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)

Normal and streptozotocin (STZ)-diabetic rats were studied in order to examine the effects of altering the type of dietary protein on cholesterol homeostasis. Rats were fed a non-purified or a purified diet containing either casein or soybean protein. The results obtained on the specific aspects of lipid metabolism were remarkably similar in control rats fed the non-purified (Purina Lab Chow) diet or the purified diet with the soybean protein. However, most of the findings obtained with the above two groups were different from those obtained with rats fed the purified diet containing casein. In the latter group, plasma cholesterol was elevated following a 15-day feeding period as compared to the other two dietary groups. The excess plasma cholesterol in the casein-fed group was found in two lipoprotein fractions with densities of 1.023-1.045 g/ml and 1.045-1.086 g/ml, respectively. The latter lipoprotein fraction was also enriched with apolipoprotein E. The casein-fed animals also showed a lower fractional rate of plasma cholesterol esterification and an abnormal accumulation of cholesterol in the body despite inhibition of cholesterol synthesis in the liver and in the intestines. Twelve to 15 days after the induction of diabetes, plasma cholesterol increased to a similar extent in the rats on all three diets. However, the distribution of cholesterol among the lipoprotein fractions was markedly different. The percentage of cholesterol in fractions of d less than 1.086 g/ml was increased while that carried in the fraction of d 1.086-1.161 g/ml decreased in the rats fed the nonpurified diet and the casein diet. In contrast, there was no change in the distribution of lipoprotein cholesterol between the diabetic and the control rats fed the soybean protein diet. The hepatic synthesis of cholesterol was unaltered in diabetic rats fed the nonpurified diet and the purified diet with soybean protein, but was increased 2.4-fold in diabetic rats fed casein. Intestinal cholesterol synthesis was increased in all three dietary groups. The increase was highest in the rats fed casein and lowest in rats fed soybean protein. The rate of sterol synthesis in the kidneys was not significantly affected by the diet or diabetes. In all three dietary groups diabetes led to an abnormal accumulation of cholesterol in the body. This accumulation was highest in the casein-fed rats and lowest in those fed the soybean protein diet. The cholesterol content of the kidneys was markedly increased by dietary casein.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary protein on cholesterol homeostasis in diabetic rats. 323 14

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type IIb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type IIb group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.
Diabetes 1987 Nov
PMID:Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia. 366 20

The effects of diabetes on plasma lipoproteins were examined in a cohort of control and streptozocin-alloxan diabetic beagles fed either standard rations or an atherogenic cholesterol-supplemented diet. Lipoprotein cholesterol, triglyceride, and retinyl ester concentrations were measured in fractions separated by density gradient ultracentrifugation. Individual lipoprotein classes and apolipoproteins were assessed by electrophoresis. Postheparin plasma lipoprotein triglyceride lipase activities were also examined. In the absence of added dietary cholesterol, diabetic animals became hypercholesterolemic with relatively increased low-density (LDL) and decreased high-density (HDL) lipoprotein cholesterol concentrations. Apolipoprotein E-containing beta- to alpha 2-migrating HDL1 (HDLc) appeared in rho = 1.020-1.080 g/ml subfractions, whereas alpha 1-migrating typical HDL (rho = 1.06-1.21 g/ml) was reduced. In comparison to nondiabetic cholesterol-fed animals, diabetic cholesterol-fed animals had increased cholesterol (but not triglyceride) concentrations in very-low- and intermediate-density classes. These classes contained retinyl esters and low-molecular-weight apolipoprotein B (components of intestinal lipoprotein remnants) as well as apolipoprotein E and high-molecular-weight apolipoprotein B. These findings could not be explained by decreased postheparin plasma lipoprotein lipolytic activities. Increased plasma concentrations of HDLc in poorly controlled diabetic dogs may reflect a pathologic disturbance in the excretory limb of cholesterol transport from peripheral cells to the liver. In addition, exaggerated retention of lipoprotein remnants in cholesterol-fed diabetic dogs may contribute to increased delivery of cholesterol to extrahepatic tissues. This model appears to be suitable for physiologic studies of the effects of diabetes on reverse cholesterol transport.
Diabetes 1986 Aug
PMID:Apolipoprotein E-containing lipoproteins and lipoprotein remnants in experimental canine diabetes. 373 34

