[Dietary fiber--physiological effects and medical applications].
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Biomedical subjects
Publications and source records attributed to Z Madar.
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OBJECTIVES: The cellular mechanism(s) of insulin resistance developed during pregnancy were studied by investigating the functionality of insulin receptors and glucose transport. STUDY DESIGN: Abdominal adipose tissue was obtained from eight lean pregnant and nine control subjects, matched for insulin resistance by intravenous glucose tolerance testing. Insulin receptor binding and glucose transport were measured in freshly isolated adipocytes. Receptor kinase activity was measured on partially purified receptors. Data were analyzed by Student t test. RESULTS: High-affinity insulin receptors were reduced in cells from pregnant compared with normal controls (2.0 +/- 0.4 vs 5.8 +/- 1.3 x 10(4) sites per cell, p < 0.05). Kinase activity of insulin receptors was unaltered in pregnancy. Adipocytes from pregnant subjects displayed a threefold decrease in insulin sensitivity for glucose transport (median effective concentration 324 +/- 93 vs 93 +/- 14 pmol/L, p < 0.025) and a reduction in maximal insulin-stimulated glucose transport (1.58 +/- 0.15 vs 2.33 +/- 0.24 pmol/10(5) cells/10 seconds, p < 0.025). CONCLUSIONS: These results show that adipocytes from pregnant subjects exhibit decreased insulin receptor number and an impaired insulin sensitivity in the absence of functional alterations of receptor kinase activity.
Sand rats were used as a model for nutritionally induced type II (non-insulin-dependent) diabetes in an effort to evaluate the effect of acarbose on carbohydrate digestion. Daily plasma glucose profiles, insulin levels and weekly cararact development were determined following long-term feeding with a diet containing acarbose (20 or 40 mg/100 g diet). Acarbose not only dramatically decreased daily plasma glucose and insulin levels (p < 0.05) but also delayed, and possibly prevented, cataract formation in sand rats. The effect of acarbose persisted for 150 days. The control of daily plasma glucose levels and reduction of insulin levels obtained with acarbose may lead to the delay of cataract formation in sand rats. These results could have potential applications to diabetic patients as an adjunct treatment.
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The hypocholesterolaemic properties of an ethanol extract from defatted fenugreek (Trigonella foenum-graecum) seeds were investigated. Purification of the crude extract by dialysis produced an isolated component with haemolytic properties. The dialysate was also found to contain saponins demonstrated by thin-layer chromatography. Experiments in vitro employing the everted-sac technique showed that the ethanol extract had the ability to inhibit taurocholate and deoxycholate absorption in a dose-dependent manner. In two separate feeding experiments, hypercholesterolaemic rats were fed on 30 or 50 g ethanol extract/kg for a 4-week period. Reductions in plasma cholesterol levels ranged from 18 to 26% and a tendency for lower concentrations of liver cholesterol was observed. These results indicate that the ethanol extract from fenugreek seeds contained hypocholesterolaemic components which appear to be saponins that interact with bile salts in the digestive tract.
The protective role of dietary fibers on tumorigenic effects of 1,2-dimethylhydrazine (DMH) on the rat colon was studied using histochemical, immunohistochemical, and biochemical analyses. Rats were injected with DMH (20 mg/kg sc) for five weeks, once a week, and were fed laboratory chow (Control I), semisynthetic fiber-free diet (Control II), or 18% or 25% assorted fiber (cellulose, beans, corn) diet. The rats were sacrificed 12, 16, and 24 weeks after the carcinogenic injections. Adenomatous tumors developed in 90-100% of the animals fed chow or fiber-free diets. A diet with high concentrations (25%) of corn dietary fiber significantly decreased the tumor incidence (40% and 42%) and tumor yield (p < 0.01). Diets with lower concentrations of fibers (18%) did not protect against tumorigenic effects of DMH. No differences were found in pathological parameters of tumors obtained from different dietary groups: the damage index (percentage of damaged cells per section) was very similar in all groups studied. Diets enriched with dietary fibers (25%) had a significant protective effect in DMH-induced rat colon cancer.
