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Sample records for intestinal glucose absorption

  1. Hydroxycitric acid delays intestinal glucose absorption in rats.

    PubMed

    Wielinga, Peter Y; Wachters-Hagedoorn, Renate E; Bouter, Brenda; van Dijk, Theo H; Stellaard, Frans; Nieuwenhuizen, Arie G; Verkade, Henkjan J; Scheurink, Anton J W

    2005-06-01

    In this study, we investigated in rats if hydroxycitric acid (HCA) reduces the postprandial glucose response by affecting gastric emptying or intestinal glucose absorption. We compared the effect of regulator HCA (310 mg/kg) and vehicle (control) on the glucose response after an intragastric or intraduodenal glucose load to investigate the role of altered gastric emptying. Steele's one-compartment model was used to investigate the effect of HCA on systemic glucose appearance after an intraduodenal glucose load, using [U-(13)C]-labeled glucose and d-[6,6-(2)H(2)]-labeled glucose. Because an effect on postabsorptive glucose clearance could not be excluded, the effect of HCA on the appearance of enterally administered glucose in small intestinal tissue, liver, and portal and systemic circulation was determined by [U-(14)C]glucose infusion. Data show that HCA treatment delays the intestinal absorption of enterally administered glucose at the level of the small intestinal mucosa in rats. HCA strongly attenuated postprandial blood glucose levels after both intragastric (P < 0.01) and intraduodenal (P < 0.001) glucose administration, excluding a major effect of HCA on gastric emptying. HCA delayed the systemic appearance of exogenous glucose but did not affect the total fraction of glucose absorbed over the study period of 150 min. HCA treatment decreased concentrations of [U-(14)C]glucose in small intestinal tissue at 15 min after [U-(14)C]glucose administration (P < 0.05), in accordance with the concept that HCA delays the enteral absorption of glucose. These data support a possible role for HCA as food supplement in lowering postprandial glucose profiles. PMID:15604199

  2. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    SciTech Connect

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  3. Regulation of Intestinal Glucose Absorption by Ion Channels and Transporters.

    PubMed

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-14

    The absorption of glucose is electrogenic in the small intestinal epithelium. The major route for the transport of dietary glucose from intestinal lumen into enterocytes is the Na⁺/glucose cotransporter (SGLT1), although glucose transporter type 2 (GLUT2) may also play a role. The membrane potential of small intestinal epithelial cells (IEC) is important to regulate the activity of SGLT1. The maintenance of membrane potential mainly depends on the activities of cation channels and transporters. While the importance of SGLT1 in glucose absorption has been systemically studied in detail, little is currently known about the regulation of SGLT1 activity by cation channels and transporters. A growing line of evidence suggests that cytosolic calcium ([Ca(2+)]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca(2+) in IEC are regulated by cation channels and transporters, such as Ca(2+) channels, K⁺ channels, Na⁺/Ca(2+) exchangers, and Na⁺/H⁺ exchangers. In this review, we consider the involvement of these cation channels and transporters in the regulation of glucose uptake in the small intestine. Modulation of them may be a potential strategy for the management of obesity and diabetes.

  4. Proximal small intestinal mucosal injury. Maintenance of glucose and glucose polymer absorption, attenuation of disaccharide absorption.

    PubMed

    Palacios, M; Madariaga, H; Heitlinger, L; Lee, P C; Lebenthal, E

    1989-03-01

    The effect of chronic intragastric infusion of hypertonic mannitol on small intestinal mucosal structure and function was studied in adult rats. Animals were gavage-fed 20% mannitol (1300 mosm) at a dose of 5 ml/100 g body weight daily for seven days. Control animals were gavage-fed tap water on the same schedule. On day 8, the animals were anesthetized, the duodenum cannulated, and a test sugar (glucose, glucose polymer, lactose, sucrose, or maltose) was infused at a dose of 0.5 g/kg body weight in 2.5 ml distilled water over less than 1 min. Portal vein glucose was measured at 30-min intervals from 0 to 120 min. Mannitol treatment resulted in histologic and biochemical alterations (reduced lactase, sucrase, maltase) limited to the proximal small intestine compared to the control group. The absorption of glucose and glucose polymers was similar in mannitol-treated and control animals. In contrast, digestion and absorption of lactose, sucrose, and maltose was significantly diminished in mannitol-treated animals when compared to controls. No changes in permeability to polyethylene glycol 4000 or Na+-coupled glucose transport were observed in mannitol-treated animals compared to controls. These data suggest that when the intestinal mucosa is exposed to hyperosmolar loads that the digestive capacity for disaccharides is suppressed more than its glucose absorptive capacities. Furthermore, glucose oligomers may be more readily digested and absorbed than disaccharides, in this setting, due, in part, to the proximal injury and less pronounced proximal-distal gradient for glucoamylase than other brush-border carbohydrases.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    PubMed

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

  6. Hummingbirds rely on both paracellular and carrier-mediated intestinal glucose absorption to fuel high metabolism.

    PubMed

    McWhorter, Todd J; Bakken, Bradley Hartman; Karasov, William H; del Rio, Carlos Martínez

    2006-03-22

    Twenty years ago, the highest active glucose transport rate and lowest passive glucose permeability in vertebrates were reported in Rufous and Anna's hummingbirds (Selasphorus rufus, Calypte anna). These first measurements of intestinal nutrient absorption in nectarivores provided an unprecedented physiological foundation for understanding their foraging ecology. They showed that physiological processes are determinants of feeding behaviour. The conclusion that active, mediated transport accounts for essentially all glucose absorption in hummingbirds influenced two decades of subsequent research on the digestive physiology and nutritional ecology of nectarivores. Here, we report new findings demonstrating that the passive permeability of hummingbird intestines to glucose is much higher than previously reported, suggesting that not all sugar uptake is mediated. Even while possessing the highest active glucose transport rates measured in vertebrates, hummingbirds must rely partially on passive non-mediated intestinal nutrient absorption to meet their high mass-specific metabolic demands.

  7. [Glucose absorption in the rat small intestine in vivo after various levels of local substrate load].

    PubMed

    Gruzdkov, A A; Gromova, L V

    2013-05-01

    In order to evaluate relative roles of various mechanisms of glucose transport in the small intestine at high substrate loads in chronic experiments on rats, we investigated kinetics of glucose absorption in isolated part (-20 cm) of the intestine after its perfusion for 6 and 14 days during 1.5 h per day with 125 mM glucose solution (gr. 1--increased substrate load) or during 45-60 min per day with 25 mM glucose solution (gr. 2--reduced substrate load). The results of the experiments were analyzed by means of mathematical simulation. It was found that in the rats of gr. 1 the regular substrate load was more effective in maintaining a high level of glucose absorption in the isolated part of the intestine. Adaptation of glucose absorption to the increased local glucose load occurs due to enhancement of the secondary active transport via SGLT1. This component in many times exceeds the "unsaturated" component of glucose absorption, which is mainly determined by the facilitated diffusion via GLUT2, both at high and low glucose concentrations in the intestinal lumen.

  8. [Circadian rhythm of intestinal glucose absorption in fasting and fed rats].

    PubMed

    Voloshenovich, M I; Labusheva, M A; Ugolev, A M; Pishak, V P

    1993-01-01

    Under conditions of chronic experiment the circadian cycle of glucose transport was determined. An isolated proximal area of the small intestine was perfused by glucose, fructose, medical bile and Ringer's solutions in various intervals of the 24 hour period. The circadian cycle of glucose absorption is disturbed in the fasting rats. Various substrates differently alter their amplitude and acro-phase of absorption. Ringer's solution perfusion shifts the acro-phase absorption to evening time, while that of fructose occurs during day time and that of bile takes place at night. The circadian cycle of the fed rats is less subject to shifts. Fasting is a powerful exogenous factor causing structural changes in the small intestine and altering the circadian cycle of glucose absorption.

  9. A diurnal rhythm in the absorption of glucose and water by isolated rat small intestine.

    PubMed

    Fisher, R B; Gardner, M L

    1976-01-01

    1. Glucose and water absorption by isolated small intestine from rats which have had unrestricted access to food is 50-60% higher at night than during the daytime. 2. When the feeding time is restricted to 06.00-09.00 hr G.M.T. glucose and water absorption rates in the period from 3 to 7 hr after withdrawal of food are almost as high as the rates observed at night-time in the animals with unrestricted feeding. 3. These changes in absorption rates appear to be associated with feeding time and not with the pattern of illumination.

  10. Diet effects on glucose absorption in the small intestine of neonatal calves: importance of intestinal mucosal growth, lactase activity, and glucose transporters.

    PubMed

    Steinhoff-Wagner, Julia; Zitnan, Rudolf; Schönhusen, Ulrike; Pfannkuche, Helga; Hudakova, Monika; Metges, Cornelia C; Hammon, Harald M

    2014-10-01

    Colostrum (C) feeding in neonatal calves improves glucose status and stimulates intestinal absorptive capacity, leading to greater glucose absorption when compared with milk-based formula feeding. In this study, diet effects on gut growth, lactase activity, and glucose transporters were investigated in several gut segments of the small intestine. Fourteen male German Holstein calves received either C of milkings 1, 3, and 5 (d 1, 2, and 3 in milk) or respective formulas (F) twice daily from d 1 to d 3 after birth. Nutrient content, and especially lactose content, of C and respective F were the same. On d 4, calves were fed C of milking 5 or respective F and calves were slaughtered 2h after feeding. Tissue samples from duodenum and proximal, mid-, and distal jejunum were taken to measure villus size and crypt depth, mucosa and brush border membrane vesicles (BBMV) were taken to determine protein content, and mRNA expression and activity of lactase and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter (GLUT2) were determined from mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and BBMV were determined, as well as immunochemically localized GLUT2 in the intestinal mucosa. Villus circumference, area, and height were greater, whereas crypt depth was smaller in C than in F. Lactase activity tended to be greater in C than in F. Protein expression of SGLT1 was greater in F than in C. Parameters of villus size, lactase activity, SGLT1 protein expression, as well as apical and basolateral GLUT2 localization in the enterocytes differed among gut segments. In conclusion, C feeding, when compared with F feeding, enhances glucose absorption in neonatal calves primarily by stimulating mucosal growth and increasing absorptive capacity in the small intestine, but not by stimulating abundance of intestinal glucose transporters.

  11. Multifaceted interplay among mediators and regulators of intestinal glucose absorption: potential impacts on diabetes research and treatment.

    PubMed

    Chan, Leo Ka Yu; Leung, Po Sing

    2015-12-01

    Glucose is the prominent molecule that characterizes diabetes and, like the vast majority of nutrients in our diet, it is absorbed and enters the bloodstream directly through the small intestine; hence, small intestine physiology impacts blood glucose levels directly. Accordingly, intestinal regulatory modulators represent a promising avenue through which diabetic blood glucose levels might be moderated clinically. Despite the critical role of small intestine in blood glucose homeostasis, most physiological diabetes research has focused on other organs, such as the pancreas, kidney, and liver. We contend that an improved understanding of intestinal regulatory mediators may be fundamental for the development of first-line preventive and therapeutic interventions in patients with diabetes and diabetes-related diseases. This review summarizes the major important intestinal regulatory mediators, discusses how they influence intestinal glucose absorption, and suggests possible candidates for future diabetes research and the development of antidiabetic therapeutic agents.

  12. Non-starch polysaccharides extracted from seaweed can modulate intestinal absorption of glucose and insulin response in the pig.

    PubMed

    Vaugelade, P; Hoebler, C; Bernard, F; Guillon, F; Lahaye, M; Duee, P H; Darcy-Vrillon, B

    2000-01-01

    We have investigated the possible effects of algal polysaccharides on postprandial blood glucose and insulin responses in an animal model, the pig. Three seaweed fibres of different viscosities, extracted from Palmaria palmata (PP), Eucheuma cottonii (EC), or Laminaria digitata (LD), were compared to purified cellulose (CEL). Blood glucose and plasma insulin levels were monitored and intestinal absorption quantified for 8 h following a high carbohydrate test-meal supplemented with 5% fibre. Digestive contents were also sampled, 5 h postprandial. As compared to CEL, PP had no effect on glucose and insulin responses. The latter decreased with EC, but glucose absorption balance was not modified. LD addition resulted in a dramatically reduced glucose absorption balance, accompanied by a higher amount of starch left in the small intestine. Among polysaccharides tested, only the highly viscous alginates could affect intestinal absorption of glucose and insulin response. PMID:10737549

  13. Effect of cadmium and chromium on the intestinal absorption of glucose in the snakehead fish, Channa punctatus.

    PubMed

    Sastry, K V; Sunita, K

    1982-02-01

    The effect of five concentrations of cadmium and chromium (10 mM, 1 mM, 0.1 mM, 0.01 mM and 0.001 mM) on the rate of absorption of glucose from the intestine of te snakehead fish, channa punctatus, was studied at 23 degrees C. All concentrations of cadmium decreased the rate of glucose transport. Maximum decrease was recorded with 10 mM of cadmium. The rate of transport decreased with an increase in the concentration of cadmium used. Chromium increased glucose absorption rate at all concentrations examined; the highest rate of absorption occurred at 0.001 mM of chromium.

  14. Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1.

    PubMed

    Ducroc, Robert; Guilmeau, Sandra; Akasbi, Khalil; Devaud, Hélène; Buyse, Marion; Bado, André

    2005-02-01

    The effect of leptin on glucose transport was studied in rat jejunal mucosa in Ussing chambers. Leptin was added in the luminal or the serosal compartment before the tissues were challenged with 1, 10, or 50 mmol/l glucose. In response to 10 mmol/l glucose, the increase in short-circuit current (DeltaIsc) reached 26.8 +/- 2.1 microA/cm(2). Luminal addition of leptin dramatically decreased glucose-induced Isc (90.5% for 10 nmol/l leptin). Inhibition was maximal after 5 min and dose dependent (IC(50) = 0.13 nM). Western blot analysis showed that rapid inhibition of glucose-induced Isc by leptin was associated with a parallel decrease in the abundance of sodium-glucose transporter-1 in brush border membranes. Inhibition by luminal leptin of DeltaIsc was prevented by inhibitor of conventional protein kinase C isoforms. Serosal addition of leptin did not decrease glucose-induced Isc within 5 min and reached maximum after 10 min. The effect of leptin from serosal side was blocked by cholecystokinin (CCK) receptor-2 receptor antagonist YM022. Altogether, these data demonstrate that luminal leptin induces rapid inhibition of glucose entry into enterocyte. The slower action of leptin on the serosal side of mucosa seems indirect and is likely mediated by endogenous CCK. They demonstrate that gut leptin is a major regulator of rapid intestinal glucose transport.

  15. Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption.

    PubMed

    Moran, A W; Al-Rammahi, M; Zhang, C; Bravo, D; Calsamiglia, S; Shirazi-Beechey, S P

    2014-01-01

    Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep

  16. Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption.

    PubMed

    Moran, A W; Al-Rammahi, M; Zhang, C; Bravo, D; Calsamiglia, S; Shirazi-Beechey, S P

    2014-01-01

    Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregulation in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na(+)-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep

  17. [FREE CONSUMPTION OF GLUCOSE SOLUTION BY RATS AS A CRITERION FOR EVALUATION ITS ABSORPTION IN THE SMALL INTESTINE (Experimental study and mathematical modeling)].

    PubMed

    Gruzdkov, A A; Gromova, L V; Dmitrieva, Yu V; Alekseeva, A S

    2015-06-01

    The aim of the work is to analyze the relationship between consumption of glucose solution by rats and its absorption, and to use this fact for assessment of the absorptive capacity of the small intestine in non anesthetized animals in vivo. Consumption of glucose solution (200 g/l) by fasted rats was recorded in the control, and after administration of phloridzin--inhibitor of glucose active transport- or 3 hours after the restriction stress. On the mathematical model we studied the relative role of factors that can influence the temporal dynamics of glucose consumption by rats. The rate of glucose consumption was observed being decreased in the presence of phloridzin (1 mM), and be increased after the stress. The results of modeling are consistent with the experimental data and show that the rate of consumption of glucose solutions considerably more depends on the transport activity of the small intestine than on glucose concentration in the solution, or on the substrate regulation of the stomach emptying. Analysis of dynamics of consumption of glucose solution by intact rats may be considered as one of promising approaches to assessing the absorptive capacity of the small intestine under natural conditions.

  18. Effect of Walker 256 tumor growth on intestinal absorption of leucine, methionine and glucose in newly weaned and mature rats.

    PubMed

    Gomes-Marcondes, M C; Honma, H N; Areas, M A; Cury, L

    1998-10-01

    In tumor-bearing rats, most of the serum amino acids are used for synthesis and oxidation processes by the neoplastic tissue. In the present study, the effect of Walker 256 carcinoma growth on the intestinal absorption of leucine, methionine and glucose was investigated in newly weaned and mature rats. Food intake and carcass weight were decreased in newly weaned (NT) and mature (MT) rats bearing Walker 256 tumor in comparison with control animals (NC and MC). The tumor/carcass weight ratio was higher in NT than in MT rats, whereas nitrogen balance was significantly decreased in both as compared to control animals. Glucose absorption was significantly reduced in MT rats (MT = 47.3 +/- 4.9 vs MC = 99.8 +/- 5.3 nmol min-1 cm-1, Kruskal-Wallis test, P < 0.05) but this fact did not hamper the evolution of cancer. There was a significant increase in methionine absorption in both groups (NT = 4.2 +/- 0.3 and MT = 2.0 +/- 0.1 vs NC = 3.7 +/- 0.1 and MC = 1.2 +/- 0.2 nmol min-1 cm-1, Kruskal-Wallis test, P < 0.05), whereas leucine absorption was increased only in young tumor-bearing rats (NT = 8.6 +/- 0.2 vs NC = 7.7 +/- 0.4 nmol min-1 cm-1, Kruskal-Wallis test, P < 0.05), suggesting that these metabolites are being used for synthesis and oxidation processes by the neoplastic cells, which might ensure their rapid proliferation especially in NT rats.

  19. Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose

    SciTech Connect

    Donatucci, D.A.; Liener, I.E.; Gross, C.J.

    1987-12-01

    The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of /sup 125/I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of (/sup 14/C)glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of their counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans.

  20. Neural regulation of intestinal nutrient absorption.

    PubMed

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

    The nervous system and the gastrointestinal (GI) tract share several common features including reciprocal interconnections and several neurotransmitters and peptides known as gut peptides, neuropeptides or hormones. The processes of digestion, secretion of digestive enzymes and then absorption are regulated by the neuro-endocrine system. Luminal glucose enhances its own absorption through a neuronal reflex that involves capsaicin sensitive primary afferent (CSPA) fibres. Absorbed glucose stimulates insulin release that activates hepatoenteric neural pathways leading to an increase in the expression of glucose transporters. Adrenergic innervation increases glucose absorption through α1 and β receptors and decreases absorption through activation of α2 receptors. The vagus nerve plays an important role in the regulation of diurnal variation in transporter expression and in anticipation to food intake. Vagal CSPAs exert tonic inhibitory effects on amino acid absorption. It also plays an important role in the mediation of the inhibitory effect of intestinal amino acids on their own absorption at the level of proximal or distal segment. However, chronic extrinsic denervation leads to a decrease in intestinal amino acid absorption. Conversely, adrenergic agonists as well as activation of CSPA fibres enhance peptides uptake through the peptide transporter PEPT1. Finally, intestinal innervation plays a minimal role in the absorption of fat digestion products. Intestinal absorption of nutrients is a basic vital mechanism that depends essentially on the function of intestinal mucosa. However, intrinsic and extrinsic neural mechanisms that rely on several redundant loops are involved in immediate and long-term control of the outcome of intestinal function.

  1. Incomplete intestinal absorption of fructose.

    PubMed

    Kneepkens, C M; Vonk, R J; Fernandes, J

    1984-08-01

    Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children.

  2. Incomplete intestinal absorption of fructose.

    PubMed Central

    Kneepkens, C M; Vonk, R J; Fernandes, J

    1984-01-01

    Intestinal D-fructose absorption in 31 children was investigated using measurements of breath hydrogen. Twenty five children had no abdominal symptoms and six had functional bowel disorders. After ingestion of fructose (2 g/kg bodyweight), 22 children (71%) showed a breath hydrogen increase of more than 10 ppm over basal values, indicating incomplete absorption: the increase averaged 53 ppm, range 12 to 250 ppm. Four of these children experienced abdominal symptoms. Three of the six children with bowel disorders showed incomplete absorption. Seven children were tested again with an equal amount of glucose, and in three of them also of galactose, added to the fructose. The mean maximum breath hydrogen increases were 5 and 10 ppm, respectively, compared with 103 ppm after fructose alone. In one boy several tests were performed with various sugars; fructose was the only sugar incompletely absorbed, and the effect of glucose on fructose absorption was shown to be dependent on the amount added. It is concluded that children have a limited absorptive capacity for fructose. We speculate that the enhancing effect of glucose and galactose on fructose absorption may be due to activation of the fructose carrier. Apple juice in particular contains fructose in excess of glucose and could lead to abdominal symptoms in susceptible children. PMID:6476870

  3. Luminal glucose does not enhance active intestinal calcium absorption in mice: evidence against a role for Ca(v)1.3 as a mediator of calcium uptake during absorption.

    PubMed

    Reyes-Fernandez, Perla C; Fleet, James C

    2015-11-01

    Intestinal Ca absorption occurs through a 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels after a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine-week-old male C57BL/6 J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week, and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), calbindin D9k (CaBPD9k), and Cav1.3 messenger RNA (mRNA) levels were measured in the duodenum, jejunum, and ileum. TRPV6 and CaBPD9k expressions were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs, whereas Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low-Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (P = .003), serum 1,25(OH)2D3 (P < .001), and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (P = .6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo.

  4. Polyamines alter intestinal glucose transport.

    PubMed

    Johnson, L R; Brockway, P D; Madsen, K; Hardin, J A; Gall, D G

    1995-03-01

    Polyamines are required for the growth of all eukaryotic cells. Enterocytes respond to luminal nutrients with large increases in polyamine synthesis, even though they are mature, nonproliferating cells. The role of polyamines in these cells is unknown. The current experiments examined whether polyamines affected intestinal transport of glucose, since absorption is the primary activity of enterocytes and since polyamines are known to affect membrane function and stability. Glucose transport was examined in rabbit brush-border membrane vesicles (BBMV). BBMV from rabbits given 5% alpha-difluoromethylornithine (DFMO) in their drinking water 24 h before they were killed transported significantly less glucose than control vesicles [38% decrease in maximal transport rate (Jmax)]. Orogastric administration of spermine, spermidine, or putrescine to DFMO-treated animals 24 h before they were killed prevented the decrease. In rabbits receiving only orogastric spermine, glucose transport was significantly increased (64% increase in Jmax), whereas in vivo spermidine and putrescine decreased Jmax. This increase in Jmax caused by in vivo administration of spermine was not dependent on protein synthesis. Addition of polyamines whether in vivo or in vitro decreased Michaelis constant in vesicles from control and DFMO-treated animals. The change in glucose transport induced by DFMO or polyamines was not related to altered membrane lipid composition or fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Inhibition of food intake in the rat following complete absorption of glucose delivered into the stomach, intestine or liver.

    PubMed Central

    Booth, D A; Jarman, S P

    1976-01-01

    1. Solutions of glucose or other carbohydrates were administered during the dark or light period of the circadian cycle to rats which had been only briefly deprived of food. 2. food was restored to the animals at various times after administration of a glucose load by stomach tube. With delays between loading and access to food of up to 3 hr by night and 2 hr by day, subsequent food intake was less than intake after non-nutritive loads. 3. measurement of the glucose content of the gastrointestinal tract at various times after glucose loading showed that this depression of intake was still apparent even when the rat was offered food some time after complete absorption of the stomach load. 4. infusion of a glucose solution into the duodenum or the hepatic protal vein also inhibited subsequent food intake. 5. in all cases, the inhibition of food intake was expressed as a decrease in the size of the first meal after restoring access to food. 6. these results provide the first demonstration that the entry of normal amounts of carbohydrate into the body by the physiological route is followed by depression of food intake which lasts until after absorption is complete. PMID:957255

  6. Inhibition of food intake in the rat following complete absorption of glucose delivered into the stomach, intestine or liver.

