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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contrary to normal rats, diabetic rats are known to develop marked hypercholesterolemia when fed a cholesterol-enriched diet. The triggering factor involved in this hyperresponse has not been identified. With the aim of clarifying the role of the intestinal acyl-CoA:cholesterol acyltransferase (ACAT), we studied the effects of a high fat diet and the changes of intestinal ACAT activity during the early development of streptozotocin-diabetes in rats. Feeding diabetic rats with a diet enriched in cholesterol and saturated fat produced an increase in plasma and in tissue cholesterol as early as 3 days after streptozotocin injection in the absence of hyperphagia. Under these experimental conditions, treatment with insulin or with the ACAT inhibitor CL-277082 significantly reduced the plasma cholesterol to levels measured in nondiabetic rats fed the same high fat diet. An increase in [14C]cholesterol in plasma very low density lipoprotein was observed after oral administration of labeled cholesterol to 3-day diabetic rats. In parallel experiments, the direct measurement of small intestine microsomal ACAT activity revealed an increase, averaging 288% in diabetic rats 3 days after diabetes induction. This change in ACAT activity occurred simultaneously with an increase in plasma glucagon and was normalized by insulin treatment. The induction of intestinal ACAT activity in diabetic rats, its modulation by insulin, and the hypocholesterolemic effects of insulin or CL-277082 treatment clearly indicate that ACAT activity plays a major role in the initiation of diabetes-associated hypercholesterolemia.
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PMID:Role of the intestinal acyl-CoA:cholesterol acyltransferase activity in the hyperresponse of diabetic rats to dietary cholesterol. 143 72

Lipids, apoproteins and associated enzyme activities in type 2 diabetic end-stage renal disease (ESRD) were compared with that in nondiabetic ESRD and normal controls. Of the 40 uremic patients with non-insulin-dependent diabetes mellitus, 20 patients were receiving stable continuous hemodialysis treatment (CHT). Of the 39 patients with nondiabetic ESRD, 21 were undergoing CHT. Patients with nondiabetic ESRD exhibited elevated levels of serum triglyceride and a marked reduction in high-density-lipoprotein (HDL) cholesterol. Concentrations of serum apolipoprotein (Apo) C-3 were higher than in controls, whereas mean levels of serum Apo E were lower. The concentrations of serum Apo A-1 and Apo A-2 decreased with diminished lecithin: cholesterol acyltransferase activity. Lipoprotein lipase activity decreased in undialysed patients, and hepatic triglyceride lipase activity decreased significantly throughout the observation. Patients with diabetic ESRD exhibited elevated serum Apo B and normal serum Apo E levels, besides the lipid and Apo abnormalities observed in nondiabetic ESRD. Moreover, a prominent reduction in serum Apo A-1 was found in dialysed diabetic patients. The Apo B/Apo A-1 ratio was significantly higher in diabetic ESRD than in nondiabetic patients undergoing CHT. These results indicate that lipid abnormalities are accelerated in diabetic ESRD and may constitute a serious risk for the development of atherosclerosis.
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PMID:Comparison of lipids, apoproteins and associated enzyme activities between diabetic and nondiabetic end-stage renal disease. 150 37

The purpose of this study was to characterize the lipoprotein profile and cholesterol metabolism in Yoshida rats, a strain of inbred genetically hyperlipemic animals. For comparison, Brown Norway rats were used as control animals. Plasma cholesterol and triglycerides were higher in Yoshida as compared to Brown Norway, the elevation of cholesterol being due to a rise in HDL fraction. Triglyceride distribution among lipoproteins showed an increase in VLDL fraction. Hyperlipemia was not related to diabetes, hypothyroidism or nephropathy. Plasma triglycerides production was increased in Yoshida rats, while lipoprotein and hepatic lipases were similar in the two groups. Hypercholesterolemia was associated with a defect of lipoprotein receptor activity and with elevated HMG-CoA reductase and cholesterol 7 alpha - hydroxylase; conversely ACAT activity was lower in Yoshida as compared to Brown Norway rats. Sterol fecal excretion was comparable in the two groups and hypercholesterolemia in Yoshida rats was not associated to an increase of cholesterol saturation of the bile. We suggest that lipoprotein overproduction is the main cause for hyperlipidemia in this strain of rats.
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PMID:Plasma lipoproteins and cholesterol metabolism in Yoshida rats: an animal model of spontaneous hyperlipemia. 159 76