The relationship between apolipoprotein E (apoE) polymorphism and plasma lipids and hyperlipemia was investigated in 105 male type II diabetics and 111 male nondiabetics. ApoE phenotypes were determined by a one-dimensional rapid flat gel isoelectric focusing method as described previously. The apoE phenotype frequency in diabetics was similar to that in nondiabetics. The frequency of hyperlipemia was higher in diabetics (56.2%) than in nondiabetics (32.4%). It was highest in the apoE3/2 group of diabetics and nondiabetics, followed by the apoE4/3 and apoE3/3 groups in the order described, indicating that the susceptibility to hyperlipemia differs among the apoE phenotype groups. ApoE3/2 diabetics had significantly higher levels of apoE and very-low-density lipoprotein (VLDL) cholesterol (chol)/VLDL triglyceride (TG) ratios than apoE3/3 diabetics. The effects of diabetes mellitus on plasma lipid levels differed among the various apoE phenotype groups: i.e., plasma total chol and low-density lipoprotein (LDL) chol increased only in apoE3/2 and apoE4/3 diabetics and plasma high-density lipoprotein chol decreased only in apoE3/3 diabetics, as compared with the corresponding apoE phenotype groups of nondiabetics, whereas plasma TG, VLDL TG, and VLDL chol increased in the three apoE phenotype diabetics. Furthermore, an increase of apoEII:apoEIII ratio was observed in apoE3/3 diabetics, particularly in those with hypertriglyceridemia. This study has also shown that the increased apoEII:apoEIII ratio is due to increased sialation of apoE based on the study of sialidase digestion of apo VLDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1986 Dec
PMID:Apolipoprotein E polymorphism and hyperlipemia in type II diabetics. 377 Mar 14

Noninsulin-dependent diabetics, whose plasma contained no detectable beta-VLDL (very low density lipoprotein), had a proportion (0.23 +/- 0.04) of plasma apolipoprotein E in the form of an abnormal lipoprotein not recognized by antibodies to apoB-100 from LDL (low density lipoprotein) or apoA-I from HDL (high density lipoprotein). This lipoprotein, abnormally rich in free cholesterol and apoE, had a calculated particle density within the low density lipoprotein range. It competed with LDL at the apoB,E receptor of normal fibroblasts and stimulated cholesteryl ester accumulation in mouse peritoneal macrophages. However, it did not compete with the binding of labeled rabbit beta-VLDL to macrophages. A much lower proportion of apoE (0.04 +/- 0.03) was in this form in the plasma of patients with insulin-dependent diabetes who had a comparable degree of hyperglycemia. The diabetic lipoprotein was absent in normoglycemic control subjects. The net transport of cholesterol from cell membranes to the plasma of noninsulin-dependent diabetics (and to a lesser extent, insulin-dependent diabetics) was inhibited relative to control values, and the magnitude of this inhibition was well correlated with the concentration of the abnormal lipoprotein of diabetes in plasma (r = 0.66 and 0.75, respectively). These findings suggest that diabetic plasma contains an abnormal and novel low density lipoprotein that mediates the abnormal cholesterol transport characteristic of human diabetes mellitus.
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PMID:Distribution of apolipoprotein E in the plasma of insulin-dependent and noninsulin-dependent diabetics and its relation to cholesterol net transport. 379 49

Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.
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PMID:Composition, removal and metabolic fate of chylomicrons derived from diabetic rats. 399 73

Amounts of plasma lipids, apolipoprotein AI (apo AI) and apolipoprotein E (apo E) were measured in streptozotocin-induced diabetic rats. Plasma triglyceride and cholesterol levels of diabetic rats were not significantly different from those of control rats. Plasma apo AI levels of diabetic rats were significantly higher than those of control rats (78.2 +/- 29.3 vs 27.2 +/- 3.4 mg/dl, P less than 0.001), while plasma apo E levels of diabetic rats were significantly lower than those of control rats (4.2 +/- 1.0 vs 13.9 +/- 5.3 mg/dl, P less than 0.001). Insulin treatment (12U/day) of diabetic rats decreased plasma apo AI levels significantly (treated: 32.8 +/- 3.4, untreated: 48.7 +/- 6.2, control: 28.5 +/- 2.4 mg/dl) and normalized plasma apo E levels (treated: 16.1 +/- 1.7, untreated: 5.4 +/- 0.7, control: 15.8 +/- 1.3). Insulin injection (4U/day) to normal rats did not cause any changes in both plasma apo AI and apo E levels. The data indicate that diabetes is not always accompanied by hyperlipidemia, however this inevitably carries apoprotein abnormalities characterized by the high plasma apo AI and low apo E levels, which are reversible with insulin treatment. The changes in the levels of plasma apo AI and apo E could be related to the development of atherosclerosis in diabetes.
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PMID:Reciprocal changes of plasma apo AI and apo E levels in streptozotocin-induced diabetic rats. 644 8

