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B Elsenhans

Publications and source records attributed to B Elsenhans.

50 records · Page 3Linked to original sources
PubMed1986

Comparison of the effect of two different hypoglycemic agents, glibenclamide and HB 699, on the rat small intestinal absorption of sugars and amino acids.

4-(2-[5-Chloro-2-methoxy-benzamido]-ethyl)-benzoic acid (HB 699) belongs to the group of hypoglycemic benzoic acid derivatives. Although lacking the sulfonylurea group, the structure of HB 699 partly resembles that of glibenclamide which is known to impair small-intestinal glucose absorption in vitro at high concentrations. Whereas this intestinal effect of glibenclamide is unlikely to contribute to its blood-glucose lowering properties, extrapancreatic and particularly intestinal effects may be important for the antidiabetic action of HB 699. Thus, HB 699 was compared with glibenclamide for the effect on the small-intestinal absorption of sugars and amino acids in vitro (everted-sac and tissue-accumulation technique) and in vivo (single-pass perfusion of the jejunum). In vitro both drugs inhibited the active transport of sugars and amino acids in a dose dependent manner. At equieffective doses (HB 699, 4.5 mmol/l and glibenclamide, 1 mmol/l) the mode of inhibition by the two drugs was similar. A 30-min incubation period reduced the uptake of methyl alpha-D-glucoside by about 75%. The degree of inhibition depended on the time of exposure of the tissue to the drugs. In vitro kinetic studies revealed a mixed type of inhibition. The in vivo effect of the drugs was in accordance with the in vitro findings. Inhibition, as in vitro, was not reversible and even increased further after reinfusion of a drug-free perfusate. In vivo, the drugs inhibited the absorption of methyl alpha-D-glucoside and leucine only at low (less than 20 mmol/l) but not at high (greater than 30 mmol/l) solute concentrations. These results indicate that hypoglycemic benzoic acid derivatives may exert their blood-glucose lowering properties in part by impairing the small-intestinal active transport of glucose.

Amino Acids↗
PubMed1985

In vitro inhibition of rat small intestinal absorption by lipophilic organic cations.

Cationic, lipid-soluble organic compounds may interfere with cation-mediated membrane transport processes. Thus, small intestinal absorption may be influenced by lipophilic organic cations. Therefore a series of arylalkylamines was studied in the concentration range from 0.5 to 20 mmol/l for their effect on the transport of various monosaccharides and leucine in the rat small intestine in vitro by means of the tissue accumulation technique. Whereas the monophenyl substituted monoamines (e.g. benzylamine, 2-phenylethylamine, 3-phenylpropylamine) did not show a significant effect on the active transport, the corresponding omega,omega-diphenyl derivatives exhibited a strong inhibition of the active transport of the sugars and the amino acid. These monoamines and drugs of similar structure (e.g. benzoctamine, diphenydramine) exhibited a mixed or non-competitive type of inhibition which correlated quite well with their octanol-water partition coefficients. In contrast, di- or triamines (e.g. harmaline, imipramine, pyrilamine) revealed a rather pure competitive type of inhibition. These findings tentatively suggest a different mode of action on the active transport by lipid-soluble organic amines according to the molecular charge distribution. In addition, membrane vesicles were used to examine the effect of the different amines on the sucrase activity. Regarding the cation-dependent hydrolysis of sucrose, however, no distinct pattern developed.

Animals↗
PubMed1985

Iron retention and distribution in the cadmium-induced iron deficiency.

The retention and distribution of iron-59 after oral administration of a single iron dose in the presence and absence of various cadmium doses were tested in normal rats acutely or subchronically treated with various amounts of dietary cadmium (28, 56, 112 ppm). In a second series of experiments the kinetic parameters (Km and Vmax) of iron absorption were estimated in normal and iron-deficient rats after oral administration and from tied-off jejunal and duodenal segments. In acute experiments the retention of iron decreased inversely with respect to the cadmium dose administered simultaneously. After subchronic exposure to dietary cadmium for 4 weeks the retention of iron was increased if iron was administered alone or together with cadmium in comparison to normal controls. If iron was administered alone to subchronically treated animals, iron retention was of the same order of magnitude as in iron-deficient controls. However, if iron was administered together with cadmium (molar ratios 1/0.5, 1/1, 1/2 mumol/kg body wt) the retention of iron was decreased in a dose-dependent manner. The iron content in the liver and spleen of acutely exposed rats decreased, whereas the tissue content of the treated rats increased according to the increased body retention of iron. The utilization of iron for hemoglobin synthesis remained unchanged in all groups investigated.