    PubMed

    Booth, D A; Jarman, S P

    1976-07-01

    1. Solutions of glucose or other carbohydrates were administered during the dark or light period of the circadian cycle to rats which had been only briefly deprived of food. 2. food was restored to the animals at various times after administration of a glucose load by stomach tube. With delays between loading and access to food of up to 3 hr by night and 2 hr by day, subsequent food intake was less than intake after non-nutritive loads. 3. measurement of the glucose content of the gastrointestinal tract at various times after glucose loading showed that this depression of intake was still apparent even when the rat was offered food some time after complete absorption of the stomach load. 4. infusion of a glucose solution into the duodenum or the hepatic protal vein also inhibited subsequent food intake. 5. in all cases, the inhibition of food intake was expressed as a decrease in the size of the first meal after restoring access to food. 6. these results provide the first demonstration that the entry of normal amounts of carbohydrate into the body by the physiological route is followed by depression of food intake which lasts until after absorption is complete.

  7. Intestinal Folate Absorption

    PubMed Central

    Olinger, Edward J.; Bertino, Joseph R.; Binder, Henry J.

    1973-01-01

    These studies were designed to determine whether pteroylmonoglutamic acid (PGA) at physiologic concentrations is transported across the small intestine unaltered or is reduced and methylated to the circulating folate form (5-methyltetrahydrofolate [5-MeFH4]) during absorption. [3H]PGA was incubated in vitro on the mucosal side of rat jejunum. Of the folate transferred to the serosal side, the percent identified as 5-MeFH4 by DEAE-Sephadex chromtography was inversely related to the initial mucosa PGA concentration: at 7, 20, and 2,000 nM, 44%, 34%, and 2%, respectively, was converted to 5-MeFH4. In contrast, less than 4% of the folate transferred across ileal mucosa was 5-MeFH4 when the initial mucosa concentration was 20 nM. Specific activity of dihydrofolate (DHF) reductase, the enzyme responsible for converting PGA to tetrahydrofolic acid, was measured in villus homogenates and was significantly greater in the jejunum than in the ileum. 1,000 nM methotrexate (MTX), a DHF reductase inhibitor, markedly inhibited PGA conversion to 5-MeFH4 by the jejunum. Studies of transmural flux, initial rate of mucosal entry (influx) and mucosal accumulation (uptake) of folate were also performed. Although MTX did not alter the influx of PGA, MTX decreased jejunal mucosal uptake but increased transmural movement. Transmural folate movement across ileal mucosa was greater than across jejunal mucosa although mucosal uptake was greater in the jejunum than in the ileum. These results could explain previous studies which have failed to identify conversion of PGA to 5-MeFH4 when intestinal preparations have been exposed to higher and less physiologic concentrations of PGA. Further, these studies suggest that 5-MeFH4 may be retained by the jejunal mucosa. PMID:4727453

  8. Intestinal absorption of berberine and 8-hydroxy dihydroberberine and their effects on sugar absorption in rat small intestine.

    PubMed

    Wei, Shi-chao; Dong, Su; Xu, Li-jun; Zhang, Chen-yu

    2014-04-01

    The intestinal absorption of berberine (Ber) and its structural modified compound 8-hydroxy dihydroberberine (Hdber) was compared, and their effects on the intestinal absorption of sugar by perfusion experiment were investigated in order to reveal the mechanism of low dose and high activity of Hdber in the treatment of hyperglycemia. The absorption of Hdber and Ber in rat small intestine was measured by in situ perfusion. High performance liquid chromatography (HPLC) was used to determine the concentrations of Hdber and Ber. In situ perfusion method was also used to study the effects of Hdber and Ber on sugar intestinal absorption. Glucose oxidase method and UV spectrophotometry were applied to examine the concentrations of glucose and sucrose in the perfusion fluid. The results showed that the absorption rate of Ber in the small intestine was lower than 10%, but that of Hdber was larger than 70%. Both Hdber and Ber inhibited the absorption of glucose and sucrose at the doses of 10 and 20 μg/mL. However, Hdber presented stronger activity than Ber (P<0.01). It is suggested that Hdber is absorbed easily in rat small intestine and that its inhibitory effect on the absorption of sugar is better than Ber.

  9. Fat-soluble vitamin intestinal absorption: absorption sites in the intestine and interactions for absorption.

    PubMed

    Goncalves, Aurélie; Roi, Stéphanie; Nowicki, Marion; Dhaussy, Amélie; Huertas, Alain; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2015-04-01

    The interactions occurring at the intestinal level between the fat-soluble vitamins A, D, E and K (FSVs) are poorly documented. We first determined each FSV absorption profile along the duodenal-colonic axis of mouse intestine to clarify their respective absorption sites. We then investigated the interactions between FSVs during their uptake by Caco-2 cells. Our data show that vitamin A was mostly absorbed in the mouse proximal intestine, while vitamin D was absorbed in the median intestine, and vitamin E and K in the distal intestine. Significant competitive interactions for uptake were then elucidated among vitamin D, E and K, supporting the hypothesis of common absorption pathways. Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E. These results should be taken into account, especially for supplement formulation, to optimise FSV absorption.

  10. Inhibition of Intestinal α-Glucosidase and Glucose Absorption by Feruloylated Arabinoxylan Mono- and Oligosaccharides from Corn Bran and Wheat Aleurone

    PubMed Central

    Malunga, Lovemore Nkhata; Eck, Peter; Beta, Trust

    2016-01-01

    The effect of feruloylated arabinoxylan mono- and oligosaccharides (FAXmo) on mammalian α-glucosidase and glucose transporters was investigated using human Caco-2 cells, rat intestinal acetone powder, and Xenopus laevis oocytes. The isolated FAXmo from wheat aleurone and corn bran were identified to have degree of polymerization (DP) of 4 and 1, respectively, by HPLC-MS. Both FAXmo extracts were effective inhibitors of sucrase and maltase functions of the α-glucosidase. The IC50 for FAXmo extracts on Caco-2 cells and rat intestinal α-glucosidase was 1.03–1.65 mg/mL and 2.6–6.5 mg/mL, respectively. Similarly, glucose uptake in Caco-2 cells was inhibited up to 40%. The inhibitory effect of FAXmo was dependent on their ferulic acid (FA) content (R = 0.95). Sodium independent glucose transporter 2 (GLUT2) activity was completely inhibited by FAXmo in oocytes injected to express GLUT2. Our results suggest that ferulic acid and feruloylated arabinoxylan mono-/oligosaccharides have potential for use in diabetes management. PMID:27073693

  11. Inhibition of Intestinal α-Glucosidase and Glucose Absorption by Feruloylated Arabinoxylan Mono- and Oligosaccharides from Corn Bran and Wheat Aleurone.

    PubMed

    Malunga, Lovemore Nkhata; Eck, Peter; Beta, Trust

    2016-01-01

    The effect of feruloylated arabinoxylan mono- and oligosaccharides (FAXmo) on mammalian α-glucosidase and glucose transporters was investigated using human Caco-2 cells, rat intestinal acetone powder, and Xenopus laevis oocytes. The isolated FAXmo from wheat aleurone and corn bran were identified to have degree of polymerization (DP) of 4 and 1, respectively, by HPLC-MS. Both FAXmo extracts were effective inhibitors of sucrase and maltase functions of the α-glucosidase. The IC50 for FAXmo extracts on Caco-2 cells and rat intestinal α-glucosidase was 1.03-1.65 mg/mL and 2.6-6.5 mg/mL, respectively. Similarly, glucose uptake in Caco-2 cells was inhibited up to 40%. The inhibitory effect of FAXmo was dependent on their ferulic acid (FA) content (R = 0.95). Sodium independent glucose transporter 2 (GLUT2) activity was completely inhibited by FAXmo in oocytes injected to express GLUT2. Our results suggest that ferulic acid and feruloylated arabinoxylan mono-/oligosaccharides have potential for use in diabetes management.

  12. The sweet life: diet sugar concentration influences paracellular glucose absorption.

    PubMed

    Napier, Kathryn R; Purchase, Cromwell; McWhorter, Todd J; Nicolson, Susan W; Fleming, Patricia A

    2008-10-23

    Small birds and bats face strong selection pressure to digest food rapidly in order to reduce digesta mass carried during flight. One mechanism is rapid absorption of a high proportion of glucose via the paracellular pathway (transfer between epithelial cells, not mediated by transporter proteins). Intestinal paracellular permeability to glucose was assessed for two nectarivorous passerines, the Australian New Holland honeyeater (Phylidonyris novaehollandiae) and African white-bellied sunbird (Cinnyris talatala) by measuring the bioavailability of radiolabelled, passively absorbed L-glucose. Bioavailability was high in both species and increased with diet sugar concentration (honeyeaters, 37 and 81% and sunbirds, 53 and 71% for 250 and 1,000 mmoll-1 sucrose diets, respectively). We conclude that the relative contribution of paracellular to total glucose absorption increases with greater digesta retention time in the intestine, and paracellular absorption may also be modulated by factors such as intestinal lumen osmolality and interaction with mediated glucose uptake. The dynamic state of paracellular absorption should be taken into account in future studies. PMID:18559309

  13. The sweet life: diet sugar concentration influences paracellular glucose absorption.

    PubMed

    Napier, Kathryn R; Purchase, Cromwell; McWhorter, Todd J; Nicolson, Susan W; Fleming, Patricia A

    2008-10-23

    Small birds and bats face strong selection pressure to digest food rapidly in order to reduce digesta mass carried during flight. One mechanism is rapid absorption of a high proportion of glucose via the paracellular pathway (transfer between epithelial cells, not mediated by transporter proteins). Intestinal paracellular permeability to glucose was assessed for two nectarivorous passerines, the Australian New Holland honeyeater (Phylidonyris novaehollandiae) and African white-bellied sunbird (Cinnyris talatala) by measuring the bioavailability of radiolabelled, passively absorbed L-glucose. Bioavailability was high in both species and increased with diet sugar concentration (honeyeaters, 37 and 81% and sunbirds, 53 and 71% for 250 and 1,000 mmoll-1 sucrose diets, respectively). We conclude that the relative contribution of paracellular to total glucose absorption increases with greater digesta retention time in the intestine, and paracellular absorption may also be modulated by factors such as intestinal lumen osmolality and interaction with mediated glucose uptake. The dynamic state of paracellular absorption should be taken into account in future studies.

  14. Dietary inulin alters the intestinal absorptive and barrier function of piglet intestine after weaning.

    PubMed

    Awad, Wageha A; Ghareeb, Khaled; Paßlack, Nadine; Zentek, Jürgen

    2013-08-01

    An experiment was conducted to study the effects of dietary inulin supplementation on the electrophysiological properties of small intestine of suckling and weaned piglets as indicators for glucose absorption and barrier function. Ten sows were divided into two groups, receiving either a control diet, or a diet with 3% inulin. The diets were fed from 3 weeks ante partum to 6 weeks post partum. In the first 2 weeks of life, piglets received only sow's milk. Irrespective to sex and without castration of males, four piglets (one piglet of each litter) from each group were selected and sacrificed on day 10 of age. The gastrointestinal tract of each piglet was removed and segments were immediately taken from the mid-jejunum and mounted in Ussing chambers. Furthermore, at weaning (6 weeks old) 8 piglets were randomly selected irrespective to sex and males were un-castrated (4 animals from sows received control diet and 4 animals from sows received 3% inulin supplemented diet) and fed for 2 weeks either control weaning diet or inulin supplemented diet. Thereafter segments of the mid-jejunum were used to investigate the effect of inulin on the gut electrophysiology of weaned piglets. The increase in short-circuit current (Isc) after the addition of glucose is an indicator of higher glucose absorption and the higher tissue conductance (Gt) of the epithelium suggested a higher intestinal permeability to paracellular Na(+). In suckling piglets, the addition of d-glucose on the luminal side of the isolated jejunal mucosa increased (P<0.001) the Isc in the inulin-supplemented and control groups compared to basal values. Electrogenic glucose transport (ΔIsc) was similar in suckling piglets from sows fed inulin or control diet, suggesting that feeding of inulin to the mother sows had no effect on glucose absorption across the jejunal mucosa of suckling piglets. However, the dietary inulin supplementation after weaning increased the ΔIsc (P<0.001) compared with the controls

  15. [Intestinal absorption kinetics of flurbiprofen in rats].

    PubMed

    Peng, Jun-Jie; Lin, Cong-Cong; Li, Jiang; Zhu, Zhi-Hong; Yang, Xing-Gang; Pan, Wei-San

    2013-03-01

    To study the in situ intestinal absorption kinetics of flrubiprofen in rats, the absorption of flurbiprofen in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC. The effects of drug concentration on the intestinal absorption were investigated. The K(a) and P(app) values of flurbiprofen in the small intestine and colon had no significant difference (P > 0.05). Drug concentration (4.0, 10.0 and 16.0 mg x L(-1)) had no significant influence on the K(a) values (P > 0.05). However, when concentration was 4.0 mg x L(-1) and 10.0 mg x L(-1), significant effect on the P(app) values (P < 0.05) was found, but significant effect on the P(app) values was not shown between 10.0 mg x L(-1) and 16.0 mg x L(-1) (P > 0.05). The K(a) and P(app) values of flurbiprofen on the perfusion flow rate had significant difference (P < 0.05). Flurbiprofen could be absorbed at all segments of the intestine in rats and had no special absorption window. The absorption of flurbiprofen complies with the facilitated diffusion in the general intestinal segments, and accompany with the cytopsistransport mechanism probably. The perfusion flow rate had significant effect on the K(a) and P(app).

  16. Does apical membrane GLUT2 have a role in intestinal glucose uptake?

    PubMed Central

    Naftalin, Richard J

    2014-01-01

    It has been proposed that the non-saturable component of intestinal glucose absorption, apparent following prolonged exposure to high intraluminal glucose concentrations, is mediated via the low affinity glucose and fructose transporter, GLUT2, upregulated within the small intestinal apical border. The evidence that the non-saturable transport component is mediated via an apical membrane sugar transporter is that it is inhibited by phloretin, after exposure to phloridzin. Since the other apical membrane sugar transporter, GLUT5, is insensitive to inhibition by either cytochalasin B, or phloretin, GLUT2 was deduced to be the low affinity sugar transport route. As in its uninhibited state, polarized intestinal glucose absorption depends both on coupled entry of glucose and sodium across the brush border membrane and on the enterocyte cytosolic glucose concentration exceeding that in both luminal and submucosal interstitial fluids, upregulation of GLUT2 within the intestinal brush border will usually stimulate downhill glucose reflux to the intestinal lumen from the enterocytes; thereby reducing, rather than enhancing net glucose absorption across the luminal surface. These states are simulated with a computer model generating solutions to the differential equations for glucose, Na and water flows between luminal, cell, interstitial and capillary compartments. The model demonstrates that uphill glucose transport via SGLT1 into enterocytes, when short-circuited by any passive glucose carrier in the apical membrane, such as GLUT2, will reduce transcellular glucose absorption and thereby lead to increased paracellular flow. The model also illustrates that apical GLUT2 may usefully act as an osmoregulator to prevent excessive enterocyte volume change with altered luminal glucose concentrations. PMID:25671087

  17. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

    Dowling, H.J.; Offenbacher, E.G.; Pi-Sunyer, F.X.

    1986-03-01

    The mechanism of chromium (Cr) absorption by the rat small intestine was investigated using a double perfusion technique wherein the luman of the small intestine and the vasculature supplying it were separately perfused. The intestinal perfusate (IP) was a nutrient-rich tissue culture medium (TCM) with added inorganic Cr and /sup 51/Cr. The vascular perfusate (VP) was a Krebs-Ringer bicarbonate solution (KRB) containing 4.7% dextran, 0.1% glucose and 5% human serum. Cr absorption was calculated by the amount of /sup 51/Cr detected in the VP. To determine the transport mechanism for Cr, its absorption into the VP was measured at various Cr concentrations of the IP ranging from 10-400 ppb CrCl/sub 3/. The amount of Cr absorbed into the blood rose linearly with the intestinal Cr concentration suggesting a process of simple diffusion. Manipulations of the VP and IP constituents were made to investigate their effects on Cr absorption. When serum was omitted from the VP, Cr adsorption was suppressed, suggesting that serum component(s) are necessary for optimal Cr absorption. When either of 2 plasma transport proteins (apo-transferrin, albumin) were added to the serum-free VP at physiological levels, Cr absorption returned to, but did not exceed, control levels. When the TCM was replaced with a KRB solution; Cr absorption was suppressed indicating that there are nutrient(s) of the TCM which facilitate Cr absorption. Further suppression occurred when a Cr concentration gradient opposing Cr absorption was created (IP at 100 ppb Cr, VP at 400 ppb Cr).

  18. Glucose Transport into Everted Sacs of the Small Intestine of Mice

    ERIC Educational Resources Information Center

    Hamilton, Kirk L.; Butt, A. Grant

    2013-01-01

    The Na[superscript +]-glucose cotransporter is a key transport protein that is responsible for absorbing Na[superscript +] and glucose from the luminal contents of the small intestine and reabsorption by the proximal straight tubule of the nephron. Robert K. Crane originally described the cellular model of absorption of Na[superscript +] and…

  19. Circadian regulators of intestinal lipid absorption.

    PubMed

    Hussain, M Mahmood; Pan, Xiaoyue

    2015-04-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption.

  20. Heat Stress Reduces Intestinal Barrier Integrity and Favors Intestinal Glucose Transport in Growing Pigs

    PubMed Central

    Pearce, Sarah C.; Mani, Venkatesh; Boddicker, Rebecca L.; Johnson, Jay S.; Weber, Thomas E.; Ross, Jason W.; Rhoads, Robert P.; Baumgard, Lance H.; Gabler, Nicholas K.

    2013-01-01

    Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35–50% humidity; n = 8) or HS conditions (35°C; 24–43% humidity; n = 8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P = 0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P = 0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na+/K+ ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P = 0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport. PMID:23936392

  1. Heat stress reduces intestinal barrier integrity and favors intestinal glucose transport in growing pigs.

    PubMed

    Pearce, Sarah C; Mani, Venkatesh; Boddicker, Rebecca L; Johnson, Jay S; Weber, Thomas E; Ross, Jason W; Rhoads, Robert P; Baumgard, Lance H; Gabler, Nicholas K

    2013-01-01

    Excessive heat exposure reduces intestinal integrity and post-absorptive energetics that can inhibit wellbeing and be fatal. Therefore, our objectives were to examine how acute heat stress (HS) alters intestinal integrity and metabolism in growing pigs. Animals were exposed to either thermal neutral (TN, 21°C; 35-50% humidity; n=8) or HS conditions (35°C; 24-43% humidity; n=8) for 24 h. Compared to TN, rectal temperatures in HS pigs increased by 1.6°C and respiration rates by 2-fold (P<0.05). As expected, HS decreased feed intake by 53% (P<0.05) and body weight (P<0.05) compared to TN pigs. Ileum heat shock protein 70 expression increased (P<0.05), while intestinal integrity was compromised in the HS pigs (ileum and colon TER decreased; P<0.05). Furthermore, HS increased serum endotoxin concentrations (P=0.05). Intestinal permeability was accompanied by an increase in protein expression of myosin light chain kinase (P<0.05) and casein kinase II-α (P=0.06). Protein expression of tight junction (TJ) proteins in the ileum revealed claudin 3 and occludin expression to be increased overall due to HS (P<0.05), while there were no differences in claudin 1 expression. Intestinal glucose transport and blood glucose were elevated due to HS (P<0.05). This was supported by increased ileum Na(+)/K(+) ATPase activity in HS pigs. SGLT-1 protein expression was unaltered; however, HS increased ileal GLUT-2 protein expression (P=0.06). Altogether, these data indicate that HS reduce intestinal integrity and increase intestinal stress and glucose transport.

  2. Intestinal absorption and biomagnification of organochlorines

    SciTech Connect

    Gobas, F.A.P.C. ); McCorquodale, J.R.; Haffner, G.D. )

    1993-03-01

    Dietary uptake rates of several organochlorines from diets with different lipid contents were measured in goldfish (Carassius auratus) to investigate the mechanism of intestinal absorption and biomagnification of organic chemical. The results suggest that intestinal absorption is predominantly controlled by chemical diffusion rather than lipid cotransport. Data for chemical uptake in human infants are presented to illustrate that biomagnification is caused by the digestion of food in the gastrointestinal tract. The findings are discussed in the context of two conflicting theories for the mechanism of biomagnification, and a mechanistic model is presented for the dietary uptake and biomagnification of organic chemicals in fish and mammals.

  3. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  4. Molecular aspects of intestinal calcium absorption

    PubMed Central

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-01-01

    Intestinal Ca2+ absorption is a crucial physiological process for maintaining bone mineralization and Ca2+ homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca2+ across the brush border membranes (BBM) of enterocytes through epithelial Ca2+ channels TRPV6, TRPV5, and Cav1.3; Ca2+ movement from the BBM to the basolateral membranes by binding proteins with high Ca2+ affinity (such as CB9k); and Ca2+ extrusion into the blood. Plasma membrane Ca2+ ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca2+ from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca2+ transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca2+ transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca2+ absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca2+ transport to control values. Calcitriol [1,25(OH)2D3] is the major controlling hormone of intestinal Ca2+ transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca2+ transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)2D3 production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca2+ absorption according to Ca2+ demands. Better knowledge of the molecular details of intestinal Ca2+ absorption could lead to the development of

  5. Molecular aspects of intestinal calcium absorption.

    PubMed

    Diaz de Barboza, Gabriela; Guizzardi, Solange; Tolosa de Talamoni, Nori

    2015-06-21

    Intestinal Ca(2+) absorption is a crucial physiological process for maintaining bone mineralization and Ca(2+) homeostasis. It occurs through the transcellular and paracellular pathways. The first route comprises 3 steps: the entrance of Ca(2+) across the brush border membranes (BBM) of enterocytes through epithelial Ca(2+) channels TRPV6, TRPV5, and Cav1.3; Ca(2+) movement from the BBM to the basolateral membranes by binding proteins with high Ca(2+) affinity (such as CB9k); and Ca(2+) extrusion into the blood. Plasma membrane Ca(2+) ATPase (PMCA1b) and sodium calcium exchanger (NCX1) are mainly involved in the exit of Ca(2+) from enterocytes. A novel molecule, the 4.1R protein, seems to be a partner of PMCA1b, since both molecules co-localize and interact. The paracellular pathway consists of Ca(2+) transport through transmembrane proteins of tight junction structures, such as claudins 2, 12, and 15. There is evidence of crosstalk between the transcellular and paracellular pathways in intestinal Ca(2+) transport. When intestinal oxidative stress is triggered, there is a decrease in the expression of several molecules of both pathways that inhibit intestinal Ca(2+) absorption. Normalization of redox status in the intestine with drugs such as quercetin, ursodeoxycholic acid, or melatonin return intestinal Ca(2+) transport to control values. Calcitriol [1,25(OH)₂D₃] is the major controlling hormone of intestinal Ca(2+) transport. It increases the gene and protein expression of most of the molecules involved in both pathways. PTH, thyroid hormones, estrogens, prolactin, growth hormone, and glucocorticoids apparently also regulate Ca(2+) transport by direct action, indirect mechanism mediated by the increase of renal 1,25(OH)₂D₃ production, or both. Different physiological conditions, such as growth, pregnancy, lactation, and aging, adjust intestinal Ca(2+) absorption according to Ca(2+) demands. Better knowledge of the molecular details of intestinal Ca(2

  6. Physiology of Intestinal Absorption and Secretion.

    PubMed

    Kiela, Pawel R; Ghishan, Fayez K

    2016-04-01

    Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipid- and water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms. PMID:27086882

  7. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens.

