to contain the Idd-2 gene raises the question of whether the phenotypic differences attributed to the Idd-2 locus might be due to genetic variation in Icam-1.
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PMID:Assignment of the gene for intercellular adhesion molecule-1 (Icam-1) to proximal mouse chromosome 9. 167

Compositional changes of apoproteins and lipids in lipoproteins influence their affinities for receptors and enzymes. Decrease of apo C proteins and increase of apo E in chylomicron and very low density lipoproteins (VLDL) during their catabolism might promote the binding to remnant receptor. On the other hand, the affinity for lipoprotein lipase (LPL) gradually decreases and that for hepatic lipase increases. However, the responsiveness of VLDL to LPL might be under the control of triglyceride (TG)/surface component ratios but not of the apoprotein ratios in ordinary circumstances judging from the results of the releases of fatty acids from VLDL by LPL in vitro. Responses of VLDL from diabetic patients to LPL significantly decreased compared with those from non-diabetic subjects. Glycation of VLDL in vitro impaired their responses to LPL. Therefore, delayed catabolism of VLDL in diabetes might partially depend upon glycation of VLDL besides the decreased LPL activity. Low density lipoproteins (LDL), apoproteins of which consist mostly of apo B protein and had a low TG level, showed a high affinity to the LDL receptor. However, LDL from hypertriglyceridemic subjects, in which the TG contents was increased, had a low affinity to the receptor. Since high density lipoproteins (HDL) from patients in acute phases contain a large amount of serum amyloid A protein (SAA), the percentages of apo A proteins markedly decreased. When SAA-rich HDL were incubated with leucocytes, SAA were degraded rapidly, although other apoproteins remained to be unchanged. Therefore, such HDL become unstable, and this might induce low HDL levels in the acute phase.
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PMID:[Metabolic disorders of lipoproteins--influences of compositional changes of lipoproteins upon their metabolic behavior]. 188 Sep 36

Coronary heart disease (CHD) is an imprecise, inappropriate monitor of atherosclerosis severity and by inapplicable extrapolation CHD risk factors are incorrectly assumed to be causes of atherosclerosis. Taking into account (1) the misuse and substantial diagnostic error of CHD, (2) errors in determining the prevalence of risk factors, (3) the use of a young non-representative minority of sufferers of CHD, (4) bias posed by inclusion of familial hypercholesterolemia (FH) in clinical studies and (5) mutual inter-relationships, genetic influence and age dependence of hypercholesterolemia, hypertension, diabetes mellitus and body mass or obesity, it is unlikely that multivariate statistical analyses can adequately differentiate between their effects. These factors are age dependent and so are CHD and atherosclerosis. The importance of hypercholesterolemia in atherogenesis is suspect particularly since the vascular pathology of familial hypercholesterolemia and of cholesterol-fed animals has been misrepresented and does not provide support for the role of hypercholesterolemia in atherogenesis.
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PMID:The epidemiological relationship of hypercholesterolemia, hypertension, diabetes mellitus and obesity to coronary heart disease and atherogenesis. 220 Aug 50


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