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)

Tests were set up on 59 albino male-rats with reproduced functional overstress and depletion of the insular system of the pancreas thorough a long-term (for 50, 100 days) peroral introduction of glucose (2 g/100 g body weight, every other day) and with and alloxan-induced diabetes (achieved by poisoning the animals with a 2.5% alloxan solution, 15 mg/100 g administered in a single dose intraperitoneally). A comparison of the data obtained ascertained the presence of a number of similar pathobiochemical changes in the metabolism, viz. hyperglycemia, an increase of the free cholesterol fraction, a diminution of the bound cholesterol fraction and a fall of the insulin-like activity (ILA) in the blood serum, a rise in glycogen and beta-lipoproteids in the liver; morphologically--a reduced count of Langerhan's islands beta-cells, less intensive colouration of the specific granulation in their cytoplasma manifestations of vacuolar and granular dystrophy of the liver. Further tests were staged on 23 rabbits involving a long-term introduction of glucose (in amounts of 25 g/kg every other day) and a cholesterol-induced atherosclerosis (by administering 0.2 g/kg of cholesterol in oil, daily), which also showed similar changes in the figures of the carbohydrate and fat-lipoids metabolism, such as hyperglycemia, an increased level of total lipids, cholesterol and its fractions, beta-lipoproteids, a fall of ILA in the blood serum, as well as variations in the morphological picture of the aortic wall. The above findings suggest that a protracted administration of glucose can produce both diabetogenic and atherogenic effects.
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PMID:[Diabetogenic and atherogenic effects of glucose]. 17 88

At present the two different mechanisms underlying the hypertriglyceridemia of diabetes are reasonably well defined. The rationale of therapy has grown from this knowledge. One form of hyperlipidemia is due to the hyperinsulinemia which results from the patient's resistance to insulin. The approach to treatment aims to overcome the insulin resistance. In most patients this is done by treating their obesity. The other form of hypertriglyceridemia results from insulin deficiency and is treated by bringing the patient's diabetes under control. There is strongly suggestive evidence that hypertriglyceridemia may be associated with a high risk of atherosclerosis. The reason for treating hypertriglyceridemia in general, and in the diabetic in particular, is to reduce this risk. However, it must be conceded that, at the moment, there is no information about the effect of lower triglyceride levels on the incidence of atherosclerosis. Hence much epidemiologic research is needed before our rationale for treatment can move from the realm of hope to the realm of definite proof. In the mean time an attack on this and the other risk factors is the best way we have to attempt to prevent the major complication of diabetes, atherosclerosis.
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PMID:Hyperlipidemia, atherosclerosis, and diabetes. 20 21

Lipoprotein cholesterol and triglyceride levels have been determined in normal and diabetic Pima Indian women aged 20-35, HDL cholesterol levels were lower, LDL cholesterol levels were higher, and the ratio of HDL cholesterol/LDL cholesterol, a reflection of lipoprotein cholesterol distribution, was lower in the diabetics compared to the normals. VLDL triglyceride levels were also elevated in the diabetics. An analysis of lipoprotein composition suggested that these changes primarily reflect changes in numbers of particles, since lipid composition and lipid/protein ratios were similar in lipoproteins isolated from normals and diabetics. The ratio of ester/free cholesterol in LDL and HDL was lower in normal Pima Indians than in a comparable group of Caucasians, although plasma LCAT activity was not significantly different. The data indicate that diabetes may be associated with shifts in distribution of LDL and HDL, as well as with increases in VLDL.
Atherosclerosis 1978 Jun
PMID:Lipoprotein composition in diabetes mellitus. 20 99