The disappearance rate of triacyl[3H]glycerol carried on very-low-density lipoproteins (VLDL), isolated from diabetic rats and reinjected into normal recipient rats, was about twice as low as that of VLDL-triacyl[3H]glycerol from non-diabetic rats. The VLDL derived from diabetic rats was deficient in the apolipoprotein E component. These results indicate that the triacylglycerol removal defect in diabetes may be related to the quality of the protein carrier.
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PMID:Removal defect of very-low-density lipoproteins from diabetic rats. 670 9

Plasma cholesterol metabolism in patients with poorly controlled noninsulin-dependent diabetes was characterized by inhibition of cholesterol net transport between cultured cells (fibroblasts) and plasma, inhibition of cholesterol esterification, and inhibition of cholesteryl ester transfer to low and very low density lipoproteins, relative to a normal control group. Plasma from these patients also contained a 2-fold higher level of apolipoprotein E (apo E). Effective control of hyperglycemia with insulin normalized both the parameters of plasma cholesterol metabolism and plasma levels of apo E. Removal of apo E by immunoaffinity chromatography normalized cell-to-plasma cholesterol transport but was without effect on the rate of cholesterol esterification or of cholesteryl ester transfer. These findings suggest that an inhibition in the chain of reactions by which cellular cholesterol is transferred in esterified form to low and very low density lipoproteins is associated with the appearance of an apo E-dependent "shunt" pathway, returning cholesterol from plasma back to the cells and so nullifying the normal cell-to-plasma transport pathway.
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PMID:Human noninsulin-dependent diabetes: identification of a defect in plasma cholesterol transport normalized in vivo by insulin and in vitro by selective immunoadsorption of apolipoprotein E. 695 24

To determine the role of apolipoprotein E (apoE) in diabetic hyperlipidemia, we induced diabetes in transgenic mice overexpressing apoE by intravenous injection of streptozotocin (STZ) and examined plasma lipoprotein metabolism in these mice. In STZ-induced diabetic mice, blood glucose levels were > 19 mmol/l (350 mg/dl) and plasma insulin levels were reduced to < 5 pmol/l (1 microU/ml). The diabetic nontransgenic mice developed hypercholesterolemia (plasma total cholesterol level: 4.55 +/- 1.32 vs. 1.97 +/- 0.13 mmol/l [176 +/- 51 vs. 76 +/- 5 mg/dl]) and hypertriglyceridemia (plasma triglyceride level: 0.82 +/- 0.29 vx. 0.42 +/- 0.11 mmol/l [73 +/- 26 vs. 37 +/- 10 mg/dl]) compared with values before induction of diabetes. In the diabetic nontransgenic mice, enhanced intestinal acylCoA:cholesterol acyltransferase activity was demonstrated, a factor that may contribute to the development of diabetic hyperlipidemia. Induction of apoE remarkably reduced the development of hyperlipidemia in diabetic transgenic mice compared with diabetic nontransgenic mice (plasma cholesterol level: 4.55 +/- 1.32 vs. 3.31 +/- 0.47 mmol/l [176 +/- 51 vs. 128 +/- 18 mg/dl], P < 0.01, and plasma triglyceride level: 0.82 +/- 0.29 vs. 0.17 +/- 0.11 mmol/l [73 +/- 26 vs. 15 +/- 10 mg/dl], P < 0.01). Plasma lipoprotein analysis by gel filtration chromatography showed that the reduction of plasma cholesterol and triglyceride levels was due to the disappearance of lipoproteins containing apoB. In these studies, we demonstrated the usefulness of STZ-induced diabetes in mice as an animal model for diabetic hyperlipidemia and demonstrated that endogenous induction of apoE in transgenic mice improved diabetic hyperlipidemia.
Diabetes 1995 May
PMID:Overexpression of apolipoprotein E prevents development of diabetic hyperlipidemia in transgenic mice. 772 19


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