We investigated plasma lipoprotein profiles and the activities of tissue cholesterol regulating enzymes in Wistar fatty rats, an animal model for non-insulin-dependent diabetes mellitus (NIDDM). Wistar fatty rats were made by transfer of the fa gene to the Wistar Kyoto rats by backcross-breeding. Wistar fatty and control non-diabetic littermates were given a laboratory chow or an atherogenic diet containing 1 percent (weight percent) cholesterol, 0.5 percent cholic acid, and 5 percent lard. Under the chow diet, plasma fasting glucose and immunoreactive insulin concentrations in Wistar fatty rats were 1.5- and 6-fold higher than controls, respectively. Plasma cholesterol was significantly increased in Wistar fatty rats compared with controls. Elevated plasma cholesterol levels in Wistar fatties was accounted for by the increases of cholesterol content in the d less than 1.006 g/ml lipoprotein and high-density lipoproteins. Under the atherogenic diet, plasma cholesterol levels in Wistar fatties were further increased by 129 percent compared with controls. The diet-induced increase of cholesterol contents was shown in all lipoprotein classes for Wistar fatty rats. The activities of regulatory enzymes for cholesterol biosynthesis or absorption were measured in Wistar fatty rats. Both hepatic and intestinal 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities were significantly higher in Wistar fatty rats than those in controls (P less than 0.05 and P less than 0.01, respectively). ACAT activities in Wistar fatties were significantly increased in the intestine (P less than 0.05) and decreased in the liver in comparison with controls (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormalities of plasma lipoproteins in a new genetically obese rat with non-insulin-dependent diabetes mellitus (Wistar fatty rat). 189 25

The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P less than 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P less than 0.01), hepatic HMG-CoA reductase (P less than 0.05) and ACAT (P less than 0.001), and phenol 2-monooxygenase (P less than 0.01). The poorly controlled animals were hypercholesterolemic (P less than 0.01), and this was reflected in the very-low-density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated.
Diabetes 1990 May
PMID:Cholesterol metabolism in alloxan-induced diabetic rabbits. 233 20

Diabetes mellitus is accompanied by increased intestinal cholesterol synthesis and cholesterol esterification. Both are reversed by insulin therapy. To assess whether the action of insulin on cholesterol esterification by intestinal cells is direct or mediated by other effectors associated with diabetes, we investigated the effect of insulin on the activity of microsomal acyl-CoA:cholesterol acyltransferase (ACAT) and on the incorporation rate of [14C]oleic acid into cholesteryl oleate in the Caco-2 human intestinal cell line. Microsomal ACAT activity of cells that were incubated with insulin for 3 h at a concentration of 1, 10, and 100 microU/ml was decreased by 48, 58, and 74%, respectively, compared with cells cultured in insulinfree medium. This effect was evident as soon as 10 min after the addition of 10 microU/ml insulin. The inhibition by insulin was reversible. After incubation for 24 h, intracellular esterified-cholesterol content and the ratio of esterified to nonesterified cholesterol were significantly lower in the cells treated with insulin (100 microU/ml) than in those not treated with insulin (esterified cholesterol 48.6 +/- 2.0 vs. 74.2 +/- 4.3 nmol/mg protein, respectively, P less than .005; esterified to nonesterified ratio 0.280 +/- 0.008 vs. 0.359 +/- 0.059, respectively, P less than .05). Cells cultured on filters manifested physiologic polarity; greater than 90% of [14C]oleic acid-labeled cholesterol ester secreted by cells was secreted into the basolateral chambers. Incorporation of [14C]oleic acid into cholesteryl oleate over 24 h in the cells and in the medium of the basolateral chamber was suppressed by 100 microU/ml insulin by 23 and 40%, respectively. These findings indicate that insulin acts directly on the enterocytes to suppress intestinal cholesterol ester synthesis and secretion.
Diabetes 1989 May
PMID:Decreased activity of acyl-CoA:cholesterol acyltransferase by insulin in human intestinal cell line Caco-2. 265 31

