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H Ditschuneit

Publications and source records attributed to H Ditschuneit.

At least 181 records · Page 10Linked to original sources
PubMed1981

Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase by endogenous sterol synthesis in cultured intestinal mucosa.

In vitro regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) by compactin, a competitive inhibitor of the enzyme, and mevalonate was studied in rabbit ileum organ culture. Addition of compactin suppressed ileum homogenate reductase activity by over 80% at concentrations up to 0.5 microgram/ml. In contrast, compactin at the same concentrations added to the culture medium induced reductase activity up to 240% of controls. This increase was blocked by cycloheximide and mevalonolactone at 10 mM, but not by mevalonate (salt form) and cholesterol. Similarly, in contrast to ionized mevalonate, mevalonolactone significantly suppressed reductase activity of cultured intestine at 1 and 10 mM by 23 and 62%, respectively. A minor effect was also observed with preformed enzyme in fresh mucosal homogenate. When endogenous cholesterol synthesis was blocked by compactin, mucosal alkaline phosphatase activity decreased progressively, whereas medium activity from desquamated cells did not change. This distribution of the villous cell marker enzyme is characteristic of a decrease in crypt cell renewal and/or villous cell differentiation. This effect of compactin was also reversible with mevalonolactone. The reductase enzyme induced by compactin was probably latent intracellularly, since tissue cholesterol contents dropped sharply after blockade of endogenous sterol synthesis.

Alkaline Phosphatase↗
PubMed1981

Effect of insulin on growth of cultured human arterial smooth muscle cells.

The effect of insulin (10--10 000 mU/1) on the proliferation of cultured human arterial smooth muscle cells was studied. Smooth muscle cells were cultivated by explanation. Cells from the third to the fifth subculture were used. Proliferation was studied by growth curve experiments. Insulin stimulated cell proliferation in all concentrations (p less than 0.001). Growth was however stimulated more by a medium containing 10% fetal calf serum. The highest concentration of insulin produced only 35% of the effect of 10% fetal calf serum. Our results support the hypothesis that insulin may play a role in atherosclerosis.

Adult↗
PubMed1981

Regulation of 3-hydroxy-3-methylglutaryl CoA reductase by analogs of cholesterol and bile acids in cultured intestinal mucosa.

Sodium fusidate and its glycine conjugate, which have the same detergent properties as bile acids, significantly (p less than 0.05) stimulate HMG-CoA reductase of cultured intestine below the critical micellar concentration (CMC) without affecting brush border enzymes. Above CMC, both amphiphiles are cytotoxic. At concentrations between 1 and 5 mM, sodium fusidate decreased cholesterol contents of cultured mucosa (P less than 0.05), the increase in synthesis only partially compensating for the sterol loss. Oxygenated sterols, 7-keto- and 25-hydroxycholesterol, also depleted mucosal cholesterol at 0.5 mM, exerting their effect differently by inhibiting HMG-CoA reductase (p less than 0.01). In contrast to their marked effect on total mucosal cholesterol contents, brush border cholesterol was unaffected by both cholesterol and bile acid analogs.

Animals↗
PubMed1981

Characterization of beta-adrenergic receptors by (3H) isoproterenol in adipocytes of humans and rats.

The specific binding of (3H) isoproterenol to isolated fat cells of human and rat was characterized. Binding of (3H) isoproterenol to isolated fat cells of rat was saturable with 420 pmol of (3H) isoproterenol bound/100 mg of lipid. Half-maximal saturation occurred at 5 microM providing an estimate of the equilibrium dissociation constant, KD, for the interaction of (3H) isoproterenol with its binding sites. Kinetic analysis of (3H) isoproterenol binding provided a value of 2.01 x 10(4) min-1. M-1 for the forward bimolecular rate constant, k1. Dissociation of (3H) isoproterenol was a first order reaction with a rate constant, k2, of 0.62 x 10(-1) min-1. The ratio k2/k1 = 3.07 microM provides an independent measurement of the KD for the interaction of (3H) isoproterenol with its binding sites which is in agreement with the values obtained by steady state analysis (3 to 5 microM). The apparent equilibrium dissociation constant, KD, for the interaction of (3H) isoproterenol with its receptor in human fat cells obtained by steady state analysis was 1 to 0.9 microM. Scatchard- and Hill-analysis suggest the possibility of different negatively cooperative interactions among the binding sites in human and rat. beta-Adrenergic agonists competed for the binding sites. The order of potency was isoproterenol greater than epinephrine greater than norepinephrine. Compounds such as DOPA, dopamine and (m-Hydroxyphenyl)2-methyl-aminoethanol which are structurally related to catecholamines had little or no affinity for (3H) isoproterenol binding sites.

Adipose Tissue↗
PubMed1981

Thyroid hormone effects on beta-adrenergic receptors in isolated fat cells in rats.

