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)

Significantly higher levels of erythrocyte membrane microviscosity (MV) [n-: 5.22 +/- 0.17 (4.70--5.92), mean +/- SD (range), poise, N = 67, P less than 0.005] measured by fluorescence depolarization using 1,6-diphenyl-1,3,5-hexatriene as a fluorescent probe were found in diabetic patients when compared with normal controls [5.05 +/- 0.15 (4.70--5.29), N = 22]. No significant differences in MV existed between males and females, nor was MV significantly correlated with diabetic age, duration of diabetes, plasma cholesterol, cholesterol/phsopholipid ratios, and plasma lecithin:cholesterol acyltransferase activities. No significant difference in MV was observed between groups with or without diabetic retinopathy. There was, however, significantly higher MV [5.29 +/- 0.19 (5.00--5.92), N = 20, P less than 0.05] in the group with fasting blood glucose (FBG) greater than or equal to 140 mg/dl than that [5.19 +/- 0.15 (4.70--5.46), N = 47] in the group with FBG less than 140 mg/dl. The changes in erythrocyte membrane MV presented in this study appear to be related to the current metabolic control of diabetic patients and are considered to be one of the factors responsible for the reduced erythrocyte deformability in diabetes.
Diabetes 1979 Dec
PMID:Higher levels of erythrocyte membrane microviscosity in diabetes. 51 Aug 12

Basal values of lecithin:cholesterol acyltransferase (LCAT) were estimated in healthy subjects, in patients with the so-called risk ischemic heart diseases (IHD)--obesity, diabetes, hypertension, and hyperlipoproteinemia II--and in patients with a IHD-infarction of the myocardium. A precise method employing a 14C-4-cholesterol-labeled common normolipidemic substrate was used. A highly significant difference in the average values of LCAT activity between healthy men and women was found. LCAT in men with 'risk' diseases decreased, while in women it remained at the level of the reference group. To assess the dependence between LCAT-dependent indicators and IHD, criteria for evaluating the deviations from reference values were proposed. The number of deviations from the reference group increased in the sequence: obesity, hypertension, diabetes, hyperlipoproteinemia, and the infarction of the myocardium.
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PMID:Lecithin:cholesterol acyltransferase as a possible diagnostic tool in ischemic heart disease. 74 40

The effects of four months' physical exercise on serum lipids, lipoproteins and lipid metabolizing enzymes were studied in 25 non-insulin-dependent diabetic patients divided randomly into exercise (n = 13) and control (n = 12) groups. Exercise induced a significant decrease in serum LDL-cholesterol and an increase in serum HDL-cholesterol and HDL2-cholesterol. Triglycerides showed a temporary decrease. Apoproteins A1 and B were virtually unchanged. Postheparin plasma lipoprotein lipase increased markedly during the exercise period while no change occurred in adipose tissue lipoprotein lipase, hepatic lipase or lecithin:cholesterol acyltransferase. In the control group no significant changes occurred in any of the lipid variables. In the light of the knowledge of LDL-cholesterol as a causative and HDL-cholesterol as a protective factor in atherogenesis in non-diabetics the changes caused by exercise in non-insulin-dependent diabetics can be considered favourable.
Diabetes Res 1988 Feb
PMID:Effects of long-term physical exercise on serum lipids, lipoproteins and lipid metabolizing enzymes in type 2 (non-insulin-dependent) diabetic patients. 339 67

We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandial triglyceride (TG)-rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:cholesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intestinal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a preponderance of small dense LDL particles present in the plasma and reduced amounts of large buoyant species when compared to normotriglyceridaemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concentrations of proinsulin (P < 0.05), although insulin content did not differ significantly. 32-33 split proinsulin (SPI) was the major insulin-like molecule present in HTG and was present in significantly higher amounts in these patients (P < 0.05) than either NTG or control subjects and correlated significantly with the presence of small dense LDL particles. After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylomicron remnants were present to a greater extent in HTG than in NTG and controls (P < 0.05), although in this case NTG also contained more chylomicron remnants than control subjects (P < 0.05). There was no difference in the LPL activity, CETP and LCAT between diabetics and controls, whereas an increase in hepatic lipase activity was seen in the HTG diabetics (P < 0.05). Both CETP and LCAT activities increased postprandially. Multivariate analysis showed that TG, HDL content and HL activity were the most important determinants of small dense LDL concentration in the fasting state (R2 = 67%). Postprandially, chylomicron remnant clearance, HL and insulin resistance were the major determinants (R2 = 61%) of LDL-III.
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PMID:Fasting and postprandial determinants for the occurrence of small dense LDL species in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia: the involvement of insulin, insulin precursor species and insulin resistance. 760 66

Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome or chronic renal disease and also in those undergoing haemodialysis and with renal transplant. Even though the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man is unclear, experimental and clinical data indicate a possible damaging effect of a disturbed lipid metabolism on the kidney. In humans, glomerular lipid deposition is observed in genetic diseases such as Fabry's disease, lecithin:cholesterol acyltransferase activity (LCAT) deficiency and arteriohepatic dysplasia, and in diseases with acquired disturbance of lipid metabolism such as nephrotic syndrome and cholestatic liver disease. Studies on animals with lupus nephritis, aminonucleoside nephrosis, reduced renal mass, diabetes mellitus or systemic hypertension have shown that cholesterol can increase the incidence of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile to that of man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have given some preliminary insights into the cellular mechanisms of lipid induced glomerular damage. Apo E-containing lipoproteins, which are pathologically elevated in many renal diseases, are avidly taken up by human mesangial cells. These cells seem to play a central role in the initiation of glomerulosclerosis by inducing proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells, and increase the synthesis of mitogens and extracellular matrix protein. The pathogenic role of oxidized lipoproteins has not yet been defined. Human mesangial cells do not seem to take up these modified lipoproteins. However, macrophages infiltrate glomeruli and may constitute the stimulus for the generation of minimally modified lipoproteins and their cellular uptake. The data from animal experiments suggest that treatment that corrects hyperlipidemia may have an ameliorative effect on renal function. Thus, there are strong indications that lipoproteins may play a critical role in mediating the development of glomerulosclerosis.
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PMID:The role of lipids in nephrosclerosis and glomerulosclerosis. 794 52

On initial diagnosis or when metabolic control is poor, subjects with type 1 (insulin-dependent) diabetes mellitus often exhibit decreased high density lipoprotein (HDL) cholesterol levels, which have been associated in numerous studies in non-diabetic subjects with atherosclerosis and coronary artery disease. We measured the activities of plasma lecithin:cholesterol acyltransferase (LCAT), post-heparin lipoprotein lipase, and the composition of the HDL subfractions HDL2 and HDL3, in ten poorly controlled type 1 diabetic patients admitted to a metabolic ward (six women and four men, aged 18-37 years). The measurements were repeated after metabolic control had been optimised and again a week after discharge. The results were compared with those of ten healthy normolipidaemic subjects matched for age, sex and body mass. LCAT activity increased significantly (P < 0.05) with improved metabolic control in the diabetic patients, and showed positive within-person correlation with HDL2 cholesterol ester (r = 0.67; P < 0.01), HDL2 free cholesterol (r = 0.67; P < 0.01), phosphatidylcholine (r = 0.49; P < 0.05), total phospholipids (r = 0.50; P < 0.01) and apolipoprotein A-I (apo A-I: r = 0.72; P < 0.01). With improving metabolic control HDL2 lipid levels increased more than twofold and the compositional changes in HDL2 were reflected by an increased apo A-I:apo A-II ratio (P < 0.05) and a decreased triglyceride:apo A-I ratio (P < 0.05). Changes in HDL3 levels and composition were minor. The results of this study indicate that an increase in LCAT activity increases the concentration and changes the composition of HDL2 in type 1 diabetic patients with improved metabolic control.
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PMID:Lecithin:cholesterol acyltransferase activity and high-density lipoprotein subfraction composition in type 1 diabetic patients with improving metabolic control. 811 Oct 77

Chronic renal failure (CRF) in nondiabetics is associated with a number of lipoprotein abnormalities that place these patients at high risk for atherosclerosis. This study compared the lipoprotein composition of nondiabetic controls (n = 68) with that of patients with insulin-dependent diabetes mellitus ([IDDM] n = 13) and of patients with IDDM and CRF ([IDDM + CRF] n = 74). Six lipoprotein subfractions (very-low-density lipoprotein [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], high-density lipoprotein-light [HDL-L], HDL-medium [HDL-M], and HDL-dense [HDL-D]) were isolated by rapid gradient ultracentrifugation using a fixed-angle rotor. The apolipoprotein (by reverse-phase high-performance liquid chromatography [HPLC]) and lipid (by enzymatic assays) composition of each subfraction was determined. The only abnormalities found in IDDM patients were increases in IDL and HDL-L triglyceride (TG) levels and an increase in the HDL-L free cholesterol (FC) level. The IDDM + CRF group had multiple abnormalities including (1) elevated TG, apolipoprotein (apo) C-II, and apo C-III levels in all lipid subfractions; (2) elevated VLDL and IDL apo B, TG, FC, cholesterol ester (CE), and phospholipid (PL) levels (with an increased CE/TG ratio in VLDL only); (3) decreased HDL-M apo A-I, apo A-II, CE, and PL levels, but an increased HDL-D apo A-I level; and (4) decreased lecithin:cholesterol acyltransferase (LCAT) activity. Twenty-five of the IDDM + CRF patients underwent combined pancreas and kidney (P + K) transplantation, and 12 patients received only a kidney transplant. Lipoprotein composition was determined at 3, 6, and 12 months posttransplant. Both types of transplantation resulted in similar alterations in lipoprotein composition, even though there was essential normalization of blood glucose levels in most of the patients who received a pancreas transplant (hemoglobin A1C [HbA1C], 9.1% +/- 1.1% v 5.7% +/- 0.3% at 12 months, P < .01). These posttransplant changes included (1) no improvement in the elevated TG level in any lipid subfraction even though there was some reduction in apo C-III levels in VLDL; (2) reductions in levels of VLDL and IDL apo B but increases in LDL apo B; (3) increases in HDL apo C-III and FC concentrations despite an increase in LCAT activity; and (4) increases in apo A-I levels in HDL-L and HDL-M. The addition of a pancreas to a kidney transplant had no obvious impact on the lipoproteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Lipoprotein composition in insulin-dependent diabetes mellitus with chronic renal failure: effect of kidney and pancreas transplantation. 813 82