    PubMed

    Awad, W A; Ghareeb, K; Zentek, J

    2014-10-01

    Deoxynivalenol (DON), a major contaminant of cereals and grains, is of public health concern worldwide and has been shown to reduce the electrogenic transport of glucose. However, the full effects of Fusarium mycotoxins on nutrient absorption are still not clear. The aim of this study was to investigate whether decreased nutrient absorption was due to specific effects on transporter trafficking in the intestine and whether inhibition of phosphoinositol-3-kinase (PI-3-kinase) affected the electrogenic jejunal transport of glucose. Jejunal mucosa of 6-week-old broiler chickens were mounted in Ussing chambers and treated with DON, wortmannin (a specific inhibitor of PI-3-kinase), DON + wortmannin, phlorizin and cytochalasin B. DON was found to decrease the short-circuit current (Isc) after glucose addition. A similar decline in Isc after glucose addition was observed following pre-application of wortmannin, or phlorizin (Na(+)/glucose co-transporter, SGLT1 inhibitor). The results indicate that DON decreased glucose absorption in the absence of wortmannin or phlorizin but had no additional effect on glucose absorption in their presence. Glucose transport was not affected by cytochalasin B (facilitative glucose transporter, GLUT2 inhibitor). The study provides evidence that the suppressive effect of DON on the electrogenic transport of glucose may be due to an inhibitory activity of the PI3 kinase pathway and intestinal SGLT1. Furthermore, the effect of cytochalasin B on glucose transport in chicken tissues differs from that in mammals. PMID:25011710

  8. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens.

    PubMed

    Awad, W A; Ghareeb, K; Zentek, J

    2014-10-01

    Deoxynivalenol (DON), a major contaminant of cereals and grains, is of public health concern worldwide and has been shown to reduce the electrogenic transport of glucose. However, the full effects of Fusarium mycotoxins on nutrient absorption are still not clear. The aim of this study was to investigate whether decreased nutrient absorption was due to specific effects on transporter trafficking in the intestine and whether inhibition of phosphoinositol-3-kinase (PI-3-kinase) affected the electrogenic jejunal transport of glucose. Jejunal mucosa of 6-week-old broiler chickens were mounted in Ussing chambers and treated with DON, wortmannin (a specific inhibitor of PI-3-kinase), DON + wortmannin, phlorizin and cytochalasin B. DON was found to decrease the short-circuit current (Isc) after glucose addition. A similar decline in Isc after glucose addition was observed following pre-application of wortmannin, or phlorizin (Na(+)/glucose co-transporter, SGLT1 inhibitor). The results indicate that DON decreased glucose absorption in the absence of wortmannin or phlorizin but had no additional effect on glucose absorption in their presence. Glucose transport was not affected by cytochalasin B (facilitative glucose transporter, GLUT2 inhibitor). The study provides evidence that the suppressive effect of DON on the electrogenic transport of glucose may be due to an inhibitory activity of the PI3 kinase pathway and intestinal SGLT1. Furthermore, the effect of cytochalasin B on glucose transport in chicken tissues differs from that in mammals.

  9. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states.

    PubMed

    Naftalin, Richard J

    2016-01-01

    A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD), non-alcoholic steatohepatitis, (NASH) and type 2 diabetes mellitus, (T2DM) demonstrates how when glucagon-like peptide-1, (GLP-1) is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA) blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU). When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic implications on GLP

  10. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states

    PubMed Central

    Naftalin, Richard J.

    2016-01-01

    A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD), non-alcoholic steatohepatitis, (NASH) and type 2 diabetes mellitus, (T2DM) demonstrates how when glucagon-like peptide-1, (GLP-1) is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA) blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU). When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic implications on GLP

  11. Normal and abnormal intestinal absorption by humans

    PubMed Central

    Heizer, William D.

    1979-01-01

    Adults eating a Western diet digest and absorb ingested food containing approximately 100 g fat, 350 g carbohydrate, and 75 g protein daily. Normal fat absorption requires adequate gastric, pancreatic, liver-biliary, mucosal, and lymphatic function. Carbohydrate and protein absorption is much less dependent on liver-biliary and lymphatic function. The intestine has a large reserve capacity for digestion and absorption of nutrients which is due to both excess function and to adaptive changes which increase function in one segment of the digestive-absorptive system when it is decreased or lost in another segment. The large reserve capacity explains why most of the prevalent intestinal diseases seldom cause clinically detectable changes in absorption. However, there are more than 30 less-common human diseases which cause malabsorption of one or more nutrients. Those that cause the malabsorption syndrome, i.e., steatorrhea and weight loss, can be conveniently categorized according to the major deficiency leading to the absorptive defect as follows: insufficient pancreatic enzyme activity, insufficient bile acid, disease of the small intestinal wall, multiple defects, mechanism unknown, and drug-induced malabsorption. A few diseases, most of which are congenital, cause malabsorption of only one or a few related nutrients such as lactose malabsorption in lactase deficiency. Most of the tests currently in use for detecting and diagnosing the cause of malabsorption are relatively insensitive and nonspecific. Chemical analysis of the fat in a three-day stool collection remains the single best test for diagnosing the malabsorption syndrome. However, a breath test using Triolein labeled with either the radioactive or stable isotope of carbon may be an important recent advance. Other breath tests are also currently being investigated for quantitating absorption or malabsorption of various substances including bile acids and various sugars. Studies of the function of the

  12. Glucose stimulates calcium-activated chloride secretion in small intestinal cells.

    PubMed

    Yin, Liangjie; Vijaygopal, Pooja; MacGregor, Gordon G; Menon, Rejeesh; Ranganathan, Perungavur; Prabhakaran, Sreekala; Zhang, Lurong; Zhang, Mei; Binder, Henry J; Okunieff, Paul; Vidyasagar, Sadasivan

    2014-04-01

    The sodium-coupled glucose transporter-1 (SGLT1)-based oral rehydration solution (ORS) used in the management of acute diarrhea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements and isotope flux measurements in Ussing chambers were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells. Confocal fluorescence laser microscopy and immunohistochemistry measured intracellular changes in calcium, sodium-glucose linked transporter, and calcium-activated chloride channel (anoctamin 1) expression. In addition to enhancing active sodium absorption, glucose increased intracellular calcium and stimulated electrogenic chloride secretion. Calcium imaging studies showed increased intracellular calcium when intestinal cells were exposed to glucose. Niflumic acid, but not glibenclamide, inhibited glucose-stimulated chloride secretion in mouse small intestines and in Caco-2 cells. Glucose-stimulated chloride secretion was not seen in ileal tissues incubated with the intracellular calcium chelater BAPTA-AM and the sodium-potassium-2 chloride cotransporter 1 (NKCC1) blocker bumetanide. These observations establish that glucose not only stimulates active Na absorption, a well-established phenomenon, but also induces a Ca-activated chloride secretion. This may explain the failure of glucose-based ORS to markedly reduce stool output in acute diarrhea. These results have immediate potential to improve the treatment outcomes for acute and/or chronic diarrheal diseases by replacing glucose with compounds that do not stimulate chloride secretion.

  13. [An inhibitory analysis of the role of the enterocyte cytoskeleton in the absorption of food substances in the small intestine].

    PubMed

    Morozov, I A; Verina, T Iu

    1993-06-01

    The effect of colchicine and cytochalasin B and D on the process of glucose and plant oil absorption in the small intestine of rats was studied using the light and electron microscopy and biochemical methods. The colchicine and CB, CD action on the elements of enterocytes' apical contractile complex and cytoskeleton inhibited the absorption thus suggesting the major role of endocytosis in the process of nutrients absorption in the small intestine.

  14. Intestinal glucose transport and salinity adaptation in a euryhaline teleost

    SciTech Connect

    Reshkin, S.J.; Ahearn, G.A.

    1987-03-01

    Glucose transport by upper and lower intestinal brush-border membrane vesicles of the African tilapia (Oreochromis mossambicus) was characterized in fish acclimated to either freshwater of full-strength sea water. D-(/sup 3/H)-glucose uptake by vesicles was stimulated by a transmembrane Na gradient, was electrogenic, and was enhanced by countertransport of either D-glucose or D-galactose. Glucose transport was greater in the upper intestine than in the lower intestine and in sea water animals rather than in fish acclimated to freshwater. Glucose influx (10-s uptake) involved both saturable and nonsaturable transport components. Sea water adaptation increased apparent glucose influx K/sub t/, J/sub max/, apparent diffusional permeability (P), and the apparent Na affinity of the cotransport system in both intestinal segments, but the stoichiometry of Na-glucose transfer (1:1) was unaffected by differential saline conditions or gut region. It is suggested that increased sugar transport in sea water animals is due to the combination of enhanced Na-binding properties and an increase in number or transfer rate of the transport proteins. Freshwater animals compensate for reduced Na affinity of the coupled process by markedly increasing the protein affinity for glucose.

  15. Intestinal absorption of biotin in the rat

    SciTech Connect

    Bowman, B.B.; Selhub, J.; Rosenberg, I.H.

    1986-07-01

    We examined the absorption of biotin using the in vivo intestinal loop technique. Jejunal segments from male rats were filled with solutions containing (/sup 3/H)biotin and (/sup 14/C)inulin in Krebs-Ringer phosphate buffer, pH 6.5. Absorption was determined on the basis of luminal tritium disappearance after correction for inulin recovery. At biotin concentrations of 0.1 and 5.0 microM, luminal biotin disappearance was linear for at least 10 min. At biotin concentrations ranging from 2.3 nM to 75 microM, 10-28% of the administered dose was absorbed in 10 min. The concentration dependence of luminal biotin disappearance is consistent with the presence of both saturable and nonsaturable (linear) components of biotin uptake, with estimated Km = 9.6 microM and Jmax = 75.2 pmol/(2.5 cm loop X min). The rate constant for nonsaturable uptake is 3.1 pmol/(2.5 cm loop X min X microM). We conclude that at biotin concentrations less than 5 microM, biotin absorption proceeds largely by the saturable process, whereas at concentrations above 25 microM, nonsaturable uptake predominates. Additional studies demonstrated significantly less biotin uptake in the ileum than in the jejunum, a finding in agreement with previous in vitro studies.

  16. Foregut exclusion disrupts intestinal glucose sensing and alters portal nutrient and hormonal milieu.

    PubMed

    Pal, Atanu; Rhoads, David B; Tavakkoli, Ali

    2015-06-01

    The antidiabetes effects of Roux-en-Y gastric bypass (RYGB) are well-known, but the underlying mechanisms remain unclear. Isolating the proximal small intestine, and in particular its luminal glucose sensors, from the nutrient stream has been proposed as a critical change, but the pathways involved are unclear. In a rodent model, we tested the effects of isolating and then stimulating a segment of proximal intestine using glucose analogs to examine their impact on glucose absorption (Gabsorp) and hormone secretion after a glucose bolus into the distal jejunum. Analogs selective for sodium-glucose cotransporter (SGLT) family members and the sweet taste receptor were tested, and measurements of the portosystemic gradient were used to determine Gabsorp and hormone secretion, including GLP-1. Proximal intestinal isolation reduced Gabsorp and GLP-1 secretion. Stimulation of the glucose-sensing protein SGLT3 increased Gabsorp and GLP-1 secretion. These effects were abolished by vagotomy. Sweet taste receptor stimulation only increased GLP-1 secretion. This study suggests a novel role for SGLT3 in coordinating intestinal function, as reflected by the concomitant modulation of Gabsorp and GLP-1 secretion, with these effects being mediated by the vagus nerve. Our findings provide potential mechanistic insights into foregut exclusion in RYGB and identify SGLT3 as a possible antidiabetes therapeutic target.

  17. Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine.

    PubMed

    Lv, Xiao-Yan; Li, Jing; Zhang, Ming; Wang, Chun-Mei; Fan, Zheng; Wang, Chun-Yan; Chen, Li

    2010-03-01

    Berberine, a plant alkaloid used in traditional Chinese medicine, has a wide spectrum of pharmacological actions, but the poor bioavailability limits its clinical use. The present aim was to observe the effects of sodium caprate on the intestinal absorption and antidiabetic action of berberine. The in situ, in vitro, and in vivo models were used to observe the effect of sodium caprate on the intestinal absorption of berberine. Intestinal mucosa morphology was measured to evaluate the toxic effect of sodium caprate. Diabetic model was used to evaluate antidiabetic effect of berberine coadministered with sodium caprate. The results showed that the absorption of berberine in the small intestine was poor and that sodium caprate could significantly improve the poor absorption of berberine in the small intestine. Sodium caprate stimulated mucosal-to-serosal transport of berberine; the enhancement ratios were 2.08, 1.49, and 3.49 in the duodenum, jejunum, and ileum, respectively. After coadministration, the area under the plasma concentration-time curve of berberine was increased 28% than that in the absence of sodium caprate. Furthermore, both berberine and coadministration with sodium caprate orally could significantly decrease fasting blood glucose and improve glucose tolerance in diabetic rats (P < 0.05). The hypoglycemic effect of coadministration group was remarkably stronger, and the areas under the glucose curves was decreased 22.5%, compared with berberine treatment group (P < 0.05). Morphologic analysis indicated that sodium caprate was not significantly injurious to the intestinal mucosa. The study demonstrates that sodium caprate could significantly promote the absorption of berberine in intestine and enhance its antidiabetic effect without any serious mucosal damage.

  18. Aqueous extract of Abutilon indicum Sweet inhibits glucose absorption and stimulates insulin secretion in rodents.

    PubMed

    Krisanapun, Chutwadee; Peungvicha, Penchom; Temsiririrkkul, Rungravi; Wongkrajang, Yuvadee

    2009-08-01

    The objective of this study was to evaluate the antidiabetic effects of the aqueous extract derived from the Thai Abutilon indicum Sweet plant and to explore its effects on intestinal glucose absorption and insulin secretion. The authors hypothesized that the plasma glucose level could be reduced through the inhibition of glucose absorption and/or the enhancement of insulin secretion. Administration of the extract (0.5 and 1 g/kg body weight) in an oral glucose tolerance test led to a significant reduction in plasma glucose levels in 30 minutes after the administration in moderately diabetic rats, as compared with untreated rats (P < .05), and this was at a faster rate than the use of an antidiabetic drug, glibenclamide. The inhibition of glucose absorption through the small intestine was investigated using an everted intestinal sac. The results showed that the extract at concentrations of 0.156 to 5 mg/mL caused a reduction of glucose absorption in a dose response manner. The maximum response was noted at a dose of 2.5 mg/mL. The promotion of the extract on insulin secretion was confirmed by incubating beta cell of pancreatic islets and INS-1E insulinoma cells with the extract at 1 to 1000 microg/mL. These observations suggest that the aqueous extract from the A indicum plant has antidiabetic properties, which inhibited glucose absorption and stimulated insulin secretion. Phytochemical screening also revealed that the extract contained alkaloids, flavonoids, tannins, glycosides, and saponins that could account for the observed pharmacologic effects of the plant extract. PMID:19761892

  19. Influence of peppermint oil on absorptive and secretory processes in rat small intestine.

    PubMed Central

    Beesley, A; Hardcastle, J; Hardcastle, P T; Taylor, C J

    1996-01-01

    BACKGROUND: Peppermint oil is used to relieve the symptoms of irritable bowel syndrome, relaxing intestinal smooth muscle by reducing the availability of calcium, but its effects on intestinal transport are unknown. AIMS: To determine the effect of peppermint oil on intestinal transport processes. METHODS: The influence of peppermint oil on intestinal transport was investigated in rat jejunum using both intestinal sheets mounted in Ussing chambers and brush border membrane vesicles. RESULTS: Mucosal peppermint oil (1 and 5 mg/ml) had no significant effect on basal short circuit current, but inhibited the increase associated with sodium dependent glucose absorption. The increased short circuit current induced by serosal acetylcholine, a reflection of calcium mediated electrogenic chloride secretion, was unaffected by mucosal peppermint oil (5 mg/ml). In contrast, serosal peppermint oil (1 mg/ml) inhibited the response to acetylcholine without reducing the effect of mucosal glucose. In brush border membrane vesicles active glucose uptake was inhibited by extravesicular peppermint oil at concentrations of 0.5 and 1 mg/ml. CONCLUSIONS: Peppermint oil in the intestinal lumen inhibits enterocyte glucose uptake via a direct action at the brush border membrane. Inhibition of secretion by serosal peppermint oil is consistent with a reduced availability of calcium. PMID:8991859

  20. Hydrolysis-dependent absorption of disaccharides in the rat small intestine (chronic experiments and mathematical modeling).

    PubMed

    Gromova, L V; Gruzdkov, A A

    1999-06-01

    In order to throw light on the mechanisms responsible for the enzyme-dependent absorption of disaccharides membrane hydrolysis of maltose and trehalose and the absorption of glucose (free and that derived from disaccharides) were studied in isolated loops (20 cm) of the rat small intestine in chronic experiments. The rates of glucose absorption were 0.26-0.81 micromol x min(-1) x cm(-1) when the loop was perfused with a 12.5 to 75.0 mmol/l free glucose solution, which is only insignificantly higher than the rates observed during perfusion with equivalent maltose solutions. The coupling coefficient (the ratio of glucose absorption rate to the rate of disaccharide hydrolysis) decreased from 0.90 to 0.60 with the increasing maltose concentrations in the infusate from 6.25 to 37.5 mmol/l, but remained unchanged (approximately 0.95) within the same range of trehalose concentrations. The permeability of the pre-epithelial barrier was equivalent to that of unstirred water layer of less than 40 microm thickness. Fluid absorption was within the range of 0.73-2.55 microl x min(-1) x cm(-1), and it showed a correlation with the rates of glucose absorption. The results agree with a model developed on the assumption that free glucose and that released from disaccharides share the same membrane transporters. It could be concluded that a close coupling of disaccharide hydrolysis with derived glucose absorption in chronic experiments is achieved mainly due to a high activity of glucose transporters, which are presumably not associated with membrane disaccharidases. The transcellular active transport is a predominant mechanism of disaccharide-derived glucose absorption under conditions close to physiological.

  1. [Intestinal absorption kinetics of Polygonum capitatum extract in rats].

    PubMed

    Yang, Wu; Hou, Jia; Lu, Yuan; Chen, Peng-cheng; Liao, Shang-gao; Huang, Yong

    2015-11-01

    A UPLC-ESI-MS/MS method was used to determinate the main active fractions gallic acid, protocatechuic acid, myricetrin, hyperoside and quercitrin in Polygonum capitatum extracts by in situ intestinal perfusion models; the absorption rate constants and cumulative penetration rate of absorption were calculated. The effect of different drug concentrations, different intestine segments, bile and P-gp inhibitors on the absorption mechanism of Gallic acid and other compositions in P. capitatum extracts. The experimental results showed that gallic acid, protocatechuic acid, myricetrin and quercitrin were observed saturated at high concentration (P < 0.05). Bile had significant inhibition effect on protocatechuic acid absorption and had promotion effect on myricetrin and hyperoside absorption (P < 0.05). P-gp inhibitor verapamil could significantly enhance the absorption of Protocatechuic acid (P < 0.05). The overall trend for absorption of various compositions was that small intestine > colon. This indicated that the absorption mechanism of P. capitatum extracts in rat intestine was in line with fist-order kinetics characteristics. The composition could be absorbed in all of the different intestinal segments, and the absorption was mainly concentrated in small intestine. The protocatechuic acid may be the substrate of P-gp.

  2. [Intestinal absorption kinetics of Polygonum capitatum extract in rats].

    PubMed

    Yang, Wu; Hou, Jia; Lu, Yuan; Chen, Peng-cheng; Liao, Shang-gao; Huang, Yong

    2015-11-01

    A UPLC-ESI-MS/MS method was used to determinate the main active fractions gallic acid, protocatechuic acid, myricetrin, hyperoside and quercitrin in Polygonum capitatum extracts by in situ intestinal perfusion models; the absorption rate constants and cumulative penetration rate of absorption were calculated. The effect of different drug concentrations, different intestine segments, bile and P-gp inhibitors on the absorption mechanism of Gallic acid and other compositions in P. capitatum extracts. The experimental results showed that gallic acid, protocatechuic acid, myricetrin and quercitrin were observed saturated at high concentration (P < 0.05). Bile had significant inhibition effect on protocatechuic acid absorption and had promotion effect on myricetrin and hyperoside absorption (P < 0.05). P-gp inhibitor verapamil could significantly enhance the absorption of Protocatechuic acid (P < 0.05). The overall trend for absorption of various compositions was that small intestine > colon. This indicated that the absorption mechanism of P. capitatum extracts in rat intestine was in line with fist-order kinetics characteristics. The composition could be absorbed in all of the different intestinal segments, and the absorption was mainly concentrated in small intestine. The protocatechuic acid may be the substrate of P-gp. PMID:27071271

  3. [The absorption and metabolism of oxymatrine in rat intestine].

    PubMed

    Cai, Li-yun; Wu, Li-li; Yu, Xiao-ming; Liu, Jun-jin; Han, Wei-chao; Wei, Qiang; Tang, Lan

    2015-10-01

    The purpose of this study is to systematically investigate the characteristics of absorption and metabolism of oxymatrine (OMT) using rat intestinal perfusion model. Ultra performance liquid chromatography (UPLC) and high performance liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry (HPLC-ESI(+)-Q-TOF-MS) were used to test absorption of OMT in intestine at 100, 200 and 400 µmol · L(-1). The absorption rate and permeability of OMT is not dependent on concentration, but through passive absorption in intestine (P > 0.05). In the rat intestine, the absorbed amount of OMT was significantly different in four sections of the intestine in an order of duodenum > jejunum > ileum > colon (P < 0.05). OMT is metabolized into two metabolites in duodenum and jejunum, and matrine (MT) is the major one.

  4. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    PubMed

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.

  5. Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.

    PubMed

    Xie, Ping; Guo, Feng; Ma, Yinyan; Zhu, Hongling; Wang, Freddy; Xue, Bingzhong; Shi, Hang; Yang, Jian; Yu, Liqing

    2014-01-01

    Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes. PMID:24618586

  6. Clay ingestion enhances intestinal triacylglycerol hydrolysis and non-esterified fatty acid absorption.

    PubMed

    Habold, Caroline; Reichardt, François; Le Maho, Yvon; Angel, Fabielle; Liewig, Nicole; Lignot, Jean-Hervé; Oudart, Hugues

    2009-07-01

    Consumption by animals and humans of earthy materials such as clay is often related to gut pathologies. Our aim was to determine the impact of kaolinite ingestion on glucose and NEFA transport through the intestinal mucosa. The expression of hexose transporters (Na/glucose co-transporter 1 (SGLT1), GLUT2, GLUT5) and of proteins involved in NEFA absorption (fatty acid transporter/cluster of differentiation 36 (FAT/CD36), fatty acid transport protein 4 (FATP4) and liver fatty acid binding protein (L-FABP)) was measured (1) in rats whose jejunum was perfused with a solution of kaolinite, and (2) in rats who ate spontaneously kaolinite pellets during 7 and 28 d. Also, we determined TAG and glucose absorption in the kaolinite-perfused group, and pancreatic lipase activity, gastric emptying and intestinal transit in rats orally administered with kaolinite. Glucose absorption was not affected by kaolinite perfusion or ingestion. However, kaolinite induced a significant increase in intestinal TAG hydrolysis and NEFA absorption. The cytoplasmic expression of L-FABP and FATP4 also increased due to kaolinite ingestion. NEFA may enter the enterocytes via endocytosis mainly since expression of NEFA transporters in the brush-border membrane was not affected by kaolinite. After uptake, rapid binding of NEFA by L-FABP and FATP4 could act as an intracellular NEFA buffer to prevent NEFA efflux. Increased TAG hydrolysis and NEFA absorption may be due to the adsorption properties of clay and also because kaolinite ingestion caused a slowing down of gastric emptying and intestinal transit.