Anemia, Hypochromic↗
PubMed1985

Adaptation of the small intestine to induced maldigestion in rats. Experimental pancreatic atrophy and acarbose feeding.

Intestinal adaptation has been studied in rats with pancreatic atrophy induced by feeding a copper-deficient diet and penicillamine and in rats with carbohydrate maldigestion induced by feeding of an alpha-glucosidase inhibitor (acarbose). Pancreatic atrophy led to a significant increase of weight, protein, and DNA content as well as specific activities and total amounts of the enzymes sucrase and maltase in the distal but not in the proximal part of the small intestine. Plasma levels of CCK and GIP were significantly higher in rats with pancreatic atrophy, whereas plasma levels of gastrin and insulin were lower. Tissue concentrations of gastrin in the antrum and GIP in duodenum and jejunum were unchanged. Duodenal CCK and jejunal substance P, somatostatin, and VIP and ileal substance P and somatostatin were significantly decreased in rats with acinar atrophy. Glucosidase inhibition by acarbose feeding led to weight increase of the small intestine and cecum. This was more marked when acarbose was fed together with a fiber-free diet. Under these conditions the protein and DNA content also increased significantly in both gut segments and maltase and sucrase content predominantly in the distal part. Insulin plasma concentration decreased significantly in the acarbose-fed groups, whereas GIP, gastrin, and CCK plasma concentrations remained unchanged. After fiber-rich diet tissue concentrations of gastrin in the antrum and insulin in the pancreas were significantly higher and GIP concentrations in the duodenum and jejunum significantly lower than after fiber-free diet. Acarbose increased the pancreatic insulin concentration only in the fiber-free group and did not influence gastrin and GIP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗
PubMed1984

Isolation and characterization of pteroylpolyglutamate hydrolase from rat intestinal mucosa.

Pteroylpolyglutamate hydrolase was isolated from rat intestinal mucosa and purified with the aid of affinity chromatography. The affinity ligand was poly-gamma-glutamic acid (Mr approximately 12,000) derived from Bacillus subtilis. The specific enzymatic activity was increased 2,000-fold over the 100,000 X g supernatant of the mucosal homogenate with a yield of 20%. Sephadex G-200 gel filtration yielded an estimated molecular mass of 80,000 daltons. The isoelectric point was pH 8.2. The pH optimum in acetate buffer containing 1 mM zinc was 4.5. The KM values for pteroylheptaglutamate and pteroyltriglutamate were 0.21 and 0.67 microM, respectively. Polyanionic compounds, poly-gamma-glutamic acid, dextran sulfate, and heparin were noncompetitive inhibitors. Studies of the time course of hydrolysis of synthetic [3H]pteroylheptaglutamate by three separate techniques demonstrated the appearance of [3H]pteroylmonoglutamate, synchronous with substrate cleavage. Intermediate pteroyloligoglutamates were not detected. An endopeptidase-like mode of hydrolysis was further established by identification of a hexaglutamyl peptide as the other reaction product.

Animals↗
PubMed1984

Influence of metal substitution on vitamin B12 binding to human intrinsic factor and transcobalamins I and II.