Arterial hypertension is a dominant pathogenetic factor for glomerulosclerosis. Nevertheless metabolic factors such as hyper- or dyslipoproteinemia may significantly modify and accelerate the process of glomerular scarring. Hyperlipidemia and lipoprotein abnormalities are often encountered in patients with nephrotic syndrome and chronic renal disease. Although the significance of lipid deposition in renal tissue and the role of lipoproteins in the pathogenesis of renal disease in man has not yet been clearly defined, experimental and clinical data indicate a damaging effect of disturbed lipid metabolism on the kidney. In humans glomerular lipid deposition is observed in several genetic diseases, including lecithin-cholesterol acyltransferase activity deficiency. Studies on animals with reduced renal mass, diabetes mellitus or arterial hypertension have shown that hypercholesterolemia increases the incidence of glomerulosclerosis. Especially the interaction of arterial hypertension and dyslipoproteinemia leads to a rapid and pronounced development of glomerulosclerosis. As most of these studies have been performed in the rat, which has a different lipoprotein profile than man, these results should be carefully interpreted with regard to their relevance for humans. In vitro cell culture studies on human glomerular cells have provided insight into the possible cellular mechanisms of lipid-induced glomerular damage. Apoprotein E containing lipoproteins that are pathologically elevated in many renal diseases are avidly taken up by human glomerular cells. Mesangial cells seem to play a central role in the initiation of glomerulosclerosis by proliferation and production of excess extracellular matrix. Lipoproteins are able to stimulate DNA synthesis in these cells and increase the synthesis of mitogens and matrix proteins. The pathogenetic role of modified, oxidized lipoproteins has not yet been elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arterial hypertension and hyperlipidemia as determinants of glomerulosclerosis. 830 44

Non-enzymatic glycation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Glycated apolipoprotein A-I isolated from diabetic subjects was tested in vitro for its ability to activate lecithin:cholesterol acyltransferase, the principal cholesterol-esterifying enzyme in plasma. Activation by glycated apolipoprotein A-I was significantly lower at all concentrations than the activation by normal apolipoprotein A-I. Linear regression analysis of the kinetic data shows that the ratio app Vmax/app Km was significantly lower (p < 0.01) for glycated apolipoprotein A-I (0.29 nmol.l/h.mumol) than for normal apolipoprotein A-I (0.78 nmol.l/h.mumol). Because lecithin:cholesterol acyltransferase provides a driving force in reverse cholesterol transport by esterifying the cellular cholesterol removed by HDL, it is tempting to postulate that this abnormal activation may be associated with a reduction in reverse cholesterol transport and associated with the accelerated development of atherosclerosis in diabetic patients.
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PMID:Decreased activation of lecithin:cholesterol acyltransferase by glycated apolipoprotein A-I. 831 68

We report a new genetic defect in the lecithin:cholesterol acyltransferase (LCAT) gene associated with classical clinical and biochemical features of fish eye disease. The 63-year-old Australian female proband also suffers from non-insulin-dependent (type II) diabetes mellitus. She presented with corneal opacities, markedly reduced HDL-cholesterol (0.1 mmol/L; < 10% of normal controls), and elevated plasma triglycerides. The presence of diabetes did not explain the lipoprotein profile, which differed markedly in comparison to two female hypertriglyceridemic diabetic subjects. Cholesterol esterification in HDL-like particles was minimal but plasma cholesterol esterification was maintained due to LCAT activity in non-HDL-containing lipoprotein fractions. DNA sequence analysis of the proband's LCAT gene showed two C to T transitions resulting in the substitution of Thr123 with Ile and Tyr144 with Cys. Allele-specific PCR amplification procedures were used to confirm the presence of the mutations in this proband and to screen for additional carriers in her family. Three first degree relatives (mother, brother, son) were heterozygous for the Thr123 --> Ile mutation and her daughter had the Tyr144 --> Cys mutation. Apart from a reduction in HDL-cholesterol levels to half the normal concentration and a 20% reduction in apoA-I levels, their plasma lipids were unremarkable. The proband's son and daughter were further investigated. Both had normal cholesterol esterification rates in plasma and VLDL/LDL-depleted plasma, but reduced LCAT activity (50% that of normal). Thus, the biochemical and phenotypic expression for fish eye disease in the heterozygote subjects was similar, irrespective of the underlying LCAT mutation.
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PMID:A new molecular defect in the lecithin: cholesterol acyltransferase (LCAT) gene associated with fish eye disease. 882 Jan


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