In this study we analyzed a commercial dietary fiber blend known as Fiber-Plus and a dietary fiber mixture (DFM) prepared in our lab (10% apple pectin, 10% orange pectin, 36% locust bean gum and 44% corncob composed of 56% fiber). DFM provided greater inhibition of starch digestion and glucose absorption (p < 0.05) than did Fiber-Plus. DFM was also found to be significantly more efficient (p < 0.05) than Fiber-Plus at reducing the glycemic response following starch loading. Rats fed DFM or corncob demonstrated a much lower glycemic response following a test meal as compared to those fed a fiber-free diet. Both fiber sources decreased fasting cholesterol and triglyceride concentrations; transit time was shortened and fecal values were higher than those of controls. beta-glucuronidase activity in intestinal segment contents and feces was lower in rats fed fiber. We conclude that DFM is effective in controlling plasma glucose and lipid levels. Corncob, a novel fiber source, could be beneficial in the treatment of gastrointestinal tract disorders and in the elimination of carcinogenic elements.
The aim of this study was to determine the effects of fiber feeding on short-chain fatty acid (SCFA) production in laboratory rats and in an in vitro fermentation model using fecal inocula from rats adapted to a high fiber diet. In addition, the effect of fiber intake on endogenous sterol synthesis was evaluated. Twenty male Sprague-Dawley rats were divided into four groups and fed a control or 30% fiber diet (cellulose, pectin or pea fiber) for 4 wk. In vitro fermentation was compared with measurements of cecal SCFA content of fiber-adapted rats. Sterol synthesis in isolated hepatocytes was determined in groups of five to seven rats fed 15% dietary fiber for 4 wk. Cellulose was poorly fermented in both the in vitro and in vivo experiments. Pectin fermentation produced high levels of propionate, whereas pea fiber was associated with notable butyrate production. Adaptation to pectin produced seven times more SCFA in rat cecal contents (515 +/- 78 mumol) in comparison to a fiber-free diet (70.6 +/- 4.9 mumol), with similar results observed in vitro. Sterol synthesis in hepatocytes of rats fed pectin was significantly greater than in those of control or cellulose-fed rats. Despite significantly higher rates of SCFA production in pectin-fed rats, cholesterol synthesis was not inhibited, suggesting that SCFA are not the cholesterol-lowering factor of highly fermentable fiber sources.
A mixed-grain, high-fiber cereal (Disivit) prepared from oats, corn, wheat and soybean was used to treat 20 patients with chronic constipation and 22 with hypercholesterolemia in double-blind, cross-over trials. Disivit (50 g/d, containing 12.5 g dietary fiber) was given to the constipated patients for 2 weeks and then a low-fiber placebo for another 2 weeks, and similarly for the hypercholesterolemic patients. In those with constipation, the frequency of bowel movements increased significantly, stools became softer and laxative intake decreased. In hypercholesterolemic patients serum cholesterol decreased significantly, but only by 15%. Thus the fiber cereal appears to be a suitable treatment for constipation, while for hypercholesterolemia a larger dose or a longer period of treatment may be required.
1. Bovine insulin dissolved in 0.05 M deoxycholic acid was absorbed through oral intubation in fish weighing 200-300 g. 2. The peak of absorption appeared in all fish, 30-45 min after intubation and was followed by a gradual decrease. The extent of absorption was extremely variable, with up to a 20-fold difference between individuals. No detectable insulin was found in fish intubated with vehicle. 3. The absorbed hormone retained 17-88% of its lipogenic bioactivity in vitro. The absorbed insulin lowered the levels of several amino acids in the intubated fish, indirectly indicating that its bioactivity was also retained in vivo.
