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)

High carbohydrate (CHO) diets cause accumulation in plasma of larger, triglyceride (TG)-enriched very low density lipoprotein (VLDL) particles. In man, the composition of the VLDL is changed by such diets as well. The source of the altered VLDL particles is presumed to be the liver, but the intestine is known to secrete VLDL, and VLDL is also altered during its postsecretory catabolism. To ascertain that the liver is a source of "diet-induced VLDL," we fed rats CHO and control diets and we examined plasma levels of lipids chemically and apoproteins A-I (ApoA-I) and B (ApoB) by specific radioimmunoassay (RIA). VLDL (d less than 1.006) and VLDL density subfractions were isolated and their composition studied by RIA, column chromatography, isoelectric focusing (IEF), and polyacrylamide gel electrophoresis. Livers from control and CHO-fed rats were perfused in vitro. Whole perfusates and perfusate VLDL were studied similary. In the CHO-fed rats, plasma TG increased, cholesterol and ApoA-I remained unchanged, and ApoB fell. The VLDL isolated were TG enriched and less dense. Although total VLDL-protein rose, the proportion of VLDL-protein that was ApoB and arginine-rich protein (ARP) fell, while ApoC rose. The ApoB content varied directly with density of particles. ARP subunits were not changed, but relative proportions of ApoC-III0 rose from 39 to 46 per cent of dye uptake on IEF gels and ApoC-III3 fell from 34 to 26 per cent. Thus, CHO feeding produced altered plasma VLDL in the rat. The perfused livers of the CHO-fed rat secreted more TG, but absolute secretory rates for cholesterol, ApoB, and ApoA-I were unchanged. The VLDL isolated from perfusates were larger, TG-enriched, and less dense. Although VLDL-protein rose, the proportion that was ApoB fell; both ApoC and ARP rose, ARP subunits were unchanged, while ApoC-III0 rose from 29 to 37 per cent and ApoC-III3 fell from 48 to 42 per cent. In contrast to plasma, ApoC content was not increased relative to ARP. As in plasma, content of ApoB varied with particle density. Thus, CHO feeding induced changes in hepatic perfusate VLDL structure and composition that in general paralleled those changes seen in plasma. This strongly suggests that the action of diet on the liver is responsible for many of the changes seen in plasma VLDL. On the other hand, the discrepancy between the VLDL-ApoC content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing. Similarly, the failure to see decreases in absolute hepatic ApoB secretion, while plasma ApoB levels fell, suggests that the postsecretory metabolism of ApoB-containing lipoproteins is also altered by diet. In addition, the failure to see increases in hepatic VLDL-ApoB secretory rates at a time when VLDL-TG and VLDL-protein increased suggests that there is no tight coupling between the secretion of ApoB and lipids.
Diabetes 1978 Dec
PMID:Carbohydrate diet-induced changes in very low density lipoprotein composition and structure. 21 69

The levels of lipoprotein A-I (LP A-I) containing apolipoprotein A-I (apo A-I) and devoid of apolipoprotein A-II (apo A-II) have been determined in a group of 86 children and adolescents with insulin-dependent diabetes of age between 1.3 and 22 years. The duration of diabetes in the studied group ranged between 0.25 and 15 years. The patients studied were further divided into subgroups taking into account the duration of diabetes as well as the occurrence of complications of diabetes, obesity and predisposition to early development of atherosclerosis in family history. The analysis of the results took into account the relations between the levels of LP A-I and other parameters of lipid metabolism like cholesterol, triglycerides, HDL-cholesterol, apo A-I and apo A-II concentrations as well as the effectiveness of metabolic control of diabetes. LP A-I concentration was the lowest in group of children with diabetes lasting up to one year. This parameter was correlated positively with the levels of HDL-cholesterol and apo A-I, and negatively with HbA1c. It was not related to the coexisting complications, obesity or predisposition to atherosclerosis in family history. The above results indicate that the state of metabolic control of diabetes significantly influences the level of LP A-I. Considering the importance of LP A-I in preventing atherosclerosis it should be stressed that a decrease in its level during the period of prolonged hypoglycemia constitutes still another risk factor for development of atherosclerosis in diabetic children and adolescents.
 ...
PMID:[Lipid metabolism in children and adolescents with insulin dependent diabetes. II. Evaluation of changes in lipoprotein A-I in children and adolescents with insulin dependent diabetes]. 134 32

