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

The prevalence of mild and moderate hypercholesterolemia among the middle-aged population of the G.D.R. is about 30%. Thus, this is the most important risk factor for coronary heart diseases. Primary therapeutic techniques are elimination of overweight, low-fat diet, rich in monoenic and polyenic acids, and increase of physical activity. When by these measures a decrease of cholesterol to 5.2-5.5 mmol/l is not achieved the introduction of lipid drugs is to be considered in dependence on the individual risk (associated risk factors like smoking, hypertension, diabetes, low HDL-cholesterol). In case of mild to moderate polygenic hypercholesterolemia cholestyramine, nicotinic acid and modern fibrates have the priority. Familial hypercholesterolemia demands as a rule the introduction of statins (e.g. lovastatin) or combinations of the above mentioned lipid drugs or the combination of cholestyramine and lovastatin, resp. In this way the prognosis even of patients with severe familial hypercholesterolemia can be improved decisively. Considering the fact that this would be a life-accompanying therapy a thorough consideration of the risk/benefit ratio and an adequate medical supervision are necessary.
 ...
PMID:[Guidelines for the treatment of hypercholesterolemia]. 224 95

Rat hepatocytes were preincubated for 16 h with hormones or drugs and then for a further 8 h with 125I-human low-density lipoprotein (LDL). Glucagon (via cyclic AMP) and adrenaline (via cyclic AMP and alpha-effects) increased the binding of 125I-LDL to the LDL receptor, and the degradation of LDL to [125I]iodotyrosine. The effects on degradation were antagonized by dexamethasone, and the action of cyclic AMP on binding and degradation was inhibited by actinomycin D. The results are discussed in relation to the control of lipoprotein metabolism in diabetes.
 ...
PMID:Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes. 255 96

Ultrasound methods have been used for the vascular examination of middle-aged patients with insulin-dependent diabetes mellitus (IDDM, n = 44) or heterozygous familial hypercholesterolemia (FH, n = 37); they were compared with 50 healthy controls. To define the localization of the early arterial lesions in these two conditions, the determination of ankle pressure by Doppler ultrasound and the detection of flow disturbances in the iliac arteries by echo-Doppler technique have been combined in a single vascular investigation. There were no major differences in mean age, degree of overweight, sex distribution, blood pressure, or smoking habits among the three groups. Total serum cholesterol in patients with FH was almost double compared with diabetics and controls. Triglyceride, HDL cholesterol, and blood pressure values did not differ. Nine of 88 limbs of patients with IDDM had an abnormally low ankle-arm pressure ratio (less than 0.97), and there were three cases of low ratio of 100 limbs in the control subjects (P less than .02). The corresponding figure for heterozygous FH was of three of 74 limbs (not different from controls). Echo-Doppler abnormalities suggesting lesions in the iliac arteries were significantly increased (P less than .01) in FH patients (13 limbs with lesions of 74) compared with controls (four of 100 limbs). The proportion of echo-Doppler abnormalities in IDDM (four of 88 limbs) was practically the same as compared to the controls.
 ...
PMID:Different localization of early arterial lesions in insulin-dependent diabetes mellitus and in familial hypercholesterolemia. 267 11

Glucose can react with the lysine residues of low-density lipoproteins (LDLs) and convert the lipoprotein to a form with a receptor-mediated uptake by cultured cells that is impaired. However, in contrast to other modified lipoproteins taken up by both murine and human macrophages via the scavenger-receptor pathway that may induce the formation of foam cells, glycosylated LDL is not recognized by murine macrophages, and thus far, it has not been shown to lead to marked intracellular accumulation of cholesterol in human macrophages. This study illustrates that glycosylated LDL incubated with human monocyte-derived macrophages, at a concentration of 100 micrograms LDL/ml medium, stimulates significantly more cholesteryl ester (CE) synthesis than does control LDL (10.65 +/- 1.5 vs. 4.8 +/- 0.13 nmol.mg-1 cell protein.20 h-1; P less than .05). At LDL concentrations similar to those of plasma, the rate of CE synthesis in macrophages incubated with glycosylated LDL is more markedly enhanced than that observed in cells incubated with control LDL (3-fold increase). The marked stimulation of CE synthesis in human macrophages exposed to glycosylated LDL is paralleled by a significant increase in CE accumulation in these cells (P less than .001). The increase in CE synthesis and accumulation seem to be mediated by an increase in the degradation of glycosylated LDL by human macrophages. Glycosylated LDL enters the macrophages and is degraded by the classic LDL-receptor pathway in slightly smaller amounts than control LDL, but its degradation by pathways other than the classic LDL receptor or scavenger receptor is markedly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 May
PMID:Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocyte-derived macrophages. 312 28