  7. Glucose-lowering effects of intestinal bile acid sequestration through enhancement of splanchnic glucose utilization.

    PubMed

    Prawitt, Janne; Caron, Sandrine; Staels, Bart

    2014-05-01

    Intestinal bile acid (BA) sequestration efficiently lowers plasma glucose concentrations in type 2 diabetes (T2D) patients. Because BAs act as signaling molecules via receptors, including the G protein-coupled receptor TGR5 and the nuclear receptor FXR (farnesoid X receptor), to regulate glucose homeostasis, BA sequestration, which interrupts the entero-hepatic circulation of BAs, constitutes a plausible action mechanism of BA sequestrants. An increase of intestinal L-cell glucagon-like peptide-1 (GLP-1) secretion upon TGR5 activation is the most commonly proposed mechanism, but recent studies also argue for a direct entero-hepatic action to enhance glucose utilization. We discuss here recent findings on the mechanisms of sequestrant-mediated glucose lowering via an increase of splanchnic glucose utilization through entero-hepatic FXR signaling.

  8. Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

    PubMed Central

    Færch, Kristine; Pacini, Giovanni; Nolan, John J.; Hansen, Torben; Tura, Andrea; Vistisen, Dorte

    2013-01-01

    OBJECTIVE We studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin sensitivity and β-cell function measured by gold-standard tests were reflected in the corresponding OGTT-derived estimates. RESEARCH DESIGN AND METHODS With validated methods, various aspects of glucose absorption were estimated from 12-point, 3-h, 75-g OGTTs in 66 individuals with normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Insulin sensitivity and β-cell function were measured with the euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance tests, respectively. Surrogate markers of both conditions were calculated from OGTTs. RESULTS More rapid glucose absorption (P ≤ 0.036) and reduced late glucose absorption (P ≤ 0.039) were observed in the i-IFG group relative to NGT and i-IGT groups. Women with i-IGT had a lower early glucose absorption than did men with i-IGT (P = 0.041); however, this difference did not persist when differences in body size were taken into account (P > 0.28). Faster glucose absorption was related to higher fasting (P = 0.001) and lower 2-h (P = 0.001) glucose levels and to greater height and fat-free mass (P < 0.001). All OGTT-derived measures of insulin sensitivity, but only one of three measures of β-cell function, reflected the differences for these parameters between those with normal and impaired glucose regulation as measured by gold-standard tests. CONCLUSIONS Glucose absorption patterns during an OGTT are significantly related to plasma glucose levels and body size, which should be taken into account when estimating β-cell function from OGTTs in epidemiological studies. PMID:24062321

  9. Bioavailability and intestinal absorption of aluminum in rats: effects of aluminum compounds and some dietary constituents.

    PubMed

    Cunat, L; Lanhers, M C; Joyeux, M; Burnel, D

    2000-07-01

    In the present investigation, the deposition of aluminum in intestinal fragment and the appearance in blood were studied in a perfused rat intestine in situ for 1 h with several aluminum forms (16 mM). We observed that aluminum absorption was positively correlated with the theoretic affinity of aluminum and the functional groups of the chelating agent. The absorption of aluminum after ingestion of organic compounds is more important than after ingestion of mineral compounds, with the following order: Al citrate > Al tartrate, Al gluconate, Al lactate > Al glutamate, Al chloride, Al sulfate, Al nitrate. Absorption depends on the nature of the ligands associated with the Al3+ ion in the gastrointestinal fluid. The higher the aluminum retention in intestinal fragment, the lower the absorption and appearance in blood. However, the higher aluminum concentration is always in the jejunal fragment because of the influence of pH variation on this fragment. Another objective of the present study was to determine the influence of several parameters on aluminum citrate absorption: with or without 0.1 mmol dinitrophenol/L, with aluminum concentration from 3.2, 16, 32, and 48, to 64 mmol/L, media containing 0, 3, or 6 mmol Ca/L, with or without phosphorus or glucose. It is concluded that aluminum is absorbed from the gastrointestinal tract by (1) a paracellular energy independent and nonsaturable route, mainly used for high aluminum concentration, which is modified by extracellular calcium, and (2) a transcellular and saturable route, the aluminum level was not modified with enhancement of aluminum quantity in intestinal lumen. This pathway can be similar with calcium transfer through the intestine and is energy dependent because of a decrease of aluminum absorption that follows the removal of glucose and phosphorus.

  10. Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters.

    PubMed

    Yamabe, Noriko; Kang, Ki Sung; Lee, Woojung; Kim, Su-Nam; Zhu, Bao Ting

    2015-03-01

    Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17β-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17β-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters.

  11. Enzymatic synthesis of 2-deoxyglucose-containing maltooligosaccharides for tracing the location of glucose absorption from starch digestion.

    PubMed

    Lee, Byung-Hoo; Koh, Dong-Wan; Territo, Paul R; Park, Cheon-Seok; Hamaker, Bruce R; Yoo, Sang-Ho

    2015-11-01

    The ileal brake mechanism which induces a potentially beneficial slower gastric emptying rate and increased satiety is triggered by macronutrients including glucose from glycemic carbohydrates. For optimization of this diet-induced health benefit, there is the need for a way to determine the location of glucose deposition in the small intestine. Labeled 2-deoxyglucose (2-DG) can be used to trace the location of glucose absorption due to its accumulative property in the small intestine enterocytes. However, because pure glucose, or 2-DG, is directly absorbed in the proximal small intestine, we designed 2-DG containing maltooligosaccharides (2-DG-MOs) that can be used with a mild α-glucosidase inhibitor to attain an analytical method for determining location-specific delivery of glucose and its physiological effect.

  12. Biopharmaceutics classification and intestinal absorption study of apigenin.

    PubMed

    Zhang, Jianjun; Liu, Dapeng; Huang, Yanting; Gao, Yuan; Qian, Shuai

    2012-10-15

    The aim of the study was to characterize the biopharmaceutics classification system (BCS) category of apigenin (AP) using intrinsic dissolution rate (IDR) and rat intestinal permeability, and to investigate the intestinal absorption mechanism of AP in rats. In the present investigation, equilibrium solubility and intrinsic dissolution rate (IDR) of AP were estimated in phosphate buffers. Effective intestinal permeability (P(eff)) of AP was determined using single-pass intestinal perfusion (SPIP) technique in four segments (duodenum, jejunum, ileum and colon) of rat intestine at three concentrations (10, 50 and 100 μg/ml). The aqueous solubility of AP in tested phosphate buffers was very poor with maximum solubility of 2.16 μg/ml at pH 7.5. The IDR of AP was very low with a value of 0.006 mg/min/cm(2). The minimum and maximum P(eff)s determined by SPIP were 0.198×10(-4) and 0.713×10(-4) cm/s at jejunum and duodenum site, respectively. In addition, the concentration-dependent permeability behavior was observed in the duodenum and jejunum, which suggested that AP was transported by both passive and active carrier-mediated saturable mechanism in these two intestinal segments. However, the observed concentration-independent permeability behavior in ileum and colon indicated primarily passive transport mechanism of absorption of AP in the last two intestinal segments. AP was classified as class II drug of the BCS due to its low solubility and high intestinal permeability. AP could be well absorbed in the whole intestine with the main absorption site at duodenum. The absorption of AP in four intestinal segments exhibited different transport mechanisms.

  13. Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans

    SciTech Connect

    Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

    1989-03-01

    The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

  14. Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption.

    PubMed

    Park, J H; Jin, J Y; Baek, W K; Park, S H; Sung, H Y; Kim, Y K; Lee, J; Song, D K

    2009-12-01

    Prolonged postprandial hyperglycemia is a detrimental factor for type 2 diabetes and obesity. The benefit of green tea extract (GTE) consumption still requires confirmation. We report the effects of circulating green tea catechins on blood glucose and insulin levels. Oral glucose loading 1 h after GTE ingestion in humans led to higher blood glucose and insulin levels than in control subjects. Gallated catechins were required for these effects, although within the intestinal lumen they have been known to decrease glucose and cholesterol absorption. Treatment with epigallocatechin-3-gallate hindered 2-deoxyglucose uptake into liver, fat, pancreatic beta-cell, and skeletal muscle cell lines. The glucose intolerance was ameliorated by gallated catechin-deficient GTE or GTE mixed with polyethylene glycol, which was used as an inhibitor of intestinal absorption of gallated catechins. These findings may suggest that the gallated catechin when it is in the circulation elevates blood glucose level by blocking normal glucose uptake into the tissues, resulting in secondary hyperinsulinemia, whereas it decreases glucose entry into the circulation when they are inside the intestinal lumen. These findings encourage the development of non-absorbable derivatives of gallated catechins for preventative treatment of type 2 diabetes and obesity, which would specifically induce only the positive luminal effect.

  15. Mathematical Modeling of Renal Tubular Glucose Absorption after Glucose Load

    PubMed Central

    De Gaetano, Andrea; Panunzi, Simona; Eliopoulos, Dimitris; Hardy, Thomas; Mingrone, Geltrude

    2014-01-01

    A partial differential Progressive Tubular Reabsorption (PTR) model, describing renal tubular glucose reabsorption and urinary glucose excretion following a glucose load perturbation, is proposed and fitted to experimental data from five subjects. For each subject the Glomerular Filtration Rate was estimated and both blood and urine glucose were sampled following an Intra-Venous glucose bolus. The PTR model was compared with a model representing the conventional Renal Threshold Hypothesis (RTH). A delay bladder compartment was introduced in both formulations. For the RTH model, the average threshold for glycosuria varied between 9.90±4.50 mmol/L and 10.63±3.64 mmol/L (mean ± Standard Deviation) under different hypotheses; the corresponding average maximal transport rates varied between 0.48±0.45 mmol/min (86.29±81.22 mg/min) and 0.50±0.42 mmol/min (90.62±76.15 mg/min). For the PTR Model, the average maximal transports rates varied between 0.61±0.52 mmol/min (109.57±93.77 mg/min) and 0.83±0.95 mmol/min (150.13±171.85 mg/min). The time spent by glucose inside the tubules before entering the bladder compartment varied between 1.66±0.73 min and 2.45±1.01 min. The PTR model proved much better than RTH at fitting observations, by correctly reproducing the delay of variations of glycosuria with respect to the driving glycemia, and by predicting non-zero urinary glucose elimination at low glycemias. This model is useful when studying both transients and steady-state glucose elimination as well as in assessing drug-related changes in renal glucose excretion. PMID:24489817

  16. Changing the unstirred water layer in the intestine and its effect on absorption

    SciTech Connect

    Lu, L.

    1988-01-01

    The purpose of this research was to examine possible methods for reducing the thickness of the unstirred water layer (UWL) in the canine intestinal lumen in vivo, and to determine the effects of any reduction obtained upon intestinal absorption. The experimental approaches employed in attempting to improve stirring of the luminal fluid include: (1) addition of oleic acid plus Na-taurocholate (OA + TC) or other bile salts to the fluid used to lavage the intestinal loops since the lavage with OA + TC has been found to increase the motility of the villi; (2) increasing the lavage flow rate to 100 ml/min; (3) introduction of air bubbles into the lavage fluid. The effect of these procedures on the UWL was determined by isotopic analysis of the tissue of the experimental intestinal segment for non-absorbable {sup 14}C-labeled inulin which was included in the lavage solutions. The effects of these procedures on intestinal absorption of water and glucose are examined by measuring the difference in the volumes and the concentrations of {sup 3}H-labeled glucose in the inflowing and outflowing fluids to the experimental segment.

  17. Middle infrared optoelectronic absorption systems for monitoring physiological glucose solutions

    NASA Astrophysics Data System (ADS)

    Martin, W. Blake

    Tight monitoring of the glucose levels for diabetic individuals is essential to control long-term complications. A definitive diabetes management system has yet to be developed for the diabetic. This research investigates the application of middle infrared absorption frequencies for monitoring glucose levels in biological solutions. Three frequencies were identified using a Fourier transform infrared spectrometer and correlated to changes in glucose concentrations. The 1035 +/- 1 cm-1 frequency was determined to be the best representative frequency. Other biological molecules contributed no significant interference to monitoring glucose absorption. A second frequency at 1193 cm-1 was suggested as a representative background absorption frequency, which could be used for more accurate glucose absorption values. Next, a quantum cascade laser optoelectronic absorption system was designed and developed to monitor glucose. After careful alignment and design, the system was used to monitor physiological glucose concentrations. Correlation at 1036 cm-1 with glucose changes was comparable to the previous results. The use of the background absorption frequency was verified. This frequency essentially acts as a calibrating frequency to adjust in real-time to any changes in the background absorption that may alter the accuracy of the predicted glucose value. An evanescent wave cavity ring-down spectroscopy technique was explored to monitor molecules in a biological solution. Visible light at 425 nm was used to monitor hemoglobin in control urine samples. An adsorption isotherm for hemoglobin was detectable to limit of 5.8 nM. Evanescent wave cavity ring-down spectroscopy would be useful for a glucose solution. Given an equivalent system designed for the middle infrared, the molar extinction coefficient of glucose allows for a detectable limit of 45 mg/dl for a free-floating glucose solution, which is below normal physiological concentrations. The future use of a hydrophobic

  18. Exploring food effects on indinavir absorption with human intestinal fluids in the mouse intestine.

    PubMed

    Holmstock, Nico; De Bruyn, Tom; Bevernage, Jan; Annaert, Pieter; Mols, Raf; Tack, Jan; Augustijns, Patrick

    2013-04-11

    Food can have a significant impact on the pharmacokinetics of orally administered drugs, as it may affect drug solubility as well as permeability. Since fed state conditions cannot easily be implemented in the presently available permeability tools, including the frequently used Caco-2 system, exploring food effects during drug development can be quite challenging. In this study, we investigated the effect of fasted and fed state conditions on the intestinal absorption of the HIV protease inhibitor indinavir using simulated and human intestinal fluids in the in situ intestinal perfusion technique in mice. Although the solubility of indinavir was 6-fold higher in fed state human intestinal fluids (FeHIF) as compared to fasted state HIF (FaHIF), the intestinal permeation of indinavir was 22-fold lower in FeHIF as compared to FaHIF. Dialysis experiments showed that only a small fraction of indinavir is accessible for absorption in FeHIF due to micellar entrapment, possibly explaining its low intestinal permeation. The presence of ritonavir, a known P-gp inhibitor, increased the intestinal permeation of indinavir by 2-fold in FaHIF, while there was no increase when using FeHIF. These data confirm that drug-food interactions form a complex interplay between solubility and permeability effects. The use of HIF in in situ intestinal perfusions holds great promise for biorelevant absorption evaluation as it allows to directly explore this complex solubility/permeability interplay on drug absorption.

  19. Effect of zinc supplements on the intestinal absorption of calcium

    SciTech Connect

    Spencer, H.; Rubio, N.; Kramer, L.; Norris, C.; Osis, D.

    1987-02-01

    Pharmacologic doses of zinc are widely used as zinc supplements. As calcium and zinc may compete for common absorption sites, a study was carried out on the effect of a pharmacologic dose of zinc on the intestinal absorption of calcium in adult males. The analyzed dietary zinc intake in the control studies was normal, averaging 14.6 mg/day. During the high zinc study, 140 mg zinc as the sulfate was added daily for time periods ranging from 17 to 71 days. The studies were carried out during both a low calcium intake averaging 230 mg/day and during a normal calcium intake of 800 mg/day. Calcium absorption studies were carried out during the normal and high zinc intake by using an oral tracer dose of Ca-47 and determining plasma levels and urinary and fecal excretions of Ca-47. The study has shown that, during zinc supplementation, the intestinal absorption of calcium was significantly lower during a low calcium intake than in the control study, 39.3% vs 61% respectively, p less than 0.001. However, during a normal calcium intake of 800 mg/day, the high zinc intake had no significant effect on the intestinal absorption of calcium. These studies have shown that the high zinc intake decreased the intestinal absorption of calcium during a low calcium intake but not during a normal calcium intake.

  20. Intestinal absorption of magnesium from food and supplements.

    PubMed Central

    Fine, K D; Santa Ana, C A; Porter, J L; Fordtran, J S

    1991-01-01

    The purpose of this study was to measure magnesium absorption over the wide range of intakes to which the intestine may be exposed from food and/or magnesium-containing medications. Net magnesium absorption was measured in normal subjects after they ingested a standard meal supplemented with 0, 10, 20, 40, and 80 mEq of magnesium acetate. Although absorption increased with each increment in intake, fractional magnesium absorption fell progressively (from 65% at the lowest to 11% at the highest intake) so that absorption as a function of intake was curvilinear. This absorption-intake relationship was almost perfectly represented by an equation containing a hyperbolic function plus a linear function. Our results are statistically compatible with a magnesium absorption process that simultaneously uses a mechanism that reaches an absorptive maximum, plus a mechanism that endlessly absorbs a defined fraction (7%) of ingested magnesium. Compared to previous studies of calcium absorption, much less magnesium that calcium was absorbed at intakes above 8 mEq/meal, apparently due to greater restriction of intestinal permeability to magnesium. We also found that magnesium from a high magnesium-containing food source, almonds, was just as bioavailable as from soluble magnesium acetate. In contrast, magnesium absorption from commercially available enteric-coated magnesium chloride was much less than from magnesium acetate, suggesting that enteric coating can impair magnesium bioavailability. PMID:1864954

  1. Microbiota-Produced Succinate Improves Glucose Homeostasis via Intestinal Gluconeogenesis.

    PubMed

    De Vadder, Filipe; Kovatcheva-Datchary, Petia; Zitoun, Carine; Duchampt, Adeline; Bäckhed, Fredrik; Mithieux, Gilles

    2016-07-12

    Beneficial effects of dietary fiber on glucose and energy homeostasis have long been described, focusing mostly on the production of short-chain fatty acids by the gut commensal bacteria. However, bacterial fermentation of dietary fiber also produces large amounts of succinate and, to date, no study has focused on the role of succinate on host metabolism. Here, we fed mice a fiber-rich diet and found that succinate was the most abundant carboxylic acid in the cecum. Dietary succinate was identified as a substrate for intestinal gluconeogenesis (IGN), a process that improves glucose homeostasis. Accordingly, dietary succinate improved glucose and insulin tolerance in wild-type mice, but those effects were absent in mice deficient in IGN. Conventional mice colonized with the succinate producer Prevotella copri exhibited metabolic benefits, which could be related to succinate-activated IGN. Thus, microbiota-produced succinate is a previously unsuspected bacterial metabolite improving glycemic control through activation of IGN. PMID:27411015

  2. In vivo studies of biotin absorption in distal rat intestine

    SciTech Connect

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  3. Oat β-glucan depresses SGLT1- and GLUT2-mediated glucose transport in intestinal epithelial cells (IEC-6).

    PubMed

    Abbasi, Nazanin N; Purslow, Peter P; Tosh, Susan M; Bakovic, Marica

    2016-06-01

    Oat β-glucan consumption is linked to reduced risk factors associated with diabetes and obesity by lowering glycemic response and serum level of low-density lipoproteins. The purpose of this study was to identify the mechanism of action of oat β-glucan at the interface between the gut wall and the lumen responsible for attenuating glucose levels. We proposed that viscous oat β-glucan acts as a physical barrier to glucose uptake in normally absorptive gut epithelial cells IEC-6 by affecting the expression of intestinal glucose transporters. Concentration and time-dependent changes in glucose uptake were established by using a nonmetabolizable glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose. The effectiveness of nutrient transport in IEC-6 cells was shown by significant differences in glucose uptake and corresponding transporter expression. The expressions of glucose transporters sodium-glucose-linked transport protein 1 (SGLT1) and glucose transporter 2 (GLUT2) increased with time (0-60 minutes) and glucose levels (5-25 mmol/L). The suppression of glucose uptake and SGLT1 and GLUT2 expression by increasing concentrations (4-8 mg/mL) of oat β-glucan demonstrated a direct effect of the physical properties of oat β-glucan on glucose transport. These results affirmed oat β-glucan as a dietary agent for minimizing postprandial glucose and showed that modulating the activity of the key intestinal glucose transporters with oat β-glucan could be an effective way of lowering blood glucose levels in patients with diabetes. PMID:27188900

  4. Experimental lead poisoning and intestinal transport of glucose, amino acids, and sodium.

    PubMed

    Wapnir, R A; Exeni, R A; McVicar, M; Lipshitz, F

    1977-03-01

    Juvenile rats fed a diet containing 1% lead acetate for 7 weeks, in addition to an impaired growth rate and renal function derangements, suffered malabsorption of glucose and certain amino acids, as assessed by an in vivo perfusion technique. The reduction in glucose absorption ranged between 10% and 31% when the carbohydrate was pumped in concentrations of 2-80 mM. This alteration was compatible with a noncompetitive type of transport inhibition. The intestinal absorption of glycine, lysine, and phenylalanine were, respectively, decreased 22, 18, and 15% when these amino acids were present at 1 mM levels. Sodium transport was severely reduced (57.6 +/- 17.9 (SEM) vs. 124.2 +/- 17.4 muEq/min-cm) and intestinal mucosa (Na+-K+)-ATPase was concomitantly lower in the lead-intoxicated rats (186.4 +/- 19.0 vs 268.4 +/- 29.8 nmol P/min-mg protein). However, this enzyme was not altered in liver and kidney. Furthermore, intestinal mucosa fructose-1,6-diphosphatase, succinic dehydrogenase, pyruvate kinase, and tryptophan hydroxylase were not different in experimental and control animals. These studies substantiate the presence of functional and biochemical abnormalities in the intestinal mucosa of young rats when fed substantial amounts of a soluble lead salt. It is, therefore, reasonable to accept the possibility that physiologic damage occurs in tissues directly subjected to high and persistent levels of a toxic agents, as it occurs in other organs, underscoring the parallelism between transport mechanisms at the renal and intestinal levels.

  5. Modulation of ganciclovir intestinal absorption in presence of absorption enhancers.

    PubMed

    Shah, Pranav; Jogani, Viral; Mishra, Pushpa; Mishra, Anil Kumar; Bagchi, Tamishraha; Misra, Ambikanandan

    2007-10-01

    The purpose of this investigation was to study the influences of absorption enhancers in increasing oral bioavailability of Ganciclovir (GAN) by assessing the transepithelial permeation across cell monolayers in vitro and bioavailability in rats in vivo. The permeation of GAN across Caco-2 and MDCK cell monolayers in the absence/presence of dimethyl-beta-cyclodextrin (DMbetaCD), chitosan hydrochloride (CH), sodium lauryl sulphate (SLS), and their combinations was studied for a 2-h period. GAN was administered to rats in absence/presence of absorption enhancers and drug contents in plasma were estimated. We found that the apparent permeability coefficient (Papp) of GAN in absence of absorption enhancers (control) were 0.261 +/- 0.072 x 10(-6) and 0.486 +/- 0.063 x 10(-6) cm/s in Caco-2 and MDCK cell monolayers, respectively, whereas in the presence of DMbetaCD, CH, SLS, and their combinations, Papp of GAN increased by 5- to 25-fold and 7- to 33-fold as compared to control in Caco-2 and MDCK cell monolayers, respectively. However, in rats, the maximum enhancement in bioavailability of GAN during coadministration of these absorption enhancers was only fivefold compared to GAN control. To conclude, the absorption enhancers-DMbetaCD, CH, SLS, and their combinations demonstrated significant improvement in transepithelial permeation and bioavailability of GAN.