The aim of the present study was to determine whether skin fibroblasts derived from patients with ischemic heart disease (IHD), which could not be related to accepted risk factors, would show a metabolic abnormality with respect to lipid or lipoprotein metabolism. Male patients 30-52 years old suffering from IHD were subdivided into two groups: those in whom IHD was not associated with risk factors such as hypertension, hyperlipoproteinemia, diabetes or smoking (group I); and those in whom heavy smoking was the only major risk factor recognized (group II). The controls were patients with angiographically normal coronary arteries (group III). Skin fibroblasts obtained from these patients were cultured and investigated with respect to metabolism of low density lipoprotein (LDL), synthesis of cellular lipids and induction of cholesterol ester accumulation in the presence of chloroquine, an inhibitor of lysosomal hydrolases. After 24 h incubation, the uptake and degradation of LDL protein in cells from patients of group II was significantly higher than in the controls, group III, but not different from those of group I. Hydrolysis of [3H] cholesterol linoleate, and incorporation of [3H] oleic acid into total lipids and into cholesterol esters was similar in cell cultures of the 3 groups studied. After exposure to chloroquine and LDL, the cells from the different donors accumulated cholesterol ester to a similar extent. Thus, whereas no significant difference was encountered in the lipid and lipoprotein metabolism in cells of patients with IHD without risk factors and controls, some increase in LDL metabolism was seen in cells from patients with IHD and with a history of smoking. It remains to be determined whether this increase was causally related to smoking.
Atherosclerosis 1978 Jul
PMID:Study of cultured skin fibroblasts from patients with and without ischemic heart disease. Metabolism of low density lipoprotein and cholesterol ester, synthesis of cellular lipids and effect of chloroquine on accumulation of cholesterol ester. 20 2

Serum cholesterol-binding reserve (SCBR), the capacity of a serum sample to solubilize additional cholesterol in excess of its cholesterol content, was measured in 43 white male patients with maturity-onset diabetes in the age range of 35--59 years who were under treatment with insulin. The values were compared with those of 194 nondiabetic controls of the same race, sex, and age range. The mean +/- S.D. of SCBR of patients (71.9 +/- 29.3 mg./dl.) was lower than that of controls (88.9 +/- 30.9 mg./dl.) (p less than 0.001). Age in the range of 35 to 59 years had no correlation with SCBR in either patients or controls. SCBR was positively correlated with serum levels of cholesterol (SC) and triglycerides (TG) in both patients and controls. After adjustment for SC and TG, the difference in SCBR between patients and controls persisted (p less than 0.001). In 15 of 20 (75 per cent) patient-control pairs matched for SC and TG to within 5 per cent, the patient had lower SCBR (paired t-test, p less than 0.002). In 16 patients without elevation of serum lipid levels (SC below 250 and TG below 150 mg./dl.), the mean +/- S.D. of SCBR (59.1 +/- 17.7 mg./dl.) was lower than that of 49 controls having serum lipids in the same range (77.4 +/- 31.7 mg./dl.) (p less than 0.03). These results indicate an association of decreased SCBR with diabetes and are consistent with the hypothesis that low SCBR is associated with accelerated atherosclerosis and enhanced risk for coronary heart disease.
Diabetes Care
PMID:Decreased serum cholesterol-binding reserve in diabetes mellitus. 21 96

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

Despite the advances in therapy, the high incidence, high mortality, and prematurity of coronary heart disease demonstrate the need for prevention. Measurement of a series of easily determined risk factors permits the early recognition of subjects at risk with remarkable reliability. However, reduction of risk factors affords protection against the illness only if they are causally connected with the disease mechanisms. The major evidence for linking atherosclerosis and its consequences with risk factors is reviewed. Particular attention is focused on serum lipids and the "lipid theory", smoking, elevated blood pressure, and physical inactivity, which are, on the basis of current knowledge, not only the most important factors but those most readily influenced by changes in daily living habits. Among the multiple risk factors mention is also made of obesity, diabetes, psychosocial stress, and hereditary predisposition. The probability of a causal relationship between risk factors and disease mechanisms justifies every effort to prevent the development of these precursors, or to treat them prophylactically if already present.
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PMID:[Prevention of arteriosclerosis. Current basis]. 22 49