Glucose metabolism was studied in ewes fed 800 g chopped alfalfa hay (H) or 400 g alfalfa hay and 400 g corn grain given in whole (HWC), ground (HGC) or extruded (HEC) form. Daily intake of metabolisable energy and crude protein were: 5.8 MJ, 109 g; 9.0 MJ, 84 g; 9.5 MJ, 84 g and 8.5 MJ, 88 g in H, HWC, HGC and HEC, respectively. In situ ruminal degradability ranked whole, ground, and extruded corn in ascending order. Ruminal pH and concentration of acetic acid were lower and of propionic acid higher (P less than 0.05) in HEC than in HGC and HWC groups. Plasma level of glucose (P less than 0.10), insulin (P less than 0.05), and the ratio of insulin to non-esterified fatty acids (NEFA) (P less than 0.01) were higher in HEC than in other groups. Glucose irreversible loss (GILR) and entry rate (GER), recycling (GRec) and reentry (GRee) were determined by double isotope dilution procedure. GER, but not GILR, was higher in HWC than in H and HGC (6.98 mg/min/kg BW0.75 vs 3.97 and 4.24 mg/min/kg BW0.75, respectively; P less than 0.05) and than in HEC (4.84 mg/min/kg BW0.75; P less than 0.10). GRec and GRee were higher in HWC than in the other treatments. Grinding or extruding the grain increased ruminal degradability and decreased glucose entry rate.
In an attempt to apply the concept of glycemic index (GI) and insulinemic index (II) to local eating habits, we examined the plasma glucose and insulin responses in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and healthy subjects to five mixed meals of different ethnic origins. All meals contained 50 g carbohydrate and were compared with a 50-g glucose load. The GI was highest for the Polish dish and lowest for the Syrian dish (66 +/- 5.5 vs 24 +/- 5.1). However, the II was the highest for the standard meal and lowest again for the Syrian dish (174 +/- 27 vs 66 +/- 25). A high correlation was found between the area under the glucose curve and the predicted GI in both NIDDM and healthy subjects. The GI concept is valid and potentially useful in diet planning and legume foods should be incorporated as a carbohydrate source when diets are being planned for NIDDM subjects or individuals with impaired glucose tolerance.
Methods of morphological, histochemical and immunohistochemical analyses were used to further characterize differences between tumourous and adjacent grossly normal tissues in chemically-induced colon cancer in rats. Colon tumors were induced by the treatment of rats with 1,2-dimethylhydrazine or with N-methyl-N'-nitro-N-nitrosoguanidine alone or with subsequent treatment with deoxycholic bile acid. Tissues were studied morphologically (for the presence of goblet cells in the colon crypts, and the extent of infiltration of lymphocytes into the crypts and between them), histochemically (for the presence of positive reaction to neutral and acid mucopolysaccharides) and immunohistochemically (for the presence of tissue polypeptide antigen). All data were evaluated quantitatively, and index of tissue damage was calculated for both tumorous and non-tumorous tissues. Significant morphological differences were found between tumorous and adjacent apparently normal tissue. Histochemically and immunohistochemically, both types of tissue reacted very similarly to exposure to the carcinogens. Index of damage was significantly different from normal untreated colon in both kinds of tissue. It was suggested that precancerous state in tissue adjacent-to-tumor could be detected using the combination of these methods.
The development of tumorigenic conditions in the carcinogen-exposed rat colon was studied using selected morphological, histochemical, immunohistochemical and biochemical methods of analysis. Rats were treated with two carcinogens: 1,2-dimethylhydrazine and N-methyl-N'-nitro-N-nitrosoguanidine alone or with deoxycholic acid as a tumor promoter. It was found that 3 months after treatment of animals with the carcinogens the following changes were developed in colonic tissue: infiltration of lymphocytes in the mucous membrane, high increase in mitotic index among epithelial cells, negative reactions of colonic cells for neutral mucopolysaccharides and sulfomucins and positive reactions to carboxyl groups, nonsulfated acid mucosubstances and tissue polypeptide antigens. An increase in the activity of ornithine decarboxylase in colonic tissue was developed within the same time period and has been seen only in those tissues which were characterized by the development of precancerous conditions. Individual variations were observed in the manifestation of the studied parameters in rat neoplastic colonic tissues. It is suggested that these differences reflect an individual sensitivity of animals to carcinogens and the magnitude of the dysplastic processes induced in the colon.