Metal-free, zinc, copper, and rhodium analogues of vitamin B12 were synthesized to further characterize structural requirements for the binding to human intrinsic factor, transcobalamin I, and transcobalamin II. Binding affinities of the various analogues were studied by competition against cyano[57Co]cobalamin. When albumin-coated charcoal was used for the separation of free and bound corrinoids, the relative 50% inhibition indexes were determined. The influence of metal substitution was similar among the three binding proteins. For analogues with a strong coordinative linkage between the heterocyclic base and the central metal ion, similar to that with cobalt (e.g., zincobalamin and cyanorhodibalamin), the indexes range from 0.65 to 2.35 for all three binding proteins. Analogues in which coordination is impossible (hydrogenobalamin and dicyanorhodibalamin) exhibit markedly reduced binding with indexes between 10 and 160. Cupribalamin shows 50% inhibition indexes ranging from 2.3 to 5.0, thus suggesting a weak coordinative bond between the copper ion and the 5,6-dimethylbenzimidazole moiety. These results emphasize the importance of the coordinative linkage between the central metal ion and the nucleotide moiety for optimal recognition by vitamin B12 binding proteins.

Binding Sites↗
PubMed1984

Guaran effect on rat intestinal absorption. A perfusion study.

Among the components of dietary fiber, the soluble polysaccharides, primarily guaran and pectin, have been found to impair intestinal absorption. Little is known, however, about the mechanism of this effect. The direct action of guaran on small intestinal absorption was evaluated by a single-pass perfusion technique. Guaran in the perfusate (1-7 g/L) inhibited small intestinal absorption of actively transported compounds, such as alpha-methyl-D-glucoside, cycloleucine, and taurocholate, and also of the passively permeating solutes 2-deoxy-D-glucose and urea. Viscosity-related inhibition by guaran was found to depend on the rate of perfusion and was only detectable at perfusion rates below 0.4-0.5 ml/min. Higher perfusion rates abolished and even reversed the inhibitory effect. The observed alterations of absorption rates caused by guaran were completely reversible after switching to a guaran-free perfusate. The concentration-dependent absorption of D-glucose and alpha-methyl-D-glucoside at perfusion rates of 0.4 and 0.2 ml/min, respectively, revealed an increase in the transport constant and essentially unaltered maximal transport capacity in the presence of guaran. Additionally, net water absorption changed to secretion upon addition of guaran. When pectin and carrageenan were used in solutions of comparable viscosity, their effect was similar to that of guaran. The results suggest a general mechanism by which soluble, viscosity-enhancing polysaccharides influence the intestinal absorption of nutrients. The most likely explanation appears to be an increase in the unstirred layer resistance to diffusion. Under our experimental conditions, this occurred at low perfusion rates, but was increasingly counteracted by raising the rate of perfusion.

Animals↗
PubMed1983

A new class of inhibitors for in vitro small intestinal transport of sugars and amino acids in the rat.

Polycationic compounds like polylysine, protamine or polyethylenimine may interfere with a cation-related membrane transport system depending on superficially accessible binding sites for particular cations. In vitro experiments were performed using either everted segments of rat small intestine to measure tissue accumulation or everted sacs to determine mucosal-to-serosal transport. The effect of polycations was also tested using brush-border membrane vesicles of rat jejunum. Polycations inhibited the tissue accumulation of methyl alpha-D-glucoside as well as binding of phlorizin. Inhibition of accumulation was increased by raising the polycation concentration and by preincubation of the tissue with the polycations. Kinetic experiments revealed a competitive type of inhibition for the uptake of neutral amino acids and actively transported sugars. Using everted sacs to compare the monomeric cations with their corresponding polymeric forms for their inhibitory effect, it was found that only polymers applied to the mucosal compartment impaired active transport. The passive diffusion of solutes, e.g. 2-deoxy-D-glucose or mannitol, was slightly increased by polycations. With some intermediate oligomers of lysine it could be shown that more than 20 cationic groups are required for approximate complete inhibition. That membrane-related events are responsible for the observed inhibition is suggested by the reduced uptake of D-glucose by brush-border membrane vesicles in the presence of polycations. Therefore an interaction with transport-related cation binding sites, i.e. anionic residues, at the mucosal surface may be assumed.

Animals↗
PubMed1981

Long-term feeding of unavailable carbohydrate gelling agents. Influence of dietary concentration and microbiological degradation on adaptive responses in the rat.