The purpose of this study was to elucidate the relationship between two genetic factors associated with raised blood cholesterol, i.e. familial hypercholesterolemia (FH) and apolipoprotein (apo) E4. A group of 50 unrelated heterozygous FH patients aged 33-71 years were studied together with 129 normolipidemic subjects. A significantly higher frequency of apo E4 phenotypes was found in FH patients (30.0%) than in normolipidemic subjects (15.5%). FH patients were divided into two groups with and without apo E4. Plasma total cholesterol (Chol) and triglyceride (TG) levels were significantly higher, and plasma low density lipoprotein-cholesterol (LDL-Chol) level tended to be higher in FH patients with apo E4 than in those without apo E4. In addition, the prevalence of ischemic heart disease (IHD) was significantly higher in FH patients with apo E4 (73.3%) than in those without apo E4 (31.4%). No significant difference was noted in age and in the prevalence of obesity, diabetes, hypertension and smoking between the FH groups with and without apo E4. These results suggest that apo E4 is associated with higher levels of total Chol and TG and, at least in part, contributes to the predisposition to IHD in FH.
 ...
PMID:Familial hypercholesterolemia and apolipoprotein E4. 321 64

We followed 54 subjects with heterozygous familial hypercholesterolemia for an average of 10 (range 3-14) years. Half were treated surgically with partial ileal bypass and the other half (matched for age, sex, coronary heart disease, blood pressure, diabetes mellitus, smoking, obesity, and serum cholesterol concentration) were treated conservatively with diet and hypolipidemic drugs. The mean decrease in serum cholesterol concentration from the average value of 522 mg/dl on entry into the study was 32% in the surgically treated group and 10% in the conservatively treated group. One quarter of the subjects (14 of 54) had symptomatic cerebrovascular disorders and one tenth (six of 54) suffered a brain infarction at a mean age of 43 (range 30-57) years. Two thirds of the brain infarctions occurred during follow-up. The method of treatment of familial hypercholesterolemia did not affect the number of new cerebrovascular events. The incidence of brain infarction was 7.4/1000/yr. The risk of brain infarction in these subjects with familial hypercholesterolemia was at least 20 times higher than in the general population. We conclude that symptomatic subjects with familial hypercholesterolemia have not only a high risk of coronary heart disease but also a high risk of cerebrovascular disorders.
 ...
PMID:Risk of brain infarction in familial hypercholesterolemia. 341 6

This review discusses the genetic factors in the development of arteriosclerosis and coronary heart disease (CHD). In several studies, multivariate analysis of prospective mortality/morbidity data and angiographic findings have indicated that a family history of CHD contributed to CHD risk independently of the established risk factors. In addition, ethnic groups that differ in the prevalence and incidence of CHD also markedly differ in blood groups and protein-enzymatic markers. These or other genetic differences may affect CHD rates. Data from fraternal and identical twins, the source of some early genetic CHD findings, are reviewed. Genetic disorders of lipoprotein metabolism and transport, such as familial hypercholesterolemia, as well as other monogenic disorders are discussed. The role of apoprotein E polymorphism i other monogenic disorders are discussed. The role of apoprotein E polymorphism in determining plasma LDL variability among individuals is considered. Recombinant DNA technology, molecular cloning, and the identification of restriction fragment length polymorphisms are new tools for investigators who assess DNA polymorphism. Recent advances in that domain include: DNA polymorphisms affecting blood levels of apo A-I and A-II, association of a DNA insertion on chromosome 19 with severe premature atherosclerosis, and information concerning linkage of the genes for various apolipoproteins. In addition, the evidence for a major genetic component in diabetes mellitus and research into the genetic aspects of hypertension are reviewed. The male/female ratio in pathologically and epidemiologically assessed atherosclerosis may provide clues to the role of genetics. Early structural changes in the coronary artery intima are compatible with the ethnic and gender predilection. A key question in understanding underlying mechanisms in atherosclerosis is why coronary arteries are occluded in individuals whose other arterial systems are largely unaffected. The review concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on uncovering genetically determined differences in arterial wall response to blood flow. Subpopulations with different genetic risks may be identified, in which case universal preventive strategies might be replaced with specific ones.
 ...
PMID:Genetic aspects of arteriosclerosis. 352 20