Insulin resistance is a predominant feature in women with polycystic ovarian syndrome (PCO). The cellular mechanisms for this insulin resistance have not been defined. In this study, major steps in the insulin action cascade, receptor binding, kinase activity, and glucose transport activity were evaluated in isolated adipocytes prepared from PCO subjects (n = 8) without acanthosis nigricans and in a group of age and weight-matched controls [normal cycling (NC) n = 8]. The PCO group was hyperinsulinemic and displayed elevated insulin responses to an iv glucose load. The binding of 125I-insulin to adipocytes was similar in cells from PCO and NC subjects. In PCO, autophosphorylation of the insulin receptor-subunit in the absence of insulin was normal but a significant decrease (30% below control) in maximal insulin stimulated autophosphorylation was observed. However, receptor kinase activity measured against the exogenous substrate poly glu:tyr (4:1) was normal. Cells from PCO subjects transported glucose at the same rate, in both the absence and presence of a maximal insulin concentration, as those from NC subjects. Strikingly, there was a large rightward shift in the insulin dose-response curve for transport stimulation in PCO cells (EC50 = 87 +/- 14 pmol in NC vs. 757 +/- 138 in PCO, P less than 0.0005); 8-fold greater insulin concentrations were required to attain comparable glucose transport rates in cells from PCO against NC. In conclusion, our results suggest that insulin resistance in PCO, as assessed in the adipocyte, is accompanied by normal function of insulin receptors, but involves a novel postreceptor defect in the insulin signal transduction chain between the receptor kinase and glucose transport.
Infusion of 17-beta-estradiol for 3 h caused a more than 100% increase in the number of PRL receptors (PRL) in the microsomal liver fraction of male rats without affecting the hormone-receptor affinity. A small but significant increase in PRL receptors also was found in testes but not kidneys. Testosterone infusion to female virgin rats for a similar time period resulted in some nonsignificant decreases in PRL receptors in the liver but not the mammary gland or kidneys. Testosterone infusion to males or 17-beta-estradiol infusion to females did not change the number or affinity of PRL and growth hormone receptors. The level of serum PRL was not influenced during infusion with both hormones.
Recombinant human growth hormone was administered orally to carp and serum levels of absorbed bioactive hormone were investigated using a highly sensitive Nb2 rat lymphoma cell bioassay and radioimmunoassay. Serum levels of bioactive hGH reached maximum values 30 min after oral intubation and then gradually decreased. Co-administration of the hormone with deoxycholate to fasted carp resulted in up to a 1000-fold increase in absorption compared to aqueous solutions of the hormone, but had no effect on the kinetics of the absorption process. Absorption of the hormone in starved fish was significantly greater than in fed fish. A linear dose-response relationship was observed for hGH in starved fish and the level of absorption in fed fish was influenced by the time interval from the last meal. The ratio of bioactive to immunoactive hGH in fasted fish indicated little loss of bioactivity and also that deoxycholate may be protective against hGH degradation. The present study demonstrates for the first time that biologically active hGH is absorbed in the common carp after oral intubation. Furthermore, the use of a biological detergent dramatically increased the extent of hGH absorption. Additional studies are required to establish the appropriate conditions (diet composition, feeding level, and frequency, etc.) in which polypeptide hormones could be introduced orally to fish.
Glycogen synthase (GS) activity was characterized in rat brown adipose tissue (BAT) and the activity was found to be much higher than that in white adipose tissue. Prolonged starvation had no effect on the active form of GS, as found in the liver and muscle. The GS activity was similar in BAT of rats housed in an animal room (21 +/- 1 degree) whether they were fed on high-carbohydrate, high-fat, or stock diets. Acclimatization of rats to cold (4 +/- 1 degree) for 2 weeks significantly increased GS activity. This increase in the cold was fivefold greater when rats were fed on high-carbohydrate diets than in control rats at room temperature fed on an identical diet. The increase was accompanied by a large accumulation of glycogen in BAT. It was concluded that GS may play an important role in BAT and may contribute to the control of blood glucose in a cold environment. Its relevance to thermogenesis requires further elucidation.