  6. GLUCOSE-INDUCED INTESTINAL VASODILATION VIA ADENOSINE A1 RECEPTORS REQUIRES NITRIC OXIDE BUT NOT K+ATP CHANNELS

    PubMed Central

    Matheson, Paul J.; Li, Na; Harris, Patrick D.; Zakaria, El Rasheid; Garrison, R. Neal

    2010-01-01

    INTRODUCTION Both nitric oxide (NO) and adenosine A1 receptor activation mediate microvascular vasodilation during intestinal glucose absorption. Our overall hypothesis is that ATP utilization during glucose absorption would increase adenosine metabolite release, which acts on adenosine A1 receptors to alter endothelial production of NO and/or activate ATP-dependent potassium channels (K+ATP) to dilate intestinal microvessels. METHODS Intravital videomicroscopy of the rat jejunum was used to record the vascular responses of inflow (termed 1A) arterioles and proximal (p3A) and distal (d3A) premucosal arterioles during exposure to isotonic glucose or mannitol solutions alone or in the presence of the selective nitric oxide synthase (NOS) inhibitor (L-NMMA), an adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX)), or a K+ATP channel inhibitor (glibenclamide). RESULTS As expected, glucose exposure caused rapid dilation of both p3A and d3A arterioles, while mannitol exposure had no effect on microvascular diameters. Adenosine A1 receptor blockade completely prevented glucose-induced dilation of the premucosal arterioles. NOS inhibition significantly blunted the glucose-induced vasodilation of the premucosal arterioles, but had little effect in the mannitol group. Simultaneous application of both the NOS inhibitor and the adenosine A1 receptor antagonist gave the same reduction in glucose-induced dilation of the premucosal arterioles as the adenosine A1 receptor antagonist alone. Blockade of K+ATP channels with glibenclamide did not attenuate glucose-induced vasodilation of the premucosal arterioles. CONCLUSIONS These data suggest that glucose-induced vasodilation of premucosal jejunal arterioles is mediated through adenosine A1 receptors, and NO at least partially mediates the adenosine A1 receptor-induced vasodilation. In addition, K+ATP channels are not involved in premucosal arteriolar vasodilation during intestinal glucose exposure. PMID

  7. Nonlinear intestinal absorption kinetics of cefuroxime axetil in rats.

    PubMed Central

    Ruiz-Balaguer, N; Nacher, A; Casabo, V G; Merino, M

    1997-01-01

    Cefuroxime is commercially available for parenteral administration as a sodium salt and for oral administration as cefuroxime axetil, the 1-(acetoxy)ethyl ester of the drug. Cefuroxime axetil is a prodrug of cefuroxime and has little, if any, antibacterial activity until hydrolyzed in vivo to cefuroxime. In this study, the absorption of cefuroxime axetil in the small intestines of anesthetized rats was investigated in situ, by perfusion at four concentrations (11.8, 5, 118 and 200 microM). Oral absorption of cefuroxime axetil can apparently be described as a specialized transport mechanism which obeys Michaelis-Menten kinetics. Parameters characterizing absorption of prodrug in free solution were obtained: maximum rate of absorption (Vmax) = 289.08 +/- 46.26 microM h-1, and Km = 162.77 +/- 31.17 microM. Cefuroxime axetil transport was significantly reduced in the presence of the enzymatic inhibitor sodium azide. On the other hand, the prodrug was metabolized in the gut wall through contact with membrane-bound enzymes in the brush border membrane before absorption occurred. This process reduces the prodrug fraction directly available for absorption. From a bioavailability point of view, therefore, the effects mentioned above can explain the variable and poor bioavailability following oral administration of cefuroxime axetil. Thus, future strategies in oral cefuroxime axetil absorption should focus on increasing the stability of the prodrug in the intestine by modifying the prodrug structure and/or targeting the compound to the absorption site. PMID:9021205

  8. Regulation of intestinal lipid absorption by clock genes.

    PubMed

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders. PMID:25033063

  9. Intestinal absorption and metabolism of homoursodeoxycholic acid in rats.

    PubMed

    Kuramoto, T; Moriwaki, S; Kawamoto, K; Hoshita, T

    1987-07-01

    Intestinal absorption, hepatic biotransformation and intestinal bacterial modification of the C25 homolog of ursodeoxycholic acid, homoursodeoxycholic acid, and its glycine conjugate, glycohomoursodeoxycholic acid, were studied in rats. Homoursodeoxycholic acid, like ursodeoxycholic acid, was efficiently absorbed from the intestine and rapidly excreted into the bile. Most (greater than 95%) of the absorbed homoursodeoxycholic acid was found to undergo beta-oxidation to form two C23 bile acids, norursodeoxycholic acid and nor-beta-muricholic acid during passage through the liver. Bacterial modification of homoursodeoxycholic acid was very similar to that of ursodeoxycholic acid. In the rat intestinal tract, glycohomoursodexycholic acid was deconjugated to form unconjugated homoursodeoxycholic acid which was then 7 beta-dehydroxylated to form homolithocholic acid.

  10. Regulation of intestinal lipid absorption by clock genes.

    PubMed

    Hussain, M Mahmood

    2014-01-01

    Plasma levels of triacylglycerols and diacylglycerols, the lipoproteins that transport them, and proteins involved in their absorption from the intestinal lumen fluctuate in a circadian manner. These changes are likely controlled by clock genes expressed in the intestine that are probably synchronized by neuronal and humoral signals from the suprachiasmatic nuclei, which constitute a master clock entrained by light signals from the eyes and from the environment, e.g., food availability. Acute changes in circadian rhythms--e.g., due to nonsynchronous work schedules or a transcontinental flight--may trigger intestinal discomfort. Chronic disruptions in circadian control mechanisms may predispose the individual to irritable bowel syndrome, gastroesophageal reflux disease, and peptic ulcer disease. A more detailed understanding of the molecular mechanisms underlying temporal changes in intestinal activity might allow us to identify novel targets for developing therapeutic approaches to these disorders.

  11. Intestinal absorption of serrapeptase (TSP) in rats.

    PubMed

    Moriya, N; Nakata, M; Nakamura, M; Takaoka, M; Iwasa, S; Kato, K; Kakinuma, A

    1994-08-01

    A sensitive sandwich enzyme immunoassay (e.i.a.) for serrapeptase (TSP), an orally available anti-inflammatory proteinase, was established using affinity-purified anti-TSP rabbit IgG and its Fab' fragment conjugated with horseradish peroxidase as the first and the second antibodies respectively. TSP in the plasma was determined by the e.i.a. after its oral administration (100 mg/kg) to rats. The peak concentration was observed between 30 min and 2 h after administration. TSP in the plasma samples was trapped on a microtitre plate coated with the affinity-purified anti-TSP rabbit IgG, and the hydrolysis of a synthetic fluorogenic substrate, butoxycarbonyl-Glu(benzyloxy)-Ala-Arg-4-methylcoumaryl-7-amide, by the trapped TSP was fluorometrically measured (proteinase assay). The values obtained by the e.i.a. and those obtained by the proteinase assay correlated well for various plasma samples. These results indicate that orally administered TSP was absorbed from the intestinal tract and transferred into the circulation in an enzymically active form.

  12. High paracellular nutrient absorption in intact bats is associated with high paracellular permeability in perfused intestinal segments.

    PubMed

    Brun, Antonio; Price, Edwin R; Gontero-Fourcade, Manuel N; Fernandez-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2014-09-15

    Water-soluble nutrients are absorbed by the small intestine via transcellular and paracellular mechanisms. Based on a few previous studies, the capacity for paracellular nutrient absorption seems greater in flying mammals than in nonflying mammals, but there has been little investigation of the mechanisms driving this difference. Therefore, we studied three species each of bats (Artibeus lituratus, Sturnira lilium and Carollia perspicillata) and nonflying mammals (Akodon montensis, Mus musculus and Rattus norvegicus). Using standard pharmacokinetic techniques in intact animals, we confirmed the greater paracellular nutrient absorption in the fliers, comparing one species in each group. Then we conducted in situ intestinal perfusions on individuals of all species. In both approaches, we measured the absorption of 3OMD-glucose, a nonmetabolizable glucose analog absorbed both paracellularly and transcellularly, as well as L-arabinose, which has no mediated transport. Fractional absorption of L-arabinose was three times higher in the bat (S. lilium: 1.2±0.24) than in the rodent (A. montensis: 0.35±0.04), whereas fractional absorption of 3OMD-glucose was complete in both species (1.46±0.4 and 0.97±0.12, respectively). In agreement, bats exhibited two to 12 times higher l-arabinose clearance per square centimeter nominal surface area than rodents in intestinal perfusions. Using L-arabinose, we estimated that the contribution of the paracellular pathway to total glucose absorption was higher in all three bats (109-137%) than in the rodents (13-39%). These findings contribute to an emerging picture that reliance on the paracellular pathway for nutrient absorption is much greater in bats relative to nonflying mammals and that this difference is driven by differences in intestinal permeability to nutrient-sized molecules.

  13. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    PubMed Central

    Ventrucci, Gislaine; de Mello, Maria Alice Roston; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones. PMID:11955290

  14. Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum.

    PubMed

    Coon, Steven D; Schwartz, John H; Rajendran, Vazhaikkurichi M; Jepeal, Lisa; Singh, Satish K

    2013-11-15

    Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H(+) gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H(+):Gly-Sar cotransport on the apical membranes of mouse jejunum. H(+):Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H(+):Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum.

  15. Regulation of Glucose Transporter Expression in Human Intestinal Caco-2 Cells following Exposure to an Anthocyanin-Rich Berry Extract

    PubMed Central

    Alzaid, Fawaz; Cheung, Hoi-Man; Preedy, Victor R.; Sharp, Paul A.

    2013-01-01

    Polyphenols contained within plant tissues are consumed in significant amounts in the human diet and are known to influence a number of biological processes. This study investigated the effects of an anthocyanin-rich berry-extract on glucose uptake by human intestinal Caco-2 cells. Acute exposure (15 min) to berry extract (0.125%, w/v) significantly decreased both sodium-dependent (Total uptake) and sodium-independent (facilitated uptake) 3H-D-glucose uptake. In longer-term studies, SGLT1 mRNA and GLUT2 mRNA expression were reduced significantly. Polyphenols are known to interact directly with glucose transporters to regulate the rate of glucose absorption. Our in vitro data support this mechanism and also suggest that berry flavonoids may modulate post-prandial glycaemia by decreasing glucose transporter expression. Further studies are warranted to investigate the longer term effects of berry flavonoids on the management of glycaemia in human volunteers. PMID:24236070

  16. Fluid absorption in the small intestine of healthy game birds and those infected with Spironucleus spp.

    PubMed

    Lloyd, S; Irvine, K L; Eves, S M; Gibson, J S

    2005-06-01

    Absorption of fluid by the small intestine of 4-week-old to 12-week-old farmed pheasants and partridges has been studied using an inverted sac technique. The mean rate of absorption was 54 +/- 4 (mean +/- standard error of the mean) microl/g dry tissue/min in pheasants and 49 +/- 3 microl/g dry tissue/min in partridges. Use of inhibitors and ion substitution suggested transepithelial transport driven by baso-lateral Na+/K+ pumps, in combination with mucosal Na+-coupled transporters, including Cl(-)-coupled transporters. Absorption was more than halved to 17 +/- 2 microl/g dry tissue/min (P < 0.001) in birds that were very heavily infected with Spironucleus spp. in their small intestine and showing a syndrome of diarrhoea, depression and loss of weight to severe emaciation. Birds carrying light to moderate levels of infection with Spironucleus had very variable rates of absorption that were statistically similar to the controls. Doubling the glucose concentration in the buffer to 40 mM significantly enhanced absorption.

  17. Role of Adrenergic Receptors in Glucose, Fructose and Galactose-Induced Increases in Intestinal Glucose Uptake in Dogs.

    PubMed

    Salman, T M; Alada, A R A; Oyebola, D D O

    2014-12-29

    The study investigated the role of adrenergic receptors in glucose, fructose-, and galactose- induced increases in intestinal glucose uptake. Experiments were carried out on fasted male anaesthetized Nigerian local dogs divided into seven groups (with five dogs per group). Group I dogs were administered normal saline and served as control. Dogs in groups II, III and IV were intravenously infused with glucose (1.1 mg/kg/min), fructose (1.1 mg/kg/min) and galactose (1.1 mg/kg/min) respectively. Another three groups, V, VI and VII were pretreated with prazosin (0.2mg/kg), propranolol (0.5mg/kg) or a combination of prazosin (0.2mg/kg) and propranolol (0.5mg/kg) followed by glucose infusion, frutose infusion or galactose infusion respectively. Through a midline laparatomy, the upper jejunum was cannulated for blood flow measurement and blood samples were obtained for measurement of glucose content of the arterial blood and venous blood from the upper jejunal segment. Glucose uptake was calculated as the product of jejunal blood flow and the difference between arterial and venous glucose levels (A-V glucose). The results showed that pretreatment of the animal with prazosin had no effect on glucose and galactose induced increases in glucose uptake. However, pretreatment with propranolol completely abolished glucose, fructose and galactose-induced increases in intestinal glucose uptake. Prazosin also significantly reduced galactose-induced increase in intestinal glucose uptake. The results suggest that the increases in intestinal glucose uptake induced by glucose and fructose are mediated mostly by beta adrenergic receptors while that of galactose is mediated by both alpha and beta adrenergic receptors.

  18. In vitro study of transporters involved in intestinal absorption of inorganic arsenic.

    PubMed

    Calatayud, Marta; Barrios, Julio A; Vélez, Dinoraz; Devesa, Vicenta

    2012-02-20

    Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs.

  19. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

    PubMed Central

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

    2015-01-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

  20. Glucose Absorption by the Bacillary Band of Trichuris muris

    PubMed Central

    Hansen, Michael; Nejsum, Peter; Mejer, Helena; Denwood, Matthew; Thamsborg, Stig M.

    2016-01-01

    Background A common characteristic of Trichuris spp. infections in humans and animals is the variable but low efficacy of single-dose benzimidazoles currently used in mass drug administration programmes against human trichuriasis. The bacillary band, a specialised morphological structure of Trichuris spp., as well as the unique partly intracellular habitat of adult Trichuris spp. may affect drug absorption and perhaps contribute to the low drug accumulation in the worm. However, the exact function of the bacillary band is still unknown. Methodology We studied the dependency of adult Trichuris muris on glucose and/or amino acids for survival in vitro and the absorptive function of the bacillary band. The viability of the worms was evaluated using a motility scale from 0 to 3, and the colorimetric assay Alamar Blue was utilised to measure the metabolic activity. The absorptive function of the bacillary band in living worms was explored using a fluorescent glucose analogue (6-NBDG) and confocal microscopy. To study the absorptive function of the bacillary band in relation to 6-NBDG, the oral uptake was minimised or excluded by sealing the oral cavity with glue and agarose. Principal Findings Glucose had a positive effect on both the motility (p < 0.001) and metabolic activity (p < 0.001) of T. muris in vitro, whereas this was not the case for amino acids. The 6-NBDG was observed in the pores of the bacillary band and within the stichocytes of the living worms, independent of oral sealing. Conclusions/Significance Trichuris muris is dependent on glucose for viability in vitro, and the bacillary band has an absorptive function in relation to 6-NBDG, which accumulates within the stichocytes. The absorptive function of the bacillary band calls for an exploration of its possible role in the uptake of anthelmintics, and as a potential anthelmintic target relevant for future drug development. PMID:27588682

  1. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption.

    PubMed

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P

    2015-09-01

    Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.

  2. The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-o-β-glucoside in Caco-2 cells.

    PubMed

    Zou, Tang-Bin; Feng, Dan; Song, Gang; Li, Hua-Wen; Tang, Huan-Wen; Ling, Wen-Hua

    2014-10-01

    Anthocyanins have multiple biological activities of benefit to human health. While a few studies have been conducted to evaluate the bioavailability of anthocyanins, the mechanisms of their absorption mechanism remain ill-defined. In the present study, we investigated the absorption mechanism of cyanidin-3-O-β-glucoside (Cy-3-G) in human intestinal epithelial (Caco-2) cells. Cy-3-G transport was assessed by measuring the absorptive and efflux direction. Inhibition studies were conducted using the pharmacological agents, phloridzin, an inhibitor of sodium-dependent glucose transporter 1 (SGLT1), or phloretin, an inhibitor of glucose transporter 2 (GLUT2). The results showed that phloridzin and phloretin significantly inhibited the absorption of Cy-3-G. In addition, Caco-2 cells transfected with small interfering RNA (siRNA) specific for SGLT1 or GLUT2 showed significantly decreased Cy-3-G absorption. These siRNA transfected cells also showed a significantly decreased rate of transport of Cy-3-G compared with the control group. These findings suggest that Cy-3-G absorption is dependent on the activities of SGLT1 and GLUT2 in the small intestine and that SGLT1 and GLUT2 could be a limiting step for the bioavailability of Cy-3-G. PMID:25314643

  3. Inhibition of intestinal absorption of phenylalanine by phenylalaninol.

    PubMed

    Shimomura, K; Fukushima, T; Danno, T; Matsumoto, K; Miyoshi, M

    1975-08-01

    Plasma phenylalanine and tyrosine levels in rats which had been orally administered L-phenylalaninol and L-phenylalanine were determined. Since these amino acid levels in rats administered L-phenylalanine solution containing L-phenylalaninol were significantly lower than those in rats administered L-phenylalanine alone. L-phenylalaninol appears to inhibit the intestinal absorption of L-phenylalanine. This effect was more potent than that of cycloleucine. L-phenylalaninol inhibited the phenylalanine transport of everted sacs. The Km value of L-phenylalanine was 3.44 X 10(-3) M and the Ki value of L-phenylalaninol was 7.69 M 10(-3) M from Lineweaver-Burk plots. From these two curves, it appeared that L-phenylalaninol may competitively inhibit the intestinal transport of L-phenylalanine. The effects of L-phenylalanine, L-phenylalaninol and cycloleucine on the urinary excretions of Na+ and K+ in rats were also examined. Potassium excretion which increased on oral administration of L-phenylalanine, was suppressed by the administration of L-phenylalaninol but not administration of cycloleucine. L-phenylalaninol alone enhanced Na+ excretion in urine. These results confirmed that L-phenylalaninol shows inhibitory effects as potent as those of cycloleucine on the intestinal absorption of L-phenylalanine. PMID:1228171

  4. Analysis of sequential events in intestinal absorption of folylpolyglutamate

    SciTech Connect

    Darcy-Vrillon, B.; Selhub, J.; Rosenberg, I.H.

    1988-09-01

    Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of ''natural'' folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.

  5. Contribution of solvent drag through intercellular junctions to absorption of nutrients by the small intestine of the rat.

    PubMed

    Pappenheimer, J R; Reiss, K Z

    1987-01-01

    The lumen of the small intestine in anesthetized rats was recirculated with 50 ml perfusion fluid containing normal salts, 25 mM glucose and low concentrations of hydrophilic solutes ranging in size from creatinine (mol wt 113) to Inulin (mol wt 5500). Ferrocyanide, a nontoxic, quadrupally charged anion was not absorbed; it could therefore be used as an osmotically active solute with reflection coefficient of 1.0 to adjust rates of fluid absorption, Jv, and to measure the coefficient of osmotic flow, Lp. The clearances from the perfusion fluid of all other test solutes were approximately proportional to Jv. From Lp and rates of clearances as a function of Jv and molecular size we estimate (a) the fraction of fluid absorption which passes paracellularly (approx. 50%), (b) coefficients of solvent drag of various solutes within intercellular junctions, (c) the equivalent pore radius of intercellular junctions (50 A) and their cross sectional area per unit path length (4.3 cm per cm length of intestine). Glucose absorption also varied as a function of Jv. From this relationship and the clearances of inert markers we calculate the rate of active transport of glucose, the amount of glucose carried paracellularly by solvent drag or back-diffusion at any given Jv and luminal glucose concentration and the concentration of glucose in the absorbate. The results indicate that solvent drag through paracellular channels is the principal route for intestinal transport of glucose or amino acids at physiological rates of fluid absorption and concentration. In the absence of luminal glucose the rate of fluid absorption and the clearances of all inert hydrophilic solutes were greatly reduced. It is proposed that Na-coupled transport of organic solutes from lumen to intercellular spaces provides the principal osmotic force for fluid absorption and triggers widening of intercellular junctions, thus promoting bulk absorption of nutrients by solvent drag. Further evidence for regulation

  6. VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption

    PubMed Central

    Nurmi, Harri; Saharinen, Pipsa; Zarkada, Georgia; Zheng, Wei; Robciuc, Marius R; Alitalo, Kari

    2015-01-01

    Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. The Vegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism. PMID:26459520

  7. Bile enhances glucose uptake, reduces permeability, and modulates effects of lectins, trypsin inhibitors and saponins on intestinal tissue.

    PubMed

    Bakke, Anne Marie; Chikwati, Elvis M; Venold, Fredrik F; Sahlmann, Christian; Holm, Halvor; Penn, Michael H; Oropeza-Moe, Marianne; Krogdahl, Åshild

    2014-02-01

    Antinutritional factors (ANFs) can disrupt digestive and other intestinal functions. ANFs in soybean meal (SBM) are implicated in proliferative and inflammatory responses in the intestine of various (functionally) monogastric animals, including Atlantic salmon (Salmo salar L.). The goal of the current study was to investigate the effect of ex vivo exposure of mid and distal intestinal tissue of salmon to soybean saponins (SAP), lectin (LEC) and Kunitz' trypsin inhibitor (KTI), singly and in combination, on epithelial function, as assessed by measuring in vitro glucose uptake pathways along a glucose concentration gradient. As solubilization of SAP in the calcium-containing Ringer's solution was problematic but resolved with the addition of a physiological concentration of bile collected from the gall bladder of salmon, an evaluation of bile effects became an added element. Results indicated that bile increased baseline glucose absorption and possibly transport, and also had a protective effect on the epithelial barrier, at least partially due to taurocholate. Compared to controls, tissues exposed to LEC+bile, KTI+bile and LEC+KTI+bile exhibited increased glucose uptake at the higher glucose concentrations, apparently due to markedly increased tissue permeability. Addition of SAP, however, attenuated the response, possibly by binding bile components. SAP+bile, also in combination with LEC and/or KTI, as well as LEC, KTI and LEC+KTI without bile often reduced transcellular glucose uptake pathways, while maintaining low tissue permeability. SAP+LEC+KTI+bile, LEC and KTI caused the most marked reductions. The distal intestine was more affected, reflecting the restriction of in vivo SBM-induced inflammatory changes to this region. PMID:24291392

  8. Lymph capillary pressure of rat intestinal villi during fluid absorption.

    PubMed

    Lee, J S

    1979-09-01

    A newly developed intestinal preparation is described for determining lymph capillary pressure (PL) in the villi in vivo and in vitro. Determination of PL provided an estimate of tissue fluid pressure in the villi. PL was related to the fluid absorption rate and increased by lymphatic obstruction. During fluid absorption from isotonic mucosal fluid, PL was 1.4 +/- 0.5 or 1.1 +/- 0.4 cmH2O determined in vivo or in vitro, respectively. Both pressures were essentially in the same range as that (0.7 +/- 0.3--1.3 +/- 0.5 cmH2O) in which the mucosal fluid was isotonic Na2SO4 solution or Na-free solutions from which little fluid absorption occurred. This range of pressures may be taken as the normal tissue fluid pressure in the villi. At a high rate of fluid absorption from hypotonic mucosal fluid, PL increased to 5.2 +/- 1.4 cmH2O and tissue fluid pressure was also similarly increased. It is concluded that the fluid absorptive process by the epithelium could not develop an appreciable hydrostatic pressure in the villus tissue space or in the lymphatics.