The purpose of this study was to examine the change in apolipoprotein and lipoprotein levels in patients with normolipidemic untreated non-insulin-dependent diabetes mellitus (NIDDM). Fifteen untreated, non-obese male NIDDM patients without hyperlipidemia were chosen, and 15 healthy subjects, matched for age, sex, body weight, alcohol consumption and cigarette smoking served as the control group. We observed that the concentrations of plasma total cholesterol (TC), triacylglycerol (TG) and very low density lipoprotein cholesterol (VLDL-C) were identical in both NIDDM and control groups. The levels of low-density lipoprotein cholesterol (LDL-C) were slightly increased in the diabetic group, but the difference did not reach statistical significance in our study. High-density lipoprotein cholesterol (HDL-C) was lower in the NIDDM group than in the controls. Significantly increased TC/HDL-C and LDL-C/HDL-C ratios were found in NIDDM patients compared with controls. The apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) levels were decreased in NIDDM patients, while the apolipoprotein B (apo B) level remained similar to that of the control subjects. The ratio of apo A-I/apo B was decreased significantly in the NIDDM group. Our results suggest that NIDDM patients are at higher risk of coronary heart disease, even if they remain normolipidemic.
 ...
PMID:Apolipoprotein levels in normolipidemic non-insulin-dependent diabetes mellitus. 135 44

Primary familial forms of chylomicronemia can lead to acute life-threatening complications, especially acute pancreatitis. The main aim of therapy is to avoid this so-called chylomicronemia syndrome. In 12 patients with primary chylomicronemia due to familial hypertriglyceridemia, the addition of 2.16 g omega-3 fatty acids over 4 weeks and 4.32 g for 8 weeks resulted in a decrease of serum triglyceride levels from 1,624 +/- 333 to 894 +/- 241 mg/dL after 12 weeks. Cholesterol and triglyceride levels in the chylomicron fraction were reduced concomitantly, the apolipoprotein B-100/B-48 ratio increased, very--low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol, and total cholesterol levels decreased, and low-density lipoprotein (LDL) cholesterol showed a tendency to increase, but this finding did not reach significance. High-density lipoprotein (HDL) cholesterol levels remained unchanged, as did the levels of apolipoproteins A-I, A-II, and E, and lipoprotein(a). Apolipoprotein B levels decreased significantly. The decrease of triglyceride levels to still-elevated concentrations was accompanied by a substantial decrease in plasma and whole-blood viscosity and erythrocyte aggregation, which reached normal values. As in chylomicronemia, complications usually occur at triglyceride levels higher than 1,500 mg/dL; patients can still profit from treatment with omega-3 fatty acids, even though triglyceride levels are still substantially elevated. No clinically relevant side effects occurred, with the exception of the manifestation of diabetes mellitus in one patient, which could be reversed after discontinuation of treatment.
 ...
PMID:Treatment of primary chylomicronemia due to familial hypertriglyceridemia by omega-3 fatty acids. 140 95

Patients on maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) exhibit numerous disturbances of serum lipids and apoproteins that may contribute to their high cardiovascular mortality. Cross-sectional studies have found that lipid levels are inversely related to time on dialysis. However, it is not known whether this association is the result of the attrition of hyperlipidemic patients or a decrease in lipid levels over time in all patients. Additionally, few studies have investigated the effect of dialysis modality on the lipoprotein disturbances of uremia adjusting for the confounding influences of demographics, or nutritional and endocrine status. To address these issues, we undertook a cross-sectional and longitudinal study of lipids, apoproteins, and atherogenic risk ratios in patients maintained on HD and CAPD. Patients were enrolled in annual cohorts from 1987 to 1990 and monitored until 1991. A total of 196 HD and 77 CAPD patients were studied. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I, and apo B were measured on enrollment and remeasured annually in survivors through 1990. Using multivariate methods, we examined the relationship of the lipids, apoproteins, their respective ratios, and their changes over time, to a broad range of clinical factors and to mortality. Compared with HD patients, CAPD patients had significantly higher TC, apo A-I, and apo B, and a significantly lower apo A-I/apo B ratio. Serum albumin correlated directly with TC and apo B and inversely with apo A-I/apo B. For patients with normal serum albumin (> or = 3.5 g/dL [35 g/L]), CAPD patients had a significantly higher TC/HDL-C than HD patients; otherwise the ratios were similar for CAPD and HD. Independent influences on lipoprotein levels in HD and CAPD patients were also demonstrated for race, gender, and diabetes, but not for parathyroid hormone (PTH) levels. For both dialysis modalities, patients who died had significantly lower TC and apo B, and significantly higher apo A-I/apo B throughout their entire courses compared with survivors. In the subset of patients followed longitudinally for 2 or more years, apo B tended to decrease with time, but TC, HDL-C, and apo A-I were stable. The longitudinal changes in lipoproteins did not correlate with outcome or other factors. In conclusion, CAPD patients have more atherogenic lipoprotein profiles than HD patients. Improved visceral protein nutritional status, as defined by serum albumin level, is associated with hyperlipidemia and, especially vor CAPD, worsened atherogenic risk ratios.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The uremic dyslipidemia: a cross-sectional and longitudinal study. 141 99