Guaran, tragacanth, gum arabic, carrageenan, gum karaya, and methylcellulose were used in a long-term feeding study to evaluate their effects upon adaptive responses of nutritionally controlled parameters in rats by feeding a fiber-free diet containing increasing additions of polysaccharides. In general, supplements reduced weight increases due to lower energy intakes. Only in the case of microbiologically inert polysaccharides the dilution of the the energy density was partially compensated by an increased food intake. Neither of the polysaccharides fed, however, decreased energy utilization. All polysaccharides similarily increased small intestinal length up to about 30% without grossly altering mucosal protein and DNA per unit of length. Concerning their effects on the colon and the cecum, polysaccharides behaved differentially according to their accessibility to microbiological degradation. Inert polysaccharides exerted a more pronounced effect on the colon whereas the others mainly increased cecum weight. Degree and locus of the observed changes are determined mainly by the dietary concentration of the polysaccharides and their accessibility to bacterial degradation within the intestinal tract.

Adaptation, Physiological↗
PubMed1981

In vitro inhibition of rat intestinal surface hydrolysis of disaccharides and dipeptides by guaran.

The effect of guaran on intestinal surface hydrolases was studied in everted jejunal segments by measuring the hydrolysis of maltose and phenylalanylglycine. On the basis of kinetic experiments, guaran was found to inhibit competitively the hydrolysis of these substrates only if the cleavage was performed with intact tissue. Hydrolysis in mucosal homogenates was not affected by guaran, indicating that this polysaccharide may increase the diffusion barrier overlaying the mucosa and thus may retard final digestion of carbohydrates and peptides.

Animals↗
PubMed1980

The influence of carbohydrate gelling agents on rat intestinal transport of monosaccharides and neutral amino acids in vitro.

1. In the present investigation with rings of everted rat small intestine, carbohydrate gelling agents (plant polysaccharides) such as guaran, pectin, tragacanth, carubin and carrageenan were employed to study their direct effect on intestinal absorption of alpha-methyl-D-glucoside, D-galactose, L-leucine and L-phenylalanine. 2. Inhibition was found to correlate with the viscosity of the incubation medium, a function only of the polysaccharide concentration, and was independent of other properties of the carbohydrate gelling agents. 3. Reversal of this inhibition was achieved either by washing the tissue free of polysaccharide or by raising tissue agitation. 4. Uptake kinetics in polysaccharide-containing solutions revealed a marked increase of the apparent Michaelis constant although the maximal transport capacity remained essentially unaltered. 5. Since there was no binding of the substrate by the polysaccharides under experimental conditions as judged by a membrane filtration technique, it is concluded that carbohydrate gelling agents may impair intestinal absorption by means of an increased unstirred layer resistance.

Amino Acids↗
PubMedDate not supplied

The longitudinal distribution of cadmium, zinc, copper, iron, and metallothionein in the small-intestinal mucosa of rats after administration of cadmium chloride.

Different routes of Cd intake may influence the intestinal distribution of Cd, metallothionein (MT), and trace metals differently. Therefore, we compared the effects of parenteral and enteral administration of Cd on the distribution of trace metals and MT along the small intestine. In a first experiment three groups of rats were employed: a control, one receiving CdCl2 within the drinking water, and another receiving sc injections of CdCl2. In a second experiment, rats were fed three different diets with either 0, 0.3, or 1 mmol CdCl2/kg for one and two weeks to study the time- and dose-dependent effects of orally administered Cd. Metal concentrations (Cd, Zn, Cu, Fe) were measured by atomic emission spectrometry and MT was determined by radioimmunoassay. Intestinal MT levels did not show proximodistal gradients in controls or after sc administration of Cd, but orally administered Cd increased mucosal MT levels longitudinally from the duodenum to the ileum. Cd levels paralleled those of MT. Compared with the metal concentrations in the controls, sc administration of Cd did not change intestinal Zn, Cu, and Fe levels. Oral administration of Cd, however, increased Cu and decreased Fe levels in the intestinal mucosa significantly. The second experiment revealed that only high dietary concentrations of Cd increase intestinal Cd and MT levels longitudinally toward the distal parts, whereas at lower dietary concentration the longitudinal distribution was reversed. This shows that different routes and doses of Cd intake lead to a different trace metal and MT distribution and emphasizes the role of dietary Cd in the local induction of small-intestinal MT.

Administration, Oral↗