The effect of thyroid hormones (thyroxine and triiodothyronine) on catecholamine receptors in isolated rat fat cells was investigated. Binding of (3H)isoproterenol and (3H)norepinephrine were increased by thyroid hormones. (3H)isoproterenol binding was more enhanced than (3H)norepinephrine binding. Triiodothyronine had a more potent effect than thyroxine. (3H)isoproterenol was used to estimate the number or affinity of beta-adrenergic receptors in rat fat cells treated with thyroid hormones. The binding sites for (3H)isoproterenol were the same in untreated and with triiodothyronine treated fat cells. The equilibrium dissociation constants (KD) for the interaction of receptors with (3H)isoproterenol were altered in thyroid hormone treated cells. There was a significant difference between the untreated and triiodothyronine treated fat cells in the affinity of beta-adrenergic receptor binding sites for (3H)isoproterenol. Thyroid hormone could alter negative cooperative site-to-site interaction among the binding sites for (3H)isoproterenol.

Adipose Tissue↗
PubMed1981

[Gastric acid and parotid secretion in obesity [greater than 55%] (author's transl)].

In order to investigate exocrine secretory activity in obesity we studied gastric acid and parotid secretion in 22 massively obese patients (greater than 55% overweight); 15 normal persons were taken as controls. Basal and stimulated secretory values were determined. Basal acid output (BAO) in the obese (4,10 +/- 3,8 mval/h) was higher compared to normal (1,98 +/- 1,59 mval/h); the amylase activity in parotid saliva was reduced in the obese means = 195 U/ml (93,8-406) compared to normal means = 307 U/ml (145-652). These differences were not statistically significant. Maximal acid output (MAO) in the obese was within the normal range 17,6 +/- 8,98 mval/h (norm 16-25) despite it was expected, in a weight related manner, to be in a strongly hypersecretory range.

Adolescent↗
PubMed1981

Influence of dietary cholesterol, saturated and unsaturated lipid on 3-hydroxy-3-methylglutaryl CoA reductase activity in rabbit intestine and liver.

To characterize further the behavior of the rate-limiting enzyme of cholesterol biosynthesis in animal species, we studied the kinetic properties and the influence of dietary lipid on intestinal and hepatic HMG-CoA reductase activity in the rabbit. In intestinal crypt and villous cells isolated by a dual buffer technique, the KM value was 4.2 and 4.6 microM, respectively for DL-HMC-CoA. The specific activity of HMG-CoA reductase in the jejunum was 0.86 nmol/mg per hr, and evenly distributed between crypt and villous cells. By contrast, reductase activity was considerably lower in the ileum: in villous cells it was 0.40 nmol/mg per hr, and in crypt cells only 0.26 nmol/mg per hr. Liver microsomes had a KM value of 3.0 microM, while the reductase activity averaged 2 nmol/mg per hr. An unexpected finding was the uneven distribution of HMG-CoA reductase in the various lobes of the liver in the single animal. The addition of 1% cholesterol to the diet for 48 hours was followed by an average decline of 73% (P less than 0.005) of HMG-CoA reductase activity in villous and crypt cells of the jejunum. In the ileum, the decrease was less marked (38%, P less than 0.01). Whereas the addition of 5% corn oil to a 1% cholesterol diet did not have an additional suppressant effect on intestinal reductase, the addition of 5% coconut oil to 1% cholesterol caused further decrease of HMG-CoA reductase in jejunum and ileum (P less than 0.05). The 1% cholesterol diet resulted in a 25% decrease of hepatic reductase after 24 hours, whereas after 6 days, the enzyme activity was reduced by 90% of normal. Both 5% corn oil or 5% coconut oil, in addition to 1% cholesterol, further suppressed hepatic reductase activity. The weight of the experimental evidence presented in these studies suggests that cholesterol has a major regulatory effect on both intestinal and hepatic reductase in the rabbit.

Animals↗
PubMed1980

Lipoprotein regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured intestinal mucosa.

In vitro regulation of the key enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34), was studied in 24-h organ culture of rabbit ileum. Preincubation of mucosal homogenate in phosphate buffer increased apparent reductase activity more than 5-fold. The activation was blocked in the presence of 150 mM NaF, suggesting interconversion of latent reductase by dephosphorylation. No significant further activation was achieved by potato phosphatase treatment. During culture total reductase activity was stimulated by 125% in lipoprotein-free medium. Addition of low density lipoprotein to the medium resulted in a dose-dependent suppression of reductase activity between 0.2 and 1.0 mM lipoprotein cholesterol. At these concentrations LDL inhibition reached 51 and 75% of control, respectively. The reductase response to very low density and high density lipoproteins was biphasic, with a 2- to 3-fold stimulation at 0.1-0.3 mM and a suppression at higher levels. No such stimulation was observed with high density lipoproteins obtained from cholesterol fed animals. Similarly, 'hypercholesterolemic' very low density lipoproteins enhanced reductase activity only slightly. It is concluded that lipoproteins are potent regulators of cholesterol synthesis in cultured intestine.

Animals↗
PubMed1980

[Nitrogen balance during modified fasting (author's transl)].