To investigate the possible relevance of free radicals and prostanoids to the mode of initiation and/or evolution of microangiopathy in diabetes mellitus, we measured serum lipid peroxides (LPO), an accepted index of intravascular free radicals, and plasma 11-dehydrothromboxane B2 (11-dehydro-TXB2), a stable metabolite of vasoactive thromboxane A2 released from platelets, in 95 patients with normolipidemic type 2 (non-insulin-dependent) diabetes mellitus at different stages of the disease. In general, either LPO or 11-dehydro-TXB2 was significantly greater in the patients, as a group, than in the matched controls (3.82 vs. 2.65 nmol/ml, P < 0.01 for LPO; and 17.3 vs. 5.8 pg/ml, P < 0.01 for 11-dehydro-TXB2). In patients, both LPO and 11-dehydro-TXB2 increased according to the severity of their diabetic retinopathy. A highly significant positive correlation existed between the LPO values and 11-dehydro-TXB2 in the patients (r = 0.64, P < 0.0001), while there was no such relationship in the controls (r = 0.18, P = NS). No difference in serum levels of apolipoproteins A-I, A-II, B, C-II, C-III, or E was observed between the patients and controls. Short-term glycemic control (25 cal/kg of standardized body weight/day, for 8 weeks) resulted in a small but significant reduction in LPO (4.2 vs. 4.6 nmol/ml, control; P < 0.05) without alteration in 11-dehydro-TXB2. There was a tendency towards deterioration in LPO according to the improvement in glycemic control. These results appear consistent with the view that, in addition to LPO, the release of TXA2 from activated platelet in the human circulation could be an important factor for the initiation and/or evolution of microangiopathy in diabetic patients even when they are not apparently hyperlipidemic. Further, the results of the present study emphasize the notion that more tight control of serum lipids is worthy of serious consideration in preventing the advance of diabetic microangiopathy.
Diabetes Res Clin Pract 1992 Nov
PMID:Possible relevance of lipid peroxidation and thromboxane production to the initiation and/or evolution of microangiopathy in non-hyperlipidemic type 2 diabetes mellitus. 147 57

The effect of L-arginine on the arginase activity and polyamine levels was studied in the pancreas of normal and diabetic rats (120 mg/kg alloxan, i.v.). Four groups were formed (10 male adults per group). I-Control-0.154 M NaCl. II-Diabetic-0.154 M NaCl (96 h after alloxan). III-Control plus 10 mM L-arginine IV-Diabetics plus 10 mM L-arginine. Rats were sacrificed 20 min after L-arginine injection. Glucose in serum and dry weight, proteins, arginase activity and polyamines (HPLC) in pancreas were measured. Higher ratio mg protein/mg dry weight and arginase induction was observed for groups III and IV. Putrescine was low as a consequence of diabetes but restored with L-arginine. The concentrations of spermidine and spermine were lower. These results may suggest that arginine is metabolized to putrescine in the pancreas and that polyamines may be utilized in regenerating processes or for recovering the endocrine pancreatic function.
 ...
PMID:Effect of L-arginine on pancreatic arginase activity and polyamines in alloxan treated rats. 148 95

Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/l) and in nondiabetic men (n = 18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p less than 0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.
 ...
PMID:Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus. 151 63

Lipoprotein particles containing apoA-I but not apoA-II are, among high-density lipoproteins, effective protectors against atherosclerosis that act by promoting the efflux of cellular cholesterol and the reverse cholesterol transport process. Because previous studies showed that in vitro nonenzymatic glycosylation of HDL impairs HDL receptor-mediated cholesterol efflux, we isolated Lp A-I from two poorly controlled insulin-dependent diabetic patients and compared the chemical composition and ability to promote cholesterol efflux with the same particles purified from two matched nondiabetic control subjects. No differences in lipid composition or in the ability to promote cholesterol efflux from cultured adipose cells were noted between the two types of Lp A-I preparations. However, when we separated Lp A-I from diabetic subjects by degree of glycosylation, the specifically glycosylated subfractions were about 50% less effective in producing cholesterol efflux than the nonglycosylated particles.
Diabetes 1992 Oct
PMID:Apolipoprotein A-I-containing particles and reverse cholesterol transport in IDDM. 152 42

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.
 ...
PMID:Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease. 153 90


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