  9. In situ perfusion in rodents to explore intestinal drug absorption: challenges and opportunities.

    PubMed

    Stappaerts, Jef; Brouwers, Joachim; Annaert, Pieter; Augustijns, Patrick

    2015-01-30

    The in situ intestinal perfusion technique in rodents is a very important absorption model, not only because of its predictive value, but it is also very suitable to unravel the mechanisms underlying intestinal drug absorption. This literature overview covers a number of specific applications for which the in situ intestinal perfusion set-up can be applied in favor of established in vitro absorption tools, such as the Caco-2 cell model. Qualities including the expression of drug transporters and metabolizing enzymes relevant for human intestinal absorption and compatibility with complex solvent systems render the in situ technique the most designated absorption model to perform transporter-metabolism studies or to evaluate the intestinal absorption from biorelevant media. Over the years, the in situ intestinal perfusion model has exhibited an exceptional ability to adapt to the latest challenges in drug absorption profiling. For instance, the introduction of the mesenteric vein cannulation allows determining the appearance of compounds in the blood and is of great use, especially when evaluating the absorption of compounds undergoing intestinal metabolism. Moreover, the use of the closed loop intestinal perfusion set-up is interesting when compounds or perfusion media are scarce. Compatibility with emerging trends in pharmaceutical profiling, such as the use of knockout or transgenic animals, generates unparalleled possibilities to gain mechanistic insight into specific absorption processes. Notwithstanding the fact that the in situ experiments are technically challenging and relatively time-consuming, the model offers great opportunities to gain insight into the processes determining intestinal drug absorption.

  10. Absorption of thiamine and nicotinic acid in the rat intestine during fasting and immobilization stress

    NASA Technical Reports Server (NTRS)

    Kirilyuk, O. G.; Khmelevskiy, Y. V.

    1980-01-01

    By perfusion of isolated sections of intestine with a solution containing thiamine at a concentration of 3.1 micromole, it was established that thiamine absorption in animals fasted for 72 hours decreased by 28 percent, whereas absorption increased by 12 percent in rats after 24 hour immobilization. After immobilization, absorption of label in the intestinal mucosa increased. Na K ATPase activity in the intestinal mucosa decreased by 10 percent during fasting, and it increased with immobilization of the animals. Activity of Na K ATPase in the intestinal mucosa cells determined the absorption rate of thiamine and nicotinic acid at the level of vitamin transport through the plasma membranes of the enterocytes.

  11. [Study on intestinal absorption of ingredients from different compatibilities of Shaoyao Gancao decoction].

    PubMed

    Ma, Ting-ting; He, Rui; Gong, Mu-xin; Xu, Yong-song; Li, Jing; Zhai, Yong-song; Wan, Guang

    2015-11-01

    To study the compatible mechanisms and compatible proportion of Shaoyao Gancao decoction, the intestinal absorption of main ingredients in Shaoyao Gancao decoction SG11 (Baishao-Zhigancao 1: 1) , SG31 (Baishao-Zhigancao 3: 1), Baishao water decoction S and Zhigancao (G) were investigated and compared using in vitro everted intestinal sac model and in situ single pass intestinal perfusion (SPIP) model. The concentration of paeoniflorin (PF), liquiritin (LQ) and mono-ammonium glycyrrhizinate (GL) in test samples and samples of intestinal sac and intestinal perfusion was determined by HPLC. The intestinal absorptive amount and absorption parameters were calculated. Results showed that in the everted intestinal sac model, three ingredients could be absorbed by duodenum, jejunum and ileum, and the absorption in the jejunum was best for all 3 ingredients. The absorption rate of three ingredients in SG11 was significantly higher than that in single decoction (P < 0.05), but had no significant difference compared with SG31. In SPIP model, the absorption rate constant K(a), the apparent absorption coefficient P(app) and the absorption rate of three ingredients in SG11 were significantly higher than those in single decoction. Parameters of PF and GL in SG11 were significantly higher than those in SG31, but had no differences of LQ. It proved that the compatibility of Baishao and Zhigancao could improve the intestinal absorption of PF, LQ and GL. The absorption of each ingredient in SG11 was better than that in SG31.

  12. Dietary glutamine supplementation effects on amino acid metabolism, intestinal nutrient absorption capacity and antioxidant response of gilthead sea bream (Sparus aurata) juveniles.

    PubMed

    Coutinho, F; Castro, C; Rufino-Palomares, E; Ordóñez-Grande, B; Gallardo, M A; Oliva-Teles, A; Peres, H

    2016-01-01

    A study was undertaken to evaluate dietary glutamine supplementation effects on gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic and intestinal glutamine metabolism and oxidative status. For that purpose gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18% lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2% glutamine for 6weeks. Fish performance, body composition and intestinal nutrient absorption capacity were not affected by dietary glutamine levels. Hepatic and intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were also unaffected by dietary glutamine supplementation. In the intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower than in the liver, suggesting a higher use of glutamine for energy production by the intestine than by the liver. The liver showed higher catalase and glucose-6-phosphate dehydrogenase activities, while the intestine presented higher glutathione peroxidase and glutathione reductase activities and oxidised glutathione content, which seems to reveal a higher glutathione dependency of the intestinal antioxidant response. Total and reduced glutathione contents in liver and intestine and superoxide dismutase activity in the intestine were enhanced by dietary glutamine, though lipid peroxidation values were not affected. Overall, differences between liver and intestine glutamine metabolism and antioxidant response were identified and the potential of dietary glutamine supplementation to gilthead sea bream's antioxidant response was elucidated.

  13. Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice.

    PubMed

    Yu, Qin; Liu, Xuemei; Liu, Yongjian; Riederer, Brigitte; Li, Taolang; Tian, De-An; Tuo, Biguang; Shull, Gary; Seidler, Ursula

    2016-08-01

    The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion. In order to better understand its physiological function in the intestine, isolated mucosae in miniaturized Ussing chambers and microdissected intestinal villi or crypts loaded with the fluorescent pH-indicator BCECF were studied from the duodenum, jejunum, and colon of 14- to 17-days-old slc4a4-deficient (KO) and WT mice. NBCe1 was active in the basal state in all intestinal segments under study, most likely to compensate for acid loads imposed upon the enterocytes. Upregulation of other basolateral base uptake mechanism occurs, but in a segment-specific fashion. Loss of NBCe1 resulted in severely impaired Cl(-) and fluid secretory response, but not HCO3 (-) secretory response to agonist stimulation. In addition, NBCe1 was found to be active during transport processes that load the surface enterocytes with acid, such as Slc26a3 (DRA)-mediated luminal Cl(-)/HCO3 (-) exchange or PEPT1-mediated H(+)/dipeptide uptake. Possibly because of the high energy demand for hyperventilation in conjunction with the fluid secretory and nutrient absorptive defects and the relative scarcity of compensatory mechanisms, NBCe1-deficient mice developed progressive jejunal failure, worsening of metabolic acidosis, and death in the third week of life. Our data suggest that the electrogenic influx of base via NBCe1 maintains enterocyte anion homeostasis and pHi control. Its loss impairs small intestinal Cl(-) and fluid secretion as well as the neutralization of acid loads imposed on the enterocytes during nutrient and electrolyte absorption. PMID:27228994

  14. Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice.

    PubMed

    Yu, Qin; Liu, Xuemei; Liu, Yongjian; Riederer, Brigitte; Li, Taolang; Tian, De-An; Tuo, Biguang; Shull, Gary; Seidler, Ursula

    2016-08-01

    The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion. In order to better understand its physiological function in the intestine, isolated mucosae in miniaturized Ussing chambers and microdissected intestinal villi or crypts loaded with the fluorescent pH-indicator BCECF were studied from the duodenum, jejunum, and colon of 14- to 17-days-old slc4a4-deficient (KO) and WT mice. NBCe1 was active in the basal state in all intestinal segments under study, most likely to compensate for acid loads imposed upon the enterocytes. Upregulation of other basolateral base uptake mechanism occurs, but in a segment-specific fashion. Loss of NBCe1 resulted in severely impaired Cl(-) and fluid secretory response, but not HCO3 (-) secretory response to agonist stimulation. In addition, NBCe1 was found to be active during transport processes that load the surface enterocytes with acid, such as Slc26a3 (DRA)-mediated luminal Cl(-)/HCO3 (-) exchange or PEPT1-mediated H(+)/dipeptide uptake. Possibly because of the high energy demand for hyperventilation in conjunction with the fluid secretory and nutrient absorptive defects and the relative scarcity of compensatory mechanisms, NBCe1-deficient mice developed progressive jejunal failure, worsening of metabolic acidosis, and death in the third week of life. Our data suggest that the electrogenic influx of base via NBCe1 maintains enterocyte anion homeostasis and pHi control. Its loss impairs small intestinal Cl(-) and fluid secretion as well as the neutralization of acid loads imposed on the enterocytes during nutrient and electrolyte absorption.

  15. Intestinal Water Absorption Varies with Expected Dietary Water Load among Bats but Does Not Drive Paracellular Nutrient Absorption.

    PubMed

    Price, Edwin R; Brun, Antonio; Gontero-Fourcade, Manuel; Fernández-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2015-01-01

    Rapid absorption and elimination of dietary water should be particularly important to flying species and were predicted to vary with the water content of the natural diet. Additionally, high water absorption capacity was predicted to be associated with high paracellular nutrient absorption due to solvent drag. We compared the water absorption rates of sanguivorous, nectarivorous, frugivorous, and insectivorous bats in intestinal luminal perfusions. High water absorption rates were associated with high expected dietary water load but were not highly correlated with previously measured rates of (paracellular) arabinose clearance. In conjunction with these tests, we measured water absorption and the paracellular absorption of nutrients in the intestine and stomach of vampire bats using luminal perfusions to test the hypothesis that the unique elongated vampire stomach is a critical site of water absorption. Vampire bats' gastric water absorption was high compared to mice but not compared to their intestines. We therefore conclude that (1) dietary water content has influenced the evolution of intestinal water absorption capacity in bats, (2) solvent drag is not the only driver of paracellular nutrient absorption, and (3) the vampire stomach is a capable but not critical location for water absorption.

  16. Intestinal Water Absorption Varies with Expected Dietary Water Load among Bats but Does Not Drive Paracellular Nutrient Absorption.

    PubMed

    Price, Edwin R; Brun, Antonio; Gontero-Fourcade, Manuel; Fernández-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2015-01-01

    Rapid absorption and elimination of dietary water should be particularly important to flying species and were predicted to vary with the water content of the natural diet. Additionally, high water absorption capacity was predicted to be associated with high paracellular nutrient absorption due to solvent drag. We compared the water absorption rates of sanguivorous, nectarivorous, frugivorous, and insectivorous bats in intestinal luminal perfusions. High water absorption rates were associated with high expected dietary water load but were not highly correlated with previously measured rates of (paracellular) arabinose clearance. In conjunction with these tests, we measured water absorption and the paracellular absorption of nutrients in the intestine and stomach of vampire bats using luminal perfusions to test the hypothesis that the unique elongated vampire stomach is a critical site of water absorption. Vampire bats' gastric water absorption was high compared to mice but not compared to their intestines. We therefore conclude that (1) dietary water content has influenced the evolution of intestinal water absorption capacity in bats, (2) solvent drag is not the only driver of paracellular nutrient absorption, and (3) the vampire stomach is a capable but not critical location for water absorption. PMID:26658415

  17. Increased Intestinal Absorption of Genistein by Coadministering Verapamil in Rats.

    PubMed

    Xie, Baogang; Wang, Huiyun; Zou, Huiqin; Liu, Yalan; Kong, Xiangyu; Fang, Xiuzhong

    2016-10-01

    Combination of genistein (GT) and verapamil, a P-glycoprotein (P-gp) inhibitor, can increase GT absorption in situ perfusion technology in rat. To date, little information is yet available about the effect of verapamil on oral absorption of GT in vivo. In this study, a simple and reproducible HPLC-UV method was developed and validated for determination of total GT in rat plasma. Based on this, a pharmacokinetic experiment was designed to characterize biopharmaceutical properties of GT with or without coadministration of verapamil (10.0, 20.0, 30.0 mg/kg) in rats. The coadministration of verapamil (30.0 mg/kg) with GT caused a significant increase of the maximum GT plasma concentration (1.31-fold vs. GT, P < 0.05) and area under the curve (1.39-fold vs. GT, P < 0.05). Our data show that verapamil would increase intestinal absorption of GT in rat, suggesting there is some drug-nutrition interaction between verapamil and GT. PMID:27604118

  18. Absorption enhancing effects of chitosan oligomers on the intestinal absorption of low molecular weight heparin in rats.

    PubMed

    Zhang, Hailong; Mi, Jie; Huo, Yayu; Huang, Xiaoyan; Xing, Jianfeng; Yamamoto, Akira; Gao, Yang

    2014-05-15

    Absorption enhancing effects of chitosan oligomers with different type and varying concentration on the intestinal absorption of low molecular weight heparin (LMWH) were examined by an in situ closed loop method in different intestinal sections of rats. Chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the highest absorption enhancing ability both in the small intestine and large intestine. The membrane toxicities of chitosan oligomers were evaluated by morphological observation and determining the biological markers including amount of protein and activity of lactate dehydrogenase (LDH) released from intestinal epithelium cells. There was no obvious change both in levels of protein and LDH and morphology in the intestinal membrane between control and various chitosan oligomers groups, suggesting that chitosan oligomers did not induce any significant membrane damage to the intestinal epithelium. In addition, zeta potentials became less negative and amount of free LMWH gradually decreased when various chitosan oligomers were added to LMWH solution, revealing that electrostatic interaction between positively charged chitosan oligomers and negative LMWH was included in the absorption enhancing mechanism of chitosan oligomers. In conclusion, chitosan oligomers, especially chitosan hexamer, are safe and efficient absorption enhancers and can be used promisingly to improve oral absorption of LMWH.

  19. Extra-intestinal calcium handling contributes to normal serum calcium levels when intestinal calcium absorption is suboptimal.

    PubMed

    Lieben, Liesbet; Verlinden, Lieve; Masuyama, Ritsuko; Torrekens, Sophie; Moermans, Karen; Schoonjans, Luc; Carmeliet, Peter; Carmeliet, Geert

    2015-12-01

    The active form of vitamin D, 1,25(OH)2D, is a crucial regulator of calcium homeostasis, especially through stimulation of intestinal calcium transport. Lack of intestinal vitamin D receptor (VDR) signaling does however not result in hypocalcemia, because the increased 1,25(OH)2D levels stimulate calcium handling in extra-intestinal tissues. Systemic VDR deficiency, on the other hand, results in hypocalcemia because calcium handling is impaired not only in the intestine, but also in kidney and bone. It remains however unclear whether low intestinal VDR activity, as observed during aging, is sufficient for intestinal calcium transport and for mineral and bone homeostasis. To this end, we generated mice that expressed the Vdr exclusively in the gut, but at reduced levels. We found that ~15% of intestinal VDR expression greatly prevented the Vdr null phenotype in young-adult mice, including the severe hypocalcemia. Serum calcium levels were, however, in the low-normal range, which may be due to the suboptimal intestinal calcium absorption, renal calcium loss, insufficient increase in bone resorption and normal calcium incorporation in the bone matrix. In conclusion, our results indicate that low intestinal VDR levels improve intestinal calcium absorption compared to Vdr null mice, but also show that 1,25(OH)2D-mediated fine-tuning of renal calcium reabsorption and bone mineralization and resorption is required to maintain fully normal serum calcium levels.

  20. Time dependent changes in the intestinal Ca²⁺ absorption in rats with type I diabetes mellitus are associated with alterations in the intestinal redox state.

    PubMed

    Rivoira, María; Rodríguez, Valeria; López, María Peralta; Tolosa de Talamoni, Nori

    2015-03-01

    The aim was to determine the intestinal Ca²⁺ absorption in type I diabetic rats after different times of STZ induction, as well as the gene and protein expression of molecules involved in both the transcellular and paracellular Ca²⁺ pathways. The redox state and the antioxidant enzymes of the enterocytes were also evaluated in duodenum from either diabetic or insulin-treated diabetic rats as compared to control rats. Male Wistar rats (150-200 g) were divided into two groups: 1) controls and 2) STZ-induced diabetic rats (60 mg/kg b.w.). A group of diabetic rats received insulin for five days. The insulin was adjusted daily to maintain a normal blood glucose level. Five 5 d after STZ injection, there was a reduction in the intestinal Ca²⁺ absorption, which was maintained for 30 d and disappeared at 60 d. Similar changes occurred in the GSH and (˙)O(2)(-) levels. The protein expression of molecules involved in the transcellular pathway increased at 5 and 30 d returning to control values at 60 d. Their mRNA levels declined considerably at 60 d. The gene and protein expression of claudin 2 was upregulated at 30 d. Catalase activity increased at 5 and 30 d normalizing at 60 d. To conclude, type I D.m. inhibits the intestinal Ca²⁺ absorption, which is transient leading to a time dependent adaptation and returning the absorptive process to normal values. The inhibition is accompanied by oxidative stress. When insulin is administered, the duodenal redox state returns to control values and the intestinal Ca²⁺ absorption normalizes.

  1. Intestinal absorption of aspartame decomposition products in adult rats.

    PubMed

    Lipton, W E; Li, Y N; Younoszai, M K; Stegink, L D

    1991-12-01

    The dipeptide sweetener aspartame (N-L-alpha-aspartyl-L-phenylalanine, 1-methyl ester; alpha-APM) is relatively stable in dry powder form. However, when exposed to elevated temperature, extremes of pH and/or moisture, alpha-APM is converted into a variety of products. In aqueous solution alpha-APM decomposes to yield methanol, two isomeric forms of L-aspartyl-L-phenylalanine (Asp-Phe) [alpha-Asp-Phe and beta-Asp-Phe], and APM's diketopiperazine cyclo-Asp-Phe. Depending on beverage storage conditions, individuals drinking alpha-APM-sweetened beverages may consume small quantities of these three compounds. Relatively little has been published about the metabolism of beta-Asp-Phe and cyclo-Asp-Phe. We compared the absorption and metabolism of alpha-Asp-Phe, beta-Asp-Phe, and cyclo-Asp-Phe with that of L-phenylalanine (Phe) in adult rats. Steady-state perfusion studies of rat jejunum indicated rapid carrier-assisted uptake of Phe and alpha-Asp-Phe, but only slow passive diffusion of beta-Asp-Phe and cyclo-Asp-Phe from the lumen. Homogenates of rat intestinal mucosa, liver, and cecal contents, as well as homogenates of pure cultures of Escherichia coli B, catalyzed the hydrolysis of alpha-Asp-Phe, but not cyclo-Asp-Phe. Homogenates of E coli and rat cecal contents, but not homogenates of rat liver or intestinal mucosa catalyzed the hydrolysis of beta-Asp-Phe.

  2. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish.

    PubMed

    Semova, Ivana; Carten, Juliana D; Stombaugh, Jesse; Mackey, Lantz C; Knight, Rob; Farber, Steven A; Rawls, John F

    2012-09-13

    Regulation of intestinal dietary fat absorption is critical to maintaining energy balance. While intestinal microbiota clearly impact the host's energy balance, their role in intestinal absorption and extraintestinal metabolism of dietary fat is less clear. Using in vivo imaging of fluorescent fatty acid (FA) analogs delivered to gnotobiotic zebrafish hosts, we reveal that microbiota stimulate FA uptake and lipid droplet (LD) formation in the intestinal epithelium and liver. Microbiota increase epithelial LD number in a diet-dependent manner. The presence of food led to the intestinal enrichment of bacteria from the phylum Firmicutes. Diet-enriched Firmicutes and their products were sufficient to increase epithelial LD number, whereas LD size was increased by other bacterial types. Thus, different members of the intestinal microbiota promote FA absorption via distinct mechanisms. Diet-induced alterations in microbiota composition might influence fat absorption, providing mechanistic insight into how microbiota-diet interactions regulate host energy balance.

  3. L-arginine in low concentration improves rat intestinal water and sodium absorption from oral rehydration solutions.

    PubMed Central

    Wapnir, R A; Wingertzahn, M A; Teichberg, S

    1997-01-01

    BACKGROUND: The nitric oxide (NO) precursor L-arginine has been shown to produce variable effects on intestinal absorptive function, including ion transport. AIMS: To determine whether there is an optimal concentration of L-arginine, promoting proabsorptive effects from oral rehydration solutions (ORS) with 90 or 60 mM sodium. SUBJECTS AND METHODS: In vivo perfusion of rat jejunum with determination of net water absorption, unidirectional fluid exchanges, sodium and calcium transport, and glucose absorption. RESULTS: L-Arginine (1 mM) added to the 90 mM sodium ORS increased intestinal absorption of both sodium and water. Higher concentrations of L-arginine (2 to 10 mM) lacked this stimulatory effect. At 20 mM, L-arginine decreased sodium absorption below baseline. With a 60 mM sodium ORS, 2 mM L-arginine had a maximal fluid and electrolyte proabsorptive effect. At 20 mM L-arginine, net water absorption was indistinguishable from that obtained in the absence of L-arginine, and lower than with 2 mM L-arginine. Sodium absorption remained raised above baseline in perfusions with 10 and 20 mM L-arginine. Morphologically, villi from perfusions with increased absorption showed a large expansion of intercellular and lamina propria intercellular spaces. CONCLUSIONS: Low concentrations of L-arginine seem to stimulate water and electrolyte absorption by the small intestine. This effect is consistent with NO induced vasodilation, may be vaso-constrictive and thereby reverse fluid and electrolyte transport. Images PMID:9203937

  4. Solvent drag effect in drug intestinal absorption. II. Studies on drug absorption clearance and water influx.

    PubMed

    Karino, A; Hayashi, M; Awazu, S; Hanano, M

    1982-09-01

    In order to study the solvent drag effect, it was shown that back flux of absorbed drug from blood to intestinal lumen can be ignored but the back flux of water cannot. Then, apparent water influx was calculated as a new measure of solvent drag based on the model in which the back flux of D2O from blood to lumen was considered during absorption. Consequently, the correlation between drug absorption clearance (CLdrug) and apparent water influx was highly significant for benzoic acid, salicylic acid, p-hydroxybenzoic acid, antipyrine, cephalexin (CEX) and cefroxadine (CXD), resulting the high solvent drag effects were detected. The mean values of the slopes in the regression lines of CLdrug versus apparent water influx, i.e., sieving coefficients, were smaller than one for benzoic acid and salicylic acid, but the values were not significantly different from one. The sieving coefficients of the other drugs were significantly smaller than one. From these results, the molecular size dependence in the reflection from the intestinal membrane during absorption was clearly shown. And the intercepts of the regression lines including diffusive permeabilities were found to be significantly different from zero in CEX and CXD. On the basis of the sieving coefficients and intercept values obtained in such ways, the appropriateness of this model was discussed.

  5. Intestinal calcium absorption in rats is stimulated by dietary lactulose and other resistant sugars.

    PubMed

    Brommage, R; Binacua, C; Antille, S; Carrié, A L

    1993-12-01

    Lactulose is a disaccharide analogue of lactose that is resistant to metabolism in the small intestine but not in the large intestine. The effects of lactulose and other sugars on intestinal Ca absorption were determined from the decrease in the 47Ca:47 Sc ratio between diet and feces after feeding male rats diets containing these sugars during a single night. Dietary lactulose was more potent than lactose in stimulating Ca absorption and was effective between 5 and 38 wk of age. The component sugars of lactulose, galactose and fructose, did not influence Ca absorption when provided together at concentrations equimolar to that of lactulose. The stimulation of Ca absorption by dietary lactulose increased as dietary Ca concentration was raised and was not influenced by prior injections of calcitriol. Lactulose must be present in the same meal as Ca to stimulate Ca absorption, but this stimulation was lost if the rats were fed lactulose continuously for 2 or 7 d prior to the test diet. Other sugars thought to be poorly absorbed in the small intestine (xylitol, lactobionate, arabinose, raffinose, pyroglutamate, sorbitol, gluconate and raftilose) stimulated Ca absorption to an identical extent as lactulose. Cecectomy did not influence the enhancement of Ca absorption by lactulose. These results indicate that sugars resistant to metabolism and absorption in the small intestine but not the large intestine stimulate Ca absorption in the small intestine.