We examined the activities of intestinal acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol esterase, enzymes regulating cholesterol absorption, in rats with streptozocin-induced diabetes (STZ-D) to clarify the effect of diabetes on cholesterol absorption. Three weeks after the induction of diabetes, plasma cholesterol levels were slightly but significantly increased in diabetic rats compared with control animals, whereas a far more remarkable increase in plasma cholesterol was observed in diabetic rats when fed an atherogenic diet containing 1% cholesterol, 0.5% cholic acid, and 5% lard. Microsomal ACAT activity in intestinal mucosa was three times higher in diabetic than in control rats. However, no significant difference in the enzyme activity could be detected between diabetic animals fed control chow and those fed the atherogenic diet. Furthermore, insulin supplementation given to diabetic rats caused a reduction of enzyme activity to the levels found in control animals. In contrast, cholesterol esterase activity in rat intestinal mucosa was unaffected by either the induction of diabetes or the atherogenic diet feeding. In conclusion, we disclosed that apparent ACAT activity in intestinal mucosa is elevated in STZ-D rats. Therefore, we postulate that enhancement of CoA-dependent cholesterol esterification in the intestine might be one of the major factors responsible for hypercholesterolemia in diabetes.
Diabetes 1988 Mar
PMID:Increased activity of intestinal acyl-CoA: cholesterol acyltransferase in rats with streptozocin-induced diabetes and restoration by insulin supplementation. 296 15

1. Hyperlipidaemia is associated with diabetes mellitus. 2. A comparison of cholesterol synthesis and utilization in alloxan-induced diabetic rats and rabbits revealed that interspecies differences existed only in the response of the key enzymes regulating cholesterol utilization, namely cholesterol 7 alpha-hydroxylase and ACAT in the liver and intestine respectively. 3. The activity of cholesterol 7 alpha-hydroxylase was enhanced in diabetic rats but was markedly reduced in diabetic rabbits. 4. Intestinal ACAT activity, though unchanged in diabetic rats was reduced in diabetic rabbits. 5. Such species differences in cholesterol utilization may underlie the different degree of susceptibility to hypercholesterolaemia that exists between these two species.
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PMID:A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the alloxan-induced diabetic rat and rabbit. 342 2

There is a very high probability that lipoprotein metabolism plays a central role in the etiology of coronary heart disease. In sedentary persons one way to favorably alter lipoprotein metabolism and possibly delay the progression of coronary atherosclerosis is by an increase in their habitual physical activity. More physically active persons tend to have lower plasma triglycerides and very low density lipoprotein concentrations, and a greater high-density lipoprotein mass due to higher concentrations of the subfraction HDL2 and apoprotein A-I. Plasma low-density lipoprotein concentrations usually are not significantly reduced by exercise unless accompanied by weight loss, but there may be important changes in the distribution among the low-density subfractions. These exercise effects are most likely mediated by alterations in the activity of enzymes involved in the synthesis, transport and catabolism of the various lipoproteins including lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase. In healthy persons as well as in patients with ischemic heart disease, diabetes and renal failure, an increase in moderate-intensity, endurance-type activity requiring an expenditure of approximately 4 MJ (1,000 kcal) per week usually produce favorable lipoprotein changes. Above this level a dose-response relationship exists, with greater changes occurring up to energy expenditures of 19 MJ (4,500 kcal) per week.
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PMID:The influence of exercise training on plasma lipids and lipoproteins in health and disease. 353 12

Lecithin cholesterol acyltransferase (LCAT) appears to be one of the factors controlling the intravascular turnover rate of cholesterol. LCAT activity in healthy subjects is significantly higher in men than in women of the same relative body weight, total and free cholesterol and triglycerides. In healthy men sleep deprivation induced a decrease in LCAT activity combined with a decline of serum cholesterol concentration; consequently, the intravascular turnover rate of cholesterol did not significantly change. In hypertensive patients the decrease in cholesterol turnover rate correlated with the degree of hypertension and the response of blood pressure to medication. Reduced turnover rate of cholesterol was more frequent in men than in women, in spite of higher plasma cholesterol concentration in the latter. During a 4-month period of treatment etiroxate of hyperlipoproteinemia II and IV, the only significant change in plasma cholesterol level was a drop observed after the first two weeks; on the other hand, the turnover rate of cholesterol rose gradually and approached normal values due to a highly increased LCAT activity. Obesity and diabetes were associated with a high percentage of deviations in the studied parameters of cholesterol metabolism. The turnover rate of cholesterol measured three months after acute myocardial infarction was below normal in 80% of patients, whereas hypercholesterolemia was manifested in only less than 40%. The results imply that the intravascular turnover rate of cholesterol estimated by measurement of LCAT activity may be a suitable indicator of the internal balance of cholesterol, substantially more delicate and discriminative than a mere determination of the actual plasma concentration of cholesterol or plasma lipoprotein. Judging by our observations, deviations in the internal dynamics of cholesterol may play an important role in the pathogenesis of coronary atherosclerosis.
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PMID:Cholesterol turnover and risk factors for the development of coronary heart disease. 707 90


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