Protein-substituted or protein-saving modified fasting (PSMF) is intended to prevent high protein loss during total fasting by use of low-dose substitution. 27 obese in-patients were treated over a period of four weeks with modified fasting. The daily amount of protein substituted was 33 g on an egg-white base (Modifast). As in total fasting the nitrogen balance of the first and second week was negative, balanced in the third week and positive in the fourth. The total balance over 4 weeks was negative with a nitrogen loss of 70.7 g N, equivalent to a protein loss of 442 g (lean body mass). Nitrogen and protein loss in PSMF over 4 weeks was only a third of the loss in total fasting (-183.2 g N equivalent to 1145 g protein). Protein-substituted modified fasting may be used for more than 4 weeks as nitrogen balance is stabilised as from the third week, and remained so until the end of the observation period of 8 weeks.

Adolescent↗
PubMed1980

Insulin as a cellular growth regulator of rat arterial smooth muscle cells in vitro.

Smooth muscle cells were grown from thoracic aortas of rats. The effect of insulin on the proliferation of these cells was studied by comparing the growth of cells in culture medium containing insulin and 1% fetal calf serum with growth of cells in culture medium containing only 1% serum and in culture medium containing 10% serum. Insulin in concentrations of 10, 50, 100, 1000 and 10 000 microunits/ml induced smooth muscle cells to stationary growth more rapidly than basal medium. This could be demonstrated as well in the logarithmic growth as in confluent cells grown in medium with 1% serum. However, the highest concentration of insulin did not stimulate growth to the same degree as medium containing 10% serum. Cells that were older in culture life (11th passage) did not show a growth response to insulin.

Animals↗
PubMed1980

Thyroid hormone stimulation of lipolysis and cyclic adenosine 3', 5'-monophosphate accumulation in human adipose tissue.

The role of thyroid hormones on lipolysis in human subcutaneous adipose tissue was investigated. Incubation of subcutaneous fat pads with thyroxine (0.1--10 000 nM) augmented the subsequent isoproterenol stimulation of lipolysis, measured by glycerol release. The basal lipolysis could not by stimulated by thyroxine. The theophylline- and dibutyryl-cyclic AMP stimulated lipolysis also could not be increased by thyroxine at these concentrations. In separate studies, the effect of thyroxine (0.01 pM--1 microM) and triiodothyronine (0.01 pM--1 microM) on cyclic AMP accumulation was examined. No effect of thyroid hormones on cyclic AMP accumulation was seen in non-isoproterenol stimulated tissue. Fat pads stimulated by isoproterenol and then treated with thyroid hormones showed marked increases in accumulation of cyclic AMP as compared to control tissue in the presence of isoproterenol alone.

Adipose Tissue↗
PubMed1980

The effect of insulin and insulin-like growth factors on cell proliferation of human smooth muscle cells.

The effect of insulin and insulin like growth factors on the proliferation of cultured human arterial smooth muscle cells was investigated. Smooth muscle cells were cultivated by explanation. The effect of insulin and of an isolated serum protein fraction containing insulin like growth factors on the proliferation of human arterial smooth muscle cells was studied by incorporation of 3H-thymidine into DNA of the cells. Insulin stimulated in all concentrations the proliferation of the cells more than culture medium with 1% fetal calf serum. Insulin could not stimulate growth to the same degree as medium with 10% serum. On the other hand the isolated proteins had a more potent growth-promoting effect than medium with 10% serum.

Arteries↗
PubMed1980

[Effect of etofylline clofibrate on the composition of lipoproteins in hyperlipidaemia type IIb and IV (author's transl)].

Efficacy of 1-(theophyllin-7-yl)-ethyl-2[2-(p-chlorophenoxy)-2-methylpropionate] (etofylline clofibrate, Duolip) (3 x 250 mg) was evaluated in a double-blind cross-over study in 20 patients of type 11b (10 and type IV (10) in comparison to a commercial drug combination (= standard preparation) of clofibrate (3 x 500 mg) and beta-pyridylcarbinol hydrogentartrate (3 x 25 mg). This standard preparation was known from clinical results to be superior over clofibrate in antilipaemic potency. All patients had been already on a diet for several months and in majority were additionally treated with antihyperlipaemic drugs. The treatment periods lasted over 8 weeks each. They were introduced by placebo phases of 4 weeks duration. Between the treatment periods with etofylline clofibrate and with the standard preparation, placebo phases of 4 weeks were inserted, too. The results indicate, that between etofylline clofibrate and the standard preparation there are no remarkable differences and thus 750 mg etofylline clofibrate correspond to 1500 mg clofibrate combined with 75 mg beta-pyridylcarbinol hydrogentartrate in their efficiencies. Since the clofibric acid proportion of etofylline clofibrate clinically is known as ineffective we postulate a potentiation of its effect by its metabolits to cause this surprising effect. In type IIb the cholesterol was distinctly decreased in the VLDL-fraction by 22% and significantly increased in the HDL-fraction by 22%. In type IV triglycerides and cholesterol dropped in the VLDL by 11% and 16%, resp., unless the LDL-fraction revealed an increase of the lipid content. The lipids of the HDL-fraction did not show any essential alternations. Side effects were not observed. The investigations prove that etofylline clofibrate is suitable for the treatment of hyperlipoproteinaemia with elevated triglycerides and cholesterol.

Adult↗