  6. Intestinal absorption of colostral lymphoid cells in newborn piglets.

    PubMed

    Tuboly, S; Bernáth, S; Glávits, R; Medveczky, I

    1988-12-01

    Intestinal absorption of colostral lymphoid cells was studied in 23 piglets of four sows (sows A, B, C and D). From the colostrum and blood of the sows the lymphoid cells were isolated with Ficoll-Paque and labelled with technetium (Na99mTcO4). In the 7th hour after birth, 5-ml volumes of the cell suspensions were injected, following laparotomy, directly into the stomach (piglets of sow A) or into the jejunum (piglets of sow B), whereas piglets of sows C and D received the suspensions through a naso-oesophageal tube. Cryostat sections of duodenum, jejunum and lymph node samples of piglets killed by bleeding 8 h after the treatment were examined by autoradiography. It was found that lymphoid cells present in the colostrum of a piglet's own mother were absorbed from the digestive tract and, via the lymphatic vessels, were transported to the mesenteric lymph nodes. Electron microscopy revealed that absorption took place intercellularly. Colostral cells of sows other than a piglet's own mother were observed only in the epithelial layer of the mucous membrane. The lymphoid cells isolated from the sows' blood and heat-treated colostral lymphoid cells were not absorbed. The results indicate that in the pig, an animal having an epitheliochorial placenta, the colostral lymphoid cells are absorbed from the digestive tract and, hence, they can confer an active cellular immunity on the newborn piglets.

  7. [Study on intestinal absorption features of oligosaccharides in Morinda officinalis How. with sigle-pass perfusion].

    PubMed

    Deng, Shao-Dong; Zhang, Peng; Lin, Li; Xiao, Feng-Xia; Lin, Jing-Ran

    2015-01-01

    To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum, jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results, all of the five oligosaccharides were absorbed in the whole intestine, and their absorption rates were affected by the pH of the perfusion solution, drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments, without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.

  8. [Recent knowledge about intestinal absorption and cleavage of carotenoids].

    PubMed

    Borel, P; Drai, J; Faure, H; Fayol, V; Galabert, C; Laromiguière, M; Le Moël, G

    2005-01-01

    Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the

  9. [Study on intestinal absorption of formononetin in Millettia nitita var. hirsutissima in rats].

    PubMed

    Liu, Ya-Li; Xiong, Xian-Bing; Su, Dan; Song, Yong-Gui; Zhang, Ling; Yang, Shi-Lin

    2013-10-01

    To use the single-pass intestine perfusion (SPIP) model and HPLC to determine the concentration of formononetin, the effect of quality concentrations of formononetin, different intestinal segments and P-glycoprotein inhibitor on intestinal absorption of formononetin, in order to observe the intestinal absorption mechanism of formononetin from Millettia nitita var. hirsutissima in rats. The experimental results showed that the qulaity concentration of formononetin in the perfusate had no significant effect on the absorption rate constant (K(a)) and the apparent absorption coefficient (P(app)); K(a) and P(app) of formononetin in duodenum, jejunum and ileum showed no significant difference. However, K(a) was significantly higher than that in colon (P < 0.05), with significant difference between that in intestinum tenue and colon. P-glycoprotein inhibitor verapamil showed significant difference in K(a) and P(app) in intestinal segments (P < 0.05). This indicated that the absorption mechanism of formononein in rat intestinal tracts passive diffusion, without any saturated absorption. Formononein is absorbed well in all intestines. Their absorption windows were mainly concentrated in the intestinum tenue, without specific absorption sites. Formononein may be the substrate of P-glycoprotein. PMID:24490575

  10. Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.

    PubMed

    Aoshima, Naoya; Fujie, Yoshiko; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

    2014-01-01

    Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme--UDP-glucuronosyltransferase (UGT) 1A1--to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined in the liver and small intestine of neonatal hUGT1 mice that were orally treated with glucose. In the hUGT1 mice, glucose induced UGT1A1 in the small intestine, while it did not affect the expression of UGT1A1 in the liver. UGT1A1 was also induced in the human intestinal Caco-2 cells when the cells were cultured in the presence of glucose. Luciferase assays demonstrated that not only the proximal region (-1300/-7) of the UGT1A1 promoter, but also distal region (-6500/-4050) were responsible for the induction of UGT1A1 in the intestinal cells. Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding. PMID:25209391

  11. [Absorption of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by everted intestinal sac method].

    PubMed

    Zhao, Jie; Xu, Xue-lin; Yi, Hong; Zhang, Hong-min; Liu, Xiao-qian; Zhu, Jing-jing; Wang, Zhi-min

    2015-08-01

    To study the absorptive characteristics of aqueous extracts from Salviae Miltiorrhizae Radix et Rhizoma by in vitro rat everted intestinal sac model. Three representative ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et Rhizome--protocatechuic aldehyde (PAL), posmarinic acid (RA) and salvianolic acid B (SAB), were selected as the study objects. An UPLC method was established to determine and measure their cumulative absorption amount, in order to explain the absorption characteristics of ingredients in different intestinal sections. According to the experimental result, RA and SAB showed the passive absorption in ileum, which conformed to the first-order absorption rate; with low and medium doses, they showed a zero-order absorption rate in jejunum, which was reflected in the coexistence of both positive and passive absorptions; PAL showed a passive absorption manner both in ileum and jejunum. According to the experiment for absorption in different intestinal sections, RA and SAB were mainly absorbed in jejunum, while PAL was absorbed mainly in ileum. All of the three ingredients in aqueous extracts from Salviae Miltiorrhizae Radix et rhizome--PAL, RA and SAB could be absorbed in intestines, but with differences in the absorption rate and mechanism, which indicated that the intestinal absorption of aqueous extracts from Salviae Miltiorrhizae Radix et rhizome was selectivity, instead of a simple semi-permeable membrane penetration process.

  12. Aboral changes in D-glucose transport by human intestinal brush-border membrane vesicles.

    PubMed Central

    Bluett, M K; Abumrad, N N; Arab, N; Ghishan, F K

    1986-01-01

    D-Glucose transport was investigated in isolated brush-border membrane vesicles from human small intestine. Characteristics of D-glucose transport from the jejunum were compared with that in the mid and terminal ileum. Jejunal and mid-ileal D-glucose transport was Na+-dependent and electrogenic. The transient overshoot of jejunal D-glucose transport was significantly greater than corresponding values in mid-ileum. The terminal ileum did not exhibit Na+-dependent D-glucose transport, but did exhibit Na+-dependent taurocholate transport. Na+-glucose co-transport activity as measured by tracer-exchange experiments was greatest in the jejunum, and diminished aborally. We conclude that D-glucose transport in man is Na+-dependent and electrogenic in the proximal intestine and directly related to the activity of D-glucose-Na+ transporters present in the brush-border membranes. D-Glucose transport in the terminal ileum resembles colonic transport of D-glucose. PMID:3800877

  13. Molecular mechanisms of glucose-stimulated GLP-1 secretion from perfused rat small intestine.

    PubMed

    Kuhre, Rune E; Frost, Charlotte R; Svendsen, Berit; Holst, Jens J

    2015-02-01

    Glucose is an important stimulus for glucagon-like peptide 1 (GLP-1) secretion, but the mechanisms of secretion have not been investigated in integrated physiological models. We studied glucose-stimulated GLP-1 secretion from isolated perfused rat small intestine. Luminal glucose (5% and 20% w/v) stimulated the secretion dose dependently, but vascular glucose was without significant effect at 5, 10, 15, and 25 mmol/L. GLP-1 stimulation by luminal glucose (20%) secretion was blocked by the voltage-gated Ca channel inhibitor, nifedipine, or by hyperpolarization with diazoxide. Luminal administration (20%) of the nonmetabolizable sodium-glucose transporter 1 (SGLT1) substrate, methyl-α-D-glucopyranoside (α-MGP), stimulated release, whereas the SGLT1 inhibitor phloridzin (luminally) abolished responses to α-MGP and glucose. Furthermore, in the absence of luminal NaCl, luminal glucose (20%) did not stimulate a response. Luminal glucose-stimulated GLP-1 secretion was also sensitive to luminal GLUT2 inhibition (phloretin), but in contrast to SGLT1 inhibition, phloretin did not eliminate the response, and luminal glucose (20%) stimulated larger GLP-1 responses than luminal α-MGP in matched concentrations. Glucose transported by GLUT2 may act after metabolization, closing KATP channels similar to sulfonylureas, which also stimulated secretion. Our data indicate that SGLT1 activity is the driving force for glucose-stimulated GLP-1 secretion and that KATP-channel closure is required to stimulate a full-blown glucose-induced response.

  14. Intestinal absorption and tissue distribution of ( sup 14 C)pyrroloquinoline quinone in mice

    SciTech Connect

    Smidt, C.R.; Unkefer, C.J.; Houck, D.R.; Rucker, R.B. )

    1991-05-01

    Pyrroloquinoline quinone (PQQ) functions as a cofactor for prokaryotic oxidoreductases, such as methanol dehydrogenase and membrane-bound glucose dehydrogenase. In animals fed chemically defined diets, PQQ improves reproductive outcome and neonatal growth. Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion. About 28 micrograms of PQQ (0.42 microCi/mumol), labeled with {sup 14}C derived from L-tyrosine, was administered orally to Swiss-Webster mice (18-20 g) to estimate absorption. PQQ was readily absorbed (62%, range 19-89%) in the lower intestine, and was excreted by the kidneys (81% of the absorbed dose) within 24 hr. The only tissues that retained significant amounts of ({sup 14}C)PQQ at 24 hr were skin and kidney. For kidney, it was assumed that retention of ({sup 14}C)PQQ represented primarily PQQ destined for excretion. For skin, the concentration of ({sup 14}C)PQQ increased from 0.3% of the absorbed dose at 6 hr to 1.3% at 24 hr. Furthermore, most of the ({sup 14}C)PQQ in blood (greater than 95%) was associated with the blood cell fraction, rather than plasma.

  15. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

    PubMed Central

    Ferrebee, Courtney B.; Dawson, Paul A.

    2015-01-01

    The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5). PMID:26579438

  16. Pinoresinol of olive oil decreases vitamin D intestinal absorption.

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Tagliaferri, Camille; Lebecque, Patrice; Georgé, Stéphane; Wittrant, Yohann; Coxam, Véronique; Amiot, Marie-Josèphe; Reboul, Emmanuelle

    2016-09-01

    Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D.

  17. Characterization of ovalbumin absorption pathways in the rat intestine, including the effects of aspirin.

    PubMed

    Yokooji, Tomoharu; Nouma, Hitomi; Matsuo, Hiroaki

    2014-01-01

    Ingested proteins are absorbed from the intestinal lumen via the paracellular and/or transcellular pathways, depending on their physicochemical properties. In this study, we investigated the absorption pathway(s) of ovalbumin (OVA), an egg white-allergen, as well as the mechanisms of aspirin-facilitated OVA absorption in rats. In situ intestinal re-circulating perfusion experiments showed that the absorption rate of fluorescein isothiocyanate (FITC)-labeled OVA in the distal intestine was higher than that for a marker of non-specific absorption, FITC-dextran (FD-40), and that colchicine, a general endocytosis inhibitor, suppressed OVA absorption. In the distal intestine, bafiromycin A1 and phenylarsine oxide inhibited the OVA absorption rate, whereas mehyl-β-cyclodextrin exerted no significant effects. Thus, OVA is preferentially absorbed from the distal intestine via the paracellular and receptor- and clathrin-mediated endocytic pathways. Furthermore, aspirin increased OVA absorption in the presence or absence of colchicine, indicating that aspirin facilitated OVA absorption by inducing intestinal barrier disruption and paracellular permeability.

  18. Update: The Digestion and Absorption of Carbohydrate and Protein: Role of the Small Intestine.

    ERIC Educational Resources Information Center

    Leese, H. J.

    1984-01-01

    Discusses the role of the small intestine in the digestion and absorption of carbohydrates and proteins. Indicates as outdated the view that these materials must be broken down to monomeric units before absorption and that the gut secretes a mixture of digestive juices which brings about absorption. (JN)

  19. Limited fat absorption in the large intestine of mice. A morphological study.

    PubMed

    Snipes, R L

    1977-01-01

    A limited fat-absorbing ability of the epithelial cells in the cecum and colon of mice was demonstrated light- and electron-microscopically. After injection of predigested donor fat into ligated segments of the large intestine and after massive gastric intubation of fat, fat droplets, predominantly of extremely large diameter, were visible in the cecum and colon. Comparison with fat absorption in the proximal and distal small intestine was undertaken. The large intestine, similar to the distal small intestine, is capable of absorbing lipids; however, the subsequent processing of fat appears considerably less effcient than in the proximal segments of the small intestine.

  20. Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs

    PubMed Central

    Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

    2016-01-01

    With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs. PMID:27455239

  1. Mechanism and rate of glucose absorption differ between an Australian honeyeater (Meliphagidae) and a lorikeet (Loriidae).

    PubMed

    Napier, Kathryn R; McWhorter, Todd J; Fleming, Patricia A

    2008-11-01

    Efficient mechanisms of glucose absorption are necessary for volant animals as a means of reducing mass during flight: they speed up gut transit time and require smaller volume and mass of gut tissue. One mechanism that may be important is absorption via paracellular (non-mediated) pathways. This may be particularly true for nectarivorous species which encounter large quantities of sugar in their natural diet. We investigated the extent of mediated and non-mediated glucose absorption in red wattlebirds Anthochaera carunculata (Meliphagidae) and rainbow lorikeets Trichoglossus haematodus (Loriidae) to test the hypothesis that paracellular uptake accounts for a significant proportion of total glucose uptake in these species. We found that routes of glucose absorption are highly dynamic in both species. In lorikeets, absorption of L-glucose (non-mediated uptake) is slower than that of D-glucose (mediated and non-mediated uptake), with as little as 10% of total glucose absorbed by the paracellular pathway initially (contrasting previous indirect estimates of approximately 80%). Over time, however, more glucose may be absorbed via the paracellular route. Glucose absorption by both mediated and non-mediated mechanisms in wattlebirds occurred at a faster rate than in lorikeets, and wattlebirds also rely substantially on paracellular uptake. In wattlebirds, we recorded higher bioavailability of L-glucose (96+/-3%) compared with D-glucose (57+/-2%), suggesting problems with the in vivo use of radiolabeled d-glucose. Further trials with 3-O-methyl-D-glucose revealed high bioavailability in wattlebirds (90+/-5%). This non-metabolisable glucose analogue remains the probe of choice for measuring uptake rates in vivo, especially in birds in which absorption and metabolism occur extremely rapidly.

  2. Mechanism and rate of glucose absorption differ between an Australian honeyeater (Meliphagidae) and a lorikeet (Loriidae).

    PubMed

    Napier, Kathryn R; McWhorter, Todd J; Fleming, Patricia A

    2008-11-01

    Efficient mechanisms of glucose absorption are necessary for volant animals as a means of reducing mass during flight: they speed up gut transit time and require smaller volume and mass of gut tissue. One mechanism that may be important is absorption via paracellular (non-mediated) pathways. This may be particularly true for nectarivorous species which encounter large quantities of sugar in their natural diet. We investigated the extent of mediated and non-mediated glucose absorption in red wattlebirds Anthochaera carunculata (Meliphagidae) and rainbow lorikeets Trichoglossus haematodus (Loriidae) to test the hypothesis that paracellular uptake accounts for a significant proportion of total glucose uptake in these species. We found that routes of glucose absorption are highly dynamic in both species. In lorikeets, absorption of L-glucose (non-mediated uptake) is slower than that of D-glucose (mediated and non-mediated uptake), with as little as 10% of total glucose absorbed by the paracellular pathway initially (contrasting previous indirect estimates of approximately 80%). Over time, however, more glucose may be absorbed via the paracellular route. Glucose absorption by both mediated and non-mediated mechanisms in wattlebirds occurred at a faster rate than in lorikeets, and wattlebirds also rely substantially on paracellular uptake. In wattlebirds, we recorded higher bioavailability of L-glucose (96+/-3%) compared with D-glucose (57+/-2%), suggesting problems with the in vivo use of radiolabeled d-glucose. Further trials with 3-O-methyl-D-glucose revealed high bioavailability in wattlebirds (90+/-5%). This non-metabolisable glucose analogue remains the probe of choice for measuring uptake rates in vivo, especially in birds in which absorption and metabolism occur extremely rapidly. PMID:18978218

  3. Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance.

    PubMed

    Do, Thi Thu Huong; Hindlet, Patrick; Waligora-Dupriet, Anne-Judith; Kapel, Nathalie; Neveux, Nathalie; Mignon, Virginie; Deloménie, Claudine; Farinotti, Robert; Fève, Bruno; Buyse, Marion

    2014-03-01

    The oligopeptide transporter peptide cotransporter-1 Slc15a1 (PEPT1) plays a major role in the regulation of nitrogen supply, since it is responsible for 70% of the dietary nitrogen absorption. Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters (Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (+40%) and an increased intestinal permeability (+80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue.

  4. Mechanisms of intestinal absorption of the carcinogen MNNG (N-Methyl-N'-nitro-N-nitrosoguanidine)

    SciTech Connect

    Koyama, S.Y.; Hollander, D.; Dadufalza, V.

    1988-06-01

    The authors studied the characteristics and mechanisms of MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) intestinal absorption and the interaction between bile acids and fatty acids and MNNG absorption rat in vivo in male Sprague-Dawley rats. They found that MNNG was absorbed by simple passive diffusion. Transport of MNNG was the highest at pH 6.0. The addition of the bile salt, taurocholate by itself, greatly increased MNNG absorption, while the addition of the long-chain unsaturated fatty acids, oleic and linoleic, decreased the rate of absorption of MNNG. The phospholipid lecithin addition to the perfusate did not change the rate of MNNG absorption. Induction of dietary vitamin A deficiency (serum vitamin A level decreased from 40.9 to 13.7 ..mu..g/dl) did not change the absorption rate of MNNG. These studies demonstrate that bile acids, dietary fatty acids, and the pH of the intestinal content can modify the rate of absorption of this carcinogen by the small intestine. Since initial intestinal absorption determines serum levels and subsequent reabsorption and enterohepatic cycling determines long-term lumenal levels, serum levels, and total body content, factors which modify the rate of intestinal absorption of MNNG could also modify its carcinogenicity.

  5. Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice

    PubMed Central

    Marsollier, Nicolas; Masseboeuf, Myriam; Payros, Gaëlle; Kabani, Catherine; Denom, Jessica; Lacombe, Amélie; Thiers, Jean-Claude; Negre-Salvayre, Anne; Luquet, Serge; Burcelin, Rémy; Cruciani-Guglielmacci, Céline; Magnan, Christophe

    2011-01-01

    Background Daily variations in lipid concentrations in both gut lumen and blood are detected by specific sensors located in the gastrointestinal tract and in specialized central areas. Deregulation of the lipid sensors could be partly involved in the dysfunction of glucose homeostasis. The study aimed at comparing the effect of Medialipid (ML) overload on insulin secretion and sensitivity when administered either through the intestine or the carotid artery in mice. Methodology/Principal Findings An indwelling intragastric or intracarotid catheter was installed in mice and ML or an isocaloric solution was infused over 24 hours. Glucose and insulin tolerance and vagus nerve activity were assessed. Some mice were treated daily for one week with the anti-lipid peroxidation agent aminoguanidine prior to the infusions and tests. The intestinal but not the intracarotid infusion of ML led to glucose and insulin intolerance when compared with controls. The intestinal ML overload induced lipid accumulation and increased lipid peroxidation as assessed by increased malondialdehyde production within both jejunum and duodenum. These effects were associated with the concomitant deregulation of vagus nerve. Administration of aminoguanidine protected against the effects of lipid overload and normalized glucose homeostasis and vagus nerve activity. Conclusions/Significance Lipid overload within the intestine led to deregulation of gastrointestinal lipid sensing that in turn impaired glucose homeostasis through changes in autonomic nervous system activity. PMID:21698161

  6. [Improvement of intestinal absorption of poorly absorbable drugs by various sugar esters].

    PubMed

    Yamamoto, Akira; Katsumi, Hidemasa; Kusamori, Kosuke; Sakane, Toshiyasu

    2014-01-01

    Effects of sucrose fatty acid esters (sugar esters) on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) with various molecular weights were used as model drugs of poorly absorbable drugs. The absorption of CF from the rat small intestine was significantly enhanced in the presence of various sugar esters and a maximal absorption enhancing effect was observed in the presence of 0.5%(w/v) S-1670. The absorption enhancing effect of S-1670 in the small intestine decreased as the molecular weights of drugs increased. Moreover, we evaluated the intestinal membrane damage with or without various sugar esters. These sugar esters (0.5%(w/v)) did not increase the activities of lactate dehydrogenase (LDH), suggesting that these sugar esters did not cause serious membrane damage to the intestinal epithelium. Furthermore, these sugar esters increased membrane fluidity of lipid layers of the intestinal brush border membranes and decreased the transepithelial electrical resistance (TEER) of Caco-2 cells. Therefore, these findings suggested that these sugar esters might improve the intestinal absorption of poorly absorbable drugs via a transcellular and a paracellular pathways.

  7. Regional differences in oxalate absorption by rat intestine: evidence for excessive absorption by the colon in steatorrhoea.

    PubMed Central

    Saunders, D R; Sillery, J; McDonald, G B

    1975-01-01

    Clinical studies suggest that steatorrhoea can be associated with excessive absorption of dietary oxalate. We examined the influence of bile salts, Ca++, and long-chain fatty acid on the absorption of oxalate and water by rat intestine in vivo. Absorption was measured under steady-state conditions during single-pass infusions. Each intestinal segment served as its own control. In jejunum, 10 mM taurocholate, the principal salt in rat bile, depressed absorption of oxalate and water. Absorption was not depressed further by Ca++ or linoleic acid. In ileum, 10 mM taurocholate did not inhibit absorption. Linoleic acid, 2 mM, depressed absorption of both oxalate and water. In colon 10 mM taurocholate decreased absorption. Net water transport was depressed further when linoleic acid was added to the infusion, but oxalate absorption was enhanced. Ca++ negated these effects of linoleic acid. It is concluded that long-chain fatty acids may enhance the absorption of oxalate from the rat colon. This observation may be relevant to understanding hyperoxaluria in patients with steatorrhoea. PMID:1158192

  8. Kinetics of amino acid and glucose absorption following pancreatic diversion in the pig

    NASA Technical Reports Server (NTRS)

    Rerat, A.; Calmes, R.; Corring, T.; Vaissade, P.

    1996-01-01

    An experiment was conducted in the pig to determine the consequences of deprivation of exocrine pancreatic secretion on the composition and quantity of nutrients absorbed after intake of a balanced diet. Five growing pigs (53.8 kg body weight) were fitted with permanent catheters in the portal vein and the carotid artery and with an electromagnetic flow probe around the portal vein to measure the exchanges between the blood and the intestinal lumen. They were also fitted with a permanent catheter in the duct of Wirsung to educe the exocrine pancreatic secretion and another one in the duodenum in order to reintroduce it. In each animal, glucose, amino-N and amino acid absorption as well as insulin and glucagon production were measured over a period of 10 h after the meal (semi-purified diet based on purified starch and containing 180 g fish meal/kg, DM content of the meal 731 g), either in the presence of pancreatic juice (group C: immediate reintroduction), or in the absence of pancreatic juice (group D: deprivation). The deprivation of pancreatic juice provoked a marked depression in the absorption of glucose (D 67.9 (SEM 27.9) g/10 h, C 437.7 (SEM 39.5) g/10 h, P < 0.001), and of amino-N (D 7.55 (SEM 0.54) g/10 h, C 15.80 (SEM 0.79) g/10 h, P < 0.001). The composition of the mixture of amino acids in the portal blood was only slightly modified: only the levels of histidine (P < 0.05) and of valine (P < 0.06, NS) decreased in the absence of pancreatic juice. Insulin production was much lower (by 64%, P < 0.05) in the absence of pancreatic juice whereas that of glucagon was not affected.