Low density lipoprotein (LDL) is probably the most atherogenic of all the lipoproteins. Several abnormalities in LDL metabolism seem to be associated with coronary heart disease (CHD) one of them being an elevation of plasma LDL concentration. Recent findings suggest that disorders in the metabolism of LDL could be associated with accelerated atherosclerosis even without elevated LDL levels such as increased flux of LDL and changes in the LDL composition. Elevation of plasma LDL levels can be caused by two factors, first, a decrease in the clearance of LDL and second, an overproduction of this lipoprotein. Catabolism of LDL is largely determined by the LDL receptors as clearly shown in patients with familial hypercholesterolemia (FH). In this inherited disease the patients do not have normal LDL receptors and their LDL levels are remarkably elevated. LDL production is also increased in these subjects. In the rest of the population LDL levels are regulated by both the LDL clearance and production rate. The latter also seems to be related to the LDL receptor activity. The conversion of the LDL precursor, very low density lipoprotein (VLDL) to LDL is the most important factor regulating LDL synthesis. When the LDL receptor activity is low a large fraction of VLDL apolipoprotein B (apoB), the major structural protein in VLDL, is converted to LDL, and LDL production is high. On the other hand, only a small part of VLDL apoB is converted to LDL resulting in low LDL synthesis rate in conditions with high LDL receptor activity. The relationships between production and clearance of LDL are, however, more complex. There are individuals who produce a large number of VLDL and LDL particles but maintain LDL concentrations at a normal level by clearing their LDL very effectively. These subjects obviously have another abnormality in lipoprotein metabolism namely an overproduction of apoB. This disorder has been observed in several conditions like obesity, adult-onset diabetes mellitus, several patients with familial combined hyperlipidemia and some normolipidemic subjects with premature coronary heart disease. In all these conditions increased transport of LDL can be associated with coronary artery disease even in the absence of hypercholesterolemia. This raises the possibility that increased flux of LDL could itself be atherogenic possibly by overloading reverse cholesterol transport. Finally, there is some evidence that LDL particle composition may be important in the process of atherogenesis. High LDL apoB but normal LDL cholesterol levels, hyperapobetalipoproteinemia, has been associated with premature coronary heart disease.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Abnormalities in metabolism of low density lipoproteins associated with coronary heart disease. 390 93

To test whether triglyceride-enriched low-density lipoprotein (LDL) obtained from subjects with diabetic hypertriglyceridemia is metabolized normally by cells, LDL was separated from seven healthy control subjects (fasting plasma glucose [FPG] 91 +/- 10 mg/dl [mean +/- SD], triglyceride [TG] 110 +/- 47 mg/dl), six diabetic normolipidemic patients (FPG 218 +/- 65 mg/dl; TG 139 +/- 75 mg/dl), six diabetic hypertriglyceridemic patients (FPG 214 +/- 71 mg/dl; TG 1915 +/- 1680 mg/dl), and five nondiabetic hypertriglyceridemic patients (FPG 92 +/- 8 mg/dl; TG 2013 +/- 1889 mg/dl). Binding of 125I-labeled LDL from hypertriglyceridemic subjects with and without diabetes to cultured skin fibroblasts was significantly decreased to 74 +/- 19% and 78 +/- 14% of that seen with LDL from normolipidemic nondiabetic subjects and diabetic normolipidemic controls (100 +/- 0%, 101 +/- 25%; P less than 0.005). Unlabeled LDL from hypertriglyceridemic subjects with and without diabetes failed to suppress LDL receptor activity and sterol synthesis from 14C-acetate as efficiently as unlabeled LDL from healthy subjects. The ability of LDL from hypertriglyceridemic subjects, whether diabetic or not, to suppress LDL binding was inversely related to the ratio of triglyceride to protein in LDL (r = 0.71, P less than 0.01) and showed a positive correlation with the LDL cholesterol/protein ratio (0.69, P less than 0.01). Thus, LDL from patients with hypertriglyceridemia, with or without coexistent diabetes, shows impaired binding to LDL receptors and less ability to downregulate LDL receptor activity and sterol synthesis than does LDL from normolipidemic diabetic and nondiabetic subjects. These findings suggest that factors associated with hypertriglyceridemia rather than with diabetes result in altered metabolism of LDL in these disorders.
Diabetes 1985 Jan
PMID:Metabolism of low-density lipoprotein from patients with diabetic hypertriglyceridemia by cultured human skin fibroblasts. 396 57

In normal individuals, insulin regulates lipoprotein metabolism. It increases hepatic triglycerides (TG) secretion and makes VLDL and chylomicrons post prandial removal easy by stimulating adipose tissue lipoprotein lipase (LPL). Insulin activity and cholesterol rich lipoprotein is more complicated: by its action on VLDL and chylomicrons turn-over, it influences LDL and HDL formation. It regulates cellular cholesterol pool at different levels: stimulation of LDL receptor, but also of HMG CoA reductase. Controlling LCAT, in participates in cholesterol removal by HDL. In insulin dependent diabetes, lack of adipose tissue LPL stimulation augments triglycerid-rich lipoproteins, by slowing their catabolism, resulting in a weak increase of LDL and a lowering of HDL. In non insulin dependent diabetes with hyperinsulinism, VLDL are elevated because of insulin stimulation of triglycerid hepatic production. LDL are increasing. HDL status remains discussed: HDL cholesterol is low but HDL triglycerid is high, there is no known disturbance of apo A level. In the two types of diabetes, although mechanism is different, perturbation of lipoprotein metabolism may account for the atherogenicity of this disorders.
 ...
PMID:[Insulin and the metabolism of lipoproteins]. 634 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>