An analysis was made of correlative factors which might be related to the angiographically measured extent of coronary artery disease in 140 patients. All patients presented with clinically important chest pain. Thirty-three had a normal coronary arteriogram. The extent of the atheromatous process was measured precisely at angiography by three different techniques. A coronary score, based on the percentage of luminal narrowing, was found to be best suited for the analysis. The most important contributory factors to the severity of atherosclerosis was duration of clinical history, number of previous myocardial infarctions, and male sex, but more specifically elevation of serum cholesterol and diabetes mellitus. Cigarette smoking, obesity, hypertension, a family history of atherosclerosis, and elevated serum triglycerides had a positive influence but this was not statistically significant.
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PMID:Relationship between extent of coronary artery disease and correlative risk factors. 22 61

The proliferation of aortic smooth muscle cells (ASMC) of Wistar rats, impaired by risk factors such as arterial hypertension, diabetes mellitus, atherogenic diet and staphylolysin injections and of normal Wistar rats treated with antirheumatic drugs such as prednisolone and acetylsalicylic acid was investigated. The cells of these animals were cultivated, subcultivated, and in the 2nd subcultures the cell numbers/5 ml medium were counted by means of Coulter Counter, and the cells were incubated with [3H]thymidine and the percentage of labelling in 100 or 1000 counted cells was stated. The effect of risk factors such as LDL and staphylolysin and of antirheumatic drugs such as prednisolone, acetylsalicylic acid, D-penicillamine and chloroquine added to the 2nd subcultures of cultivated ASMC of normal minipigs was investigated by the same method. The proliferation of cultivated ASMC of rats impaired by risk factors was accelerated. The proliferation of cultivated ASMC of rats treated with antirheumatic drugs was inhibited. The proliferation of ASMC of minipigs in the 2nd subcultures was activated by addition of risk factors and inhibited by addition of antirheumatic drugs. Antirheumatic drugs given to the rats and added to the medium of the 2nd subcultures of ASMC of normal minipigs inhibit the acceleration of ASMC proliferation induced by simultaneously given risk factors. The proposal to augment up our arsenal of the hitherto existing preventive and therapeutical measures by the application of antirheumatic drugs based on the experimental models referred to is supported by the result of a limited prospective double-blind-study of a sample of 133 male patients after myocardial infarction. The most remarkable result that the acceleration of the ASMC proliferation, the real pathologic process of arteriosclerosis, is inhibited by the application of antirheumatic drugs, at exactly the same time as the acceleration of the fibroblast proliferation, the real pathologic process in rheumatic diseases--ASMC and fibroblast, both being mesenchymal cells--recommends the use of these drugs in the prevention and therapy of human arteriosclerosis. The surprising result of our in-vivo experiments, that the acceleration of the growth of the ASMC induced by risk factors and the inhibition of the growth induced by antirheumatic drugs persist in the subcultures, is explained by the "selection theory" that there are dissimilar kinds of ASMC in normal arteries and that they react differently.
Atherosclerosis 1979 Oct
PMID:Effect of risk factors and antirheumatic drugs on the proliferation of aortic wall cells. 22 70

Diabetes is associated with a fluctuating impairment in oxygen transport of the erythrocytes. This impairment is correlated with hyperglycemia by the formation of glycosylated hemoglobin (HbAIC) and with inhibitory factors of glycolysis i.e. hypophosphatemia and acidosis which lower the concentration of red cell 2,3-diphosphoglycerate. Diabetic angiopathy may be the ultimate result of innumerable microvascular responses to discrete hypoxic injuries associated with increased plasma permeation through the vessel walls. It is shown that two additional risk factors for atherosclerosis--smoking and hypertriglyceridemia may also lead to arterial wall hypoxia by changing the position of the oxyhemoglobin dissociation curve.
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PMID:Diabetic vascular disease. The importance of insulin deficiency, hyperglycemia and hypophosphatemia on red cell oxygen unloading. 27 65


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