  9. Effect of poly-L-arginine on intestinal absorption of hydrophilic macromolecules in rats.

    PubMed

    Yamaki, Tsutomu; Uchida, Masaki; Kuwahara, Yusuke; Shimazaki, Yohei; Ohtake, Kazuo; Kimura, Mitsutoshi; Uchida, Hiroyuki; Kobayashi, Jun; Ogihara, Masahiko; Morimoto, Yasunori; Natsume, Hideshi

    2013-01-01

    We have already reported that poly-L-arginine (PLA) remarkably enhanced the in vivo nasal absorption of hydrophilic macromolecules without producing any significant epithelial damage in rats. In the present study, we examined whether PLA could enhance the absorption of a model hydrophilic macromolecule, fluorescein isothiocyanate-dextran (FD-4), across the intestinal mucosa, as well as the nasal mucosa, by an in situ closed-loop method using the rat intestine. PLA was found to enhance the intestinal absorption of FD-4 in a concentration-dependent manner within the concentrations investigated in this study, but segment-specific differences were found to be associated with this effect (ileum>jejunum>duodenum≧colon). The factors responsible for the segment-specific differences were also investigated by intestinal absorption studies using aprotinin, a trypsin inhibitor, and an analysis of the expression of occludin, a tight junction protein. In the small intestine, the differences in the effect of PLA on the absorption of FD-4 may be related to the enzymatic degradation of PLA. In the colon, the reduced effect of PLA on the absorption of FD-4 may be related to the smaller surface area for absorption and the higher expression of occludin compared with other segments.

  10. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  11. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

    PubMed Central

    Yen, Chi-Liang Eric; Nelson, David W.; Yen, Mei-I

    2015-01-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

  12. Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

    PubMed

    Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

    2015-03-01

    The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation.

  13. Comparison of the effect of sorbitol and glucose on calcium absorption in postmenopausal women

    SciTech Connect

    Francis, R.M.; Peacock, M.; Barkworth, S.A.; Marshall, D.H.

    1986-01-01

    It has been suggested that the oral administration of sorbitol promotes calcium absorption, while glucose has no effect. We have therefore compared the effect of oral sorbitol and glucose on the absorption of radiocalcium from low and high carrier loads in healthy postmenopausal women. In a control group of 20 women given neither sorbitol nor glucose, the mean +/- SEM fractional radiocalcium absorption rate from a low carrier load was 0.65 +/- 0.05 (fraction of dose/h). In a second group of 10 women the fractional absorption rate from the low carrier load was lower (p less than 0.05) with 10 g sorbitol (0.48 +/- 0.05) than with 10 g glucose (0.65 +/- 0.08). Fractional absorption of radiocalcium from a high carrier load measured in a third group of seven women using two isotopes (oral 45Ca, IV 47Ca) was also lower (p less than 0.001) with 10 g sorbitol (0.22 +/- 0.01, fraction/3 h) than with 10 g glucose (0.29 +/- 0.02). The results suggest that calcium absorption from a low carrier load is unaltered by glucose but that absorption of calcium from both low and high carrier loads is lower with sorbitol than with glucose.

  14. Intestinal nutrient absorption - A biomarker for deleterious heavy metals in aquatic environments

    SciTech Connect

    Farmanfarmaian, A. )

    1988-09-01

    The deleterious effects of heavy metals on absorptive processes at the membrane surface will be summarized. Among the deleterious heavy metal chlorides (HgCl{sub 2}, CH{sub 3}HgCl, CdCl{sub 2}, CoCl{sub 2}, SrCl{sub 2}) tested HgCl{sub 2}, CH{sub 3}HgCl, and CdCl{sub 2} inhibit the absorption of several amino acids and sugars (L-leucine, L-methionine, L-isoleucine, L-lysine, cyclolencine, D-glucose, and D-galactose). The dose dependent inhibition of L-leucine uptake by HgCl{sub 2} is shown in a number of fish from different collection sites representing nektonic plankton feeders as well as demersal carnivores. The same type of data is shown for both HgCl{sub 2} and HC{sub 3}HgCl in the case of the commercially important summer flounder. Since the overall rate of intestinal absorption of amino acids and sugars involves the three processes of simple diffusion, protein-mediated facilitated diffusions, and protein-mediated sodium dependent active transport, the inhibition of the overall rate may not be sensitive enough as a biomarker. However, the active component, which alone accumulates essential amino acids in the tissue, appears to be very sensitive and can be used as a biomarker. The terminal tissue-to-medium (T/M) ratio of L-leucine concentration shows a 2-3 fold accumulation in the absence of mercury. Since the diffusional components can at best equilibrate L-leucine across the membrane % inhibition of the active component can be calculated after subtracting 1 from the experimental T/M values. The resulting inhibition is very sever ranging from approximately 50-100% for HgCl{sub 2} and 20-70% for CH{sub 3}HgCl over a range of 5-20 ppm of mercury.

  15. Human in vivo regional intestinal permeability: quantitation using site-specific drug absorption data.

    PubMed

    Sjögren, Erik; Dahlgren, David; Roos, Carl; Lennernäs, Hans

    2015-06-01

    Application of information on regional intestinal permeability has been identified as a key aspect of successful pharmaceutical product development. This study presents the results and evaluation of an approach for the indirect estimation of site-specific in vivo intestinal effective permeability (Peff) in humans. Plasma concentration-time profiles from 15 clinical studies that administered drug solutions to specific intestinal regions were collected and analyzed. The intestinal absorption rate for each drug was acquired by deconvolution, using historical intravenous data as reference, and used with the intestinal surface area and the dose remaining in the lumen to estimate the Peff. Forty-three new Peff values were estimated (15 from the proximal small intestine, 11 from the distal small intestine, and 17 from the large intestine) for 14 active pharmaceutical ingredients representing a wide range of biopharmaceutical properties. A good correlation (r(2) = 0.96, slope = 1.24, intercept = 0.030) was established between these indirect jejunal Peff estimates and jejunal Peff measurements determined directly using the single-pass perfusion double balloon technique. On average, Peff estimates from the distal small intestine and large intestine were 90% and 40%, respectively, of those from the proximal small intestine. These results support the use of the evaluated deconvolution method for indirectly estimating regional intestinal Peff in humans. This study presents the first comprehensive data set of estimated human regional intestinal permeability values for a range of drugs. These biopharmaceutical data can be used to improve the accuracy of gastrointestinal absorption predictions used in drug development decision-making.

  16. The absorption of fat by intestine of golden hamster in vitro.

    PubMed

    STRAUSS, E W

    1963-06-01

    Everted sacs of intestine from golden hamsters were incubated at 37 degrees C for at least 1 hour in vitro with emulsified lipid after removal of both pancreatic lipase and bile salts. The fine structure of intestinal epithelium is well preserved under these conditions. Absorption of fat by the intestinal mucosa in vitro closely resembles lipid absorption in vivo, as observed by both light and electron microscopy. The physiological significance of these observations is discussed. Tubular elements of the agranular endoplasmic reticulum are often strikingly abundant in the apical cytoplasm of intestinal absorptive cells. These have a role in the intracellular transport of fat since they frequently contain droplets of lipid derived from the incubation medium. The rate of fat accumulation in the epithelium appears to be proportional to the concentration in the medium.

  17. Gastric, intestinal and colonic absorption of a series of beta-blockers in the rat.

    PubMed

    Vilà, J I; Calpena, A C; Obach, R; Domenech, J

    1992-08-01

    Gastric, intestinal and colonic absorption rates of a series of eleven beta-blockers (alprenolol hydrochloride, atenolol, bunolol hydrochloride, penbutolol sulphate, pronethalol hydrochloride, metoprolol, oxprenolol, bevantolol, bufuralol, propranolol hydrochloride and timolol maleate) were estimated using Doluisio's method. The gastric absorption rate was very low and the absorption rate constant could not be assessed accurately in all cases. In the small intestine, the absorption rate constants, Ka, at pH 6.2 ranged between 0.38 h-1 for atenolol and 4.28 h-1 for penbutolol. In the colon, the rate of drug absorption at pH 7.5 ranged between 0.12 h-1 for atenolol and 2.15 h-1 for penbutolol. In most cases, colonic absorption rate constants were of the same order as those obtained in the small intestine, demonstrating the good penetrability through colonic membrane of the series studied. The relationship between absorption rate constants found in the small intestine and colon and the partition constant ([1/Rf]-1), was studied for this non-homologous series of beta-blocker drugs. In both cases, the functional hyperbolic absorption model proposed by Wagner and Sedman [1973] was the most representative.

  18. [Absorption of flavonoids from Abelmoschus manihot extract by in situ intestinal perfusion].

    PubMed

    Xue, Cai-fu; Guo, Jian-ming; Qian, Da-wei; Duan, Jin-ao; Shu, Yan

    2011-04-01

    To explore the mechanism of the absorption of flavonoids from Abelmoschus manihot flowers, in situ intestinal recirculation was performed to study the effect of the absorption at different concentrations and different intestinal regions. To evaluate the conditions of the absorption of six flavonoids from Abelmoschus manihot flowers, the concentrations of Abelmoschus manihot in the perfusion solution were determined by HPLC at predesigned time. And we have investigated the inhibitory effect of six flavonoids from Abelmoschus manihot flowers on P-glycoprotein (P-gp) drug efflux pump. The results demonstrated that the absorption rates of flavonoids from Abelmoschus manihot flowers are not significantly different (P > 0.05) at various drug concentrations, the absorption of flavonoids from Abelmoschus manihot flowers is a first-order process with the passive diffusion mechanism. The absorption rates of each of flavonoids are significantly different. The absorption rate of flavonoid glycoside was lower than that of aglycone; the flavonoids from Abelmoschus manihot flowers could be absorbed in all of the intestinal segments. The best parts of intestine to absorb hyperoside and myricetin are jejunum and duodenum, separately. Verapamil could enhance the absorption of isoquercitrin, hyperoside, myricetin and quercetin-3'-O-glucoside by inhibiting P-glycoprotein (P-gp) drug efflux pump.

  19. Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice.

    PubMed

    Aspenström-Fagerlund, Bitte; Tallkvist, Jonas; Ilbäck, Nils-Gunnar; Glynn, Anders W

    2015-09-01

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  20. The 13C/2H-glucose test for determination of small intestinal lactase activity.

    PubMed

    Vonk, R J; Stellaard, F; Priebe, M G; Koetse, H A; Hagedoorn, R E; De Bruijn, S; Elzinga, H; Lenoir-Wijnkoop, I; Antoine, J M

    2001-03-01

    To diagnose hypolactasia, determination of lactase enzyme activity in small intestinal biopsy material is considered to be the golden standard. Because of its strongly invasive character and the sampling problems, alternative methods have been looked for. We analysed the 13C-glucose response in serum after consumption of 25 g of naturally enriched 13C-lactose. As an internal standard, 0.5 g of 2H-glucose was added and the 2H-glucose response in serum was measured simultaneously. The studies were performed in healthy volunteers with a background of genetically determined lactase nonpersistence (n = 12; low lactase activity) and lactase persistence (n = 27; high lactase activity). The results were compared with those of the lactose hydrogen breath test, the lactose 13CO2 breath test and the previously described 13C-lactose digestion test. After consumption of 13C-lactose and 2H-glucose, the mean ratio 13C-glucose/2H-glucose concentration in serum at 45-75 min was 0.26 +/- 0.09 in the low lactase activity group and 0.93 +/- 0.17 in the high lactase activity group (P < 0.01). Threshold of the ratio between digesters and maldigesters was calculated as 0.46. Accuracy of the new test was superior to all other tests. We conclude that the 13C/2H-glucose test has the potential of determining the small intestinal lactase activity in vivo and of estimating the amount of lactose which is digested in the small intestine. PMID:11264650

  1. The 13C/2H-glucose test for determination of small intestinal lactase activity.

    PubMed

    Vonk, R J; Stellaard, F; Priebe, M G; Koetse, H A; Hagedoorn, R E; De Bruijn, S; Elzinga, H; Lenoir-Wijnkoop, I; Antoine, J M

    2001-03-01

    To diagnose hypolactasia, determination of lactase enzyme activity in small intestinal biopsy material is considered to be the golden standard. Because of its strongly invasive character and the sampling problems, alternative methods have been looked for. We analysed the 13C-glucose response in serum after consumption of 25 g of naturally enriched 13C-lactose. As an internal standard, 0.5 g of 2H-glucose was added and the 2H-glucose response in serum was measured simultaneously. The studies were performed in healthy volunteers with a background of genetically determined lactase nonpersistence (n = 12; low lactase activity) and lactase persistence (n = 27; high lactase activity). The results were compared with those of the lactose hydrogen breath test, the lactose 13CO2 breath test and the previously described 13C-lactose digestion test. After consumption of 13C-lactose and 2H-glucose, the mean ratio 13C-glucose/2H-glucose concentration in serum at 45-75 min was 0.26 +/- 0.09 in the low lactase activity group and 0.93 +/- 0.17 in the high lactase activity group (P < 0.01). Threshold of the ratio between digesters and maldigesters was calculated as 0.46. Accuracy of the new test was superior to all other tests. We conclude that the 13C/2H-glucose test has the potential of determining the small intestinal lactase activity in vivo and of estimating the amount of lactose which is digested in the small intestine.

  2. Ethanol inhibition of glucose absorption in isolated, perfused small bowel of rats

    SciTech Connect

    Cobb, C.F.; Van Thiel, D.H.; Wargo, J.

    1983-08-01

    There is evidence for both humans and rats that malnutrition frequently occurs when ethanol is chronically ingested. Small bowel /sup 14/C-labelled glucose absorption was measured with an ex vivo system in which the small bowel of the rat was surgically removed and then arterially perfused with an artificial medium. Glucose absorption for a control group of seven rats was 248 +/- 8 microM/min/gm dry weight of small bowel (mean +/- SEM). This was significantly greater than the value 112 +/- 12 microM/min/gm dry weight (P less than 0.005) for a group of five rats in which a competitive inhibitor of glucose absorption, phlorizin (0.2 mM), was added to the bowel lumen. In the presence of 3% ethanol within the gut lumen of five rats, glucose absorption was also reduced (to 131 +/- 12 microM/min/gm dry weight) compared to absorption in the control group (P less than 0.005). The calculated amount of glucose absorbed was corrected for metabolism to lactate and carbon dioxide. We conclude that both phlorizin and ethanol inhibit glucose absorption in the isolated and perfused small bowel of rats and that probably at least part of the malnutrition in ethanol-fed rats is due to glucose malabsorption.

  3. Effects of pentagastrin on intestinal absorption and blood flow in the anaesthetized dog.

    PubMed

    Mailman, D

    1980-10-01

    1. Pentagastrin (1, 10 micrograms/min) was infused I.V. into fed and fasted anaesthetized dogs and the intestinal absorption of NaCl and H2O and blood flow were determined. The influence of pentagastrin-induced cardiovascular changes on absorption was investigated. 2. 22Na and 3H2O were used to determine the unidirectional Na and H2O fluxes from saline perfused through the ileal lumen and the clearances of 3H2O were used to calculate total and absorptive site blood flow. 3. Ileal absorption of Na and H2O was reduced by 10 micrograms/min pentagastrin due primarily to significant increases in the secretory flux of Na and decreases in the absorptive flux of H2O in both fed and fasted animals. 4. Neither total intestinal blood flow, arterial nor mesenteric vein pressure were changed by pentagastrin but absorptive site blood flow was decreased in fasted but not in fed dogs. 5. Pretreatment with atropine reduced the effects of pentagastrin but pretreatment with guanethidine potentiated the effects of pentagastrin. 6. Absorptive site blood flow was positively linearly correlated with the absorptive fluxes of both Na and H2O. The relationships between the secretory fluxes of Na and H2O and estimated capillary pressure were changed from a positive relationship in control periods to a less positive or negative relationship following pentagastrin. 7. It was concluded that pentagastrin reduces intestinal absorption through both a cardiovascular effect and an effect on the intestinal epithelium. Also, there is a strong autonomic component in the effects of pentagastrin on intestinal absorption.

  4. Immunological control of drug absorption from the gastrointestinal tract: the mechanism whereby intestinal anaphylaxis interferes with the intestinal absorption of bromthymol blue in the rat.

    PubMed

    Yamamoto, A; Utsumi, E; Sakane, T; Hamaura, T; Nakamura, J; Hashida, M; Sezaki, H

    1986-05-01

    Rats were immunized intraperitoneally with ovalbumin and the disappearance of bromthymol blue (BTB) from the intestinal lumen, its accumulation in the tissue, and its net absorption were examined by means of an in-situ recirculation technique during local anaphylaxis. The disappearance of BTB from the intestinal lumen and its net absorption were significantly reduced, but there was no significant effect on its accumulation in the tissue. The pH value of the luminal solution and the perfusate volume were not influenced by intraluminal challenge with the antigen in ovalbumin-immunized rats. In addition, no significant effect was observed on intestinal permeability to BTB in the in-vitro everted sac technique. The intestinal blood flow, measured by a hydrogen clearance method, was not reduced significantly by the intraluminal exposure to antigen. There was enhanced Evans Blue leakage and mucus release in the perfusate after intraluminal challenge with ovalbumin in ovalbumin-immunized rats, but not in non-immunized rats. A significant increase of BTB binding with macromolecular substances in the perfusate was observed during the local anaphylaxis. These findings suggest that the decreased absorption of BTB is due to the interaction with the macromolecular substances in the perfusate during local anaphylaxis. PMID:2872311

  5. Concord and Niagara Grape Juice and Their Phenolics Modify Intestinal Glucose Transport in a Coupled in Vitro Digestion/Caco-2 Human Intestinal Model

    PubMed Central

    Moser, Sydney; Lim, Jongbin; Chegeni, Mohammad; Wightman, JoLynne D.; Hamaker, Bruce R.; Ferruzzi, Mario G.

    2016-01-01

    While the potential of dietary phenolics to mitigate glycemic response has been proposed, the translation of these effects to phenolic rich foods such as 100% grape juice (GJ) remains unclear. Initial in vitro screening of GJ phenolic extracts from American grape varieties (V. labrusca; Niagara and Concord) suggested limited inhibitory capacity for amylase and α-glucosidase (6.2%–11.5% inhibition; p < 0.05). Separately, all GJ extracts (10–100 µM total phenolics) did reduce intestinal trans-epithelial transport of deuterated glucose (d7-glu) and fructose (d7-fru) by Caco-2 monolayers in a dose-dependent fashion, with 60 min d7-glu/d7-fru transport reduced 10%–38% by GJ extracts compared to control. To expand on these findings by assessing the ability of 100% GJ to modify starch digestion and glucose transport from a model starch-rich meal, 100% Niagara and Concord GJ samples were combined with a starch rich model meal (1:1 and 1:2 wt:wt) and glucose release and transport were assessed in a coupled in vitro digestion/Caco-2 cell model. Digestive release of glucose from the starch model meal was decreased when digested in the presence of GJs (5.9%–15% relative to sugar matched control). Furthermore, transport of d7-glu was reduced 10%–38% by digesta containing bioaccessible phenolics from Concord and Niagara GJ compared to control. These data suggest that phenolics present in 100% GJ may alter absorption of monosaccharides naturally present in 100% GJ and may potentially alter glycemic response if consumed with a starch rich meal. PMID:27399765

  6. Green tea polyphenols inhibit the sodium-dependent glucose transporter of intestinal epithelial cells by a competitive mechanism.

    PubMed

    Kobayashi, Y; Suzuki, M; Satsu, H; Arai, S; Hara, Y; Suzuki, K; Miyamoto, Y; Shimizu, M

    2000-11-01

    Intestinal glucose uptake is mainly performed by the sodium-dependent glucose transporter, SGLT1. The transport activity of SGLT1 was markedly inhibited by green tea polyphenols, this inhibitory activity being most pronounced in polyphenols having galloyl residues such as epicatechin gallate (ECg) and epigallocatechin gallate (EGCg). Experiments using brush-border membrane vesicles obtained from the rabbit small intestine demonstrated that ECg inhibited SGLT1 in a competitive manner, although ECg itself was not transported via SGLT1. The present results suggest that tea polyphenols such as ECg interact with SGLT1 as antagonist-like molecules, possibly playing a role in controlling the dietary glucose uptake in the intestinal tract.

  7. Involvement of intestinal permeability in the oral absorption of clarithromycin and telithromycin.

    PubMed

    Togami, Kohei; Hayashi, Yoshiaki; Chono, Sumio; Morimoto, Kazuhiro

    2014-09-01

    The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration-time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3- and 1.6-fold, respectively, after concomitant oral administration of verapamil as a P-glycoprotein (P-gp) inhibitor. Further, an in vitro transport experiment was performed using Caco-2 cell monolayers as a model of intestinal epithelial cells. The apical-to-basolateral transport of CAM and TEL through the Caco-2 cell monolayers was lower than their basolateral-to-apical transport. Verapamil and bromosulfophthalein as a multidrug resistance-associated proteins (MRPs) inhibitor significantly increased the apical-to-basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P-gp and MRPs on the intestinal epithelial cells.

  8. Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.

    PubMed

    Mudaliar, Sunder; Polidori, David; Zambrowicz, Brian; Henry, Robert R

    2015-12-01

    Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors. PMID:26604280

  9. Measurement of the absorption coefficient of a glucose solution through transmission of light and polarymetry techniques

    NASA Astrophysics Data System (ADS)

    Yáñez M., J.

    2011-10-01

    Diabetes is a disease with no cure, but can be controlled to improve the quality of life of sufferers. Currently there are means to control, but this means they have the disadvantage that in order to measure the amount of glucose is necessary to take blood samples that are painful. This paper presents a system for measuring glucose using non-invasive optical techniques: using absorption spectroscopy and polarimetry technique. It shows the results obtained from experiments done on samples containing distilled water and different amounts of glucose to study the absorption coefficient of glucose with both techniques. Water is used because it is one of the main elements in the blood and interferes with glucose measurement. This experiment will develop a prototype to measure glucose through a non-invasive technique.

  10. Glucose absorption, hormonal release and hepatic metabolism after guar gum ingestion

    NASA Technical Reports Server (NTRS)

    Simoes Nunes, C.; Malmlof, K.

    1992-01-01

    Six non-anaesthetized Large White pigs (mean body weight 59 +/- 1.7 kg) were fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein and with electromagnetic flow probes around the portal vein and the hepatic artery. The animals were provided a basal none-fibre diet (diet A) alone or together with 6% guar gum (diet B) or 15% purified cellulose (diet C). The diets were given for 1 week and according to a replicated 3 x 3 latin-square design. On the last day of each adaptation period test meals of 800 g were given prior to blood sampling. The sampling was continued for 8 h. Guar gum strongly reduced the glucose absorption as well as the insulin, gastric inhibitory polypeptide (GIP) and insulin-like growth factor-1 (IGF-1) production. However, the reduction in peripheral blood insulin levels caused by guar gum was not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly produced by the gut. The liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut produced IGF-1. Guar gum ingestion also appeared to decrease pancreatic glucagon secretion. Cellulose at the level consumed had very little effect on the parameters considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the latter internal metabolic effects.

  11. Intestinal perfusion studies in tropical sprue. 1. Amino acid and dipeptide absorption.

    PubMed Central

    Hellier, M D; Radhakrishnan, A N; Ganapathy, V; Mathan, V I; Baker, S J

    1976-01-01

    Intestinal absorption of glycine 20 mmol/1, glycyl-glycine 10 mmol/1 plus L-leucine 10 mmol/1, and glycyl-L-leucine 10 mmol/1 has been studied by intestinal perfusion in 11 patients with tropical sprue and 10 control subjects. The patients with sprue had a significant reduction in the rate of absorption of glycine from a 20 mmol/1 solution, but there were no significant differences in the absorption of the other substances. The failure to demonstrate any difference in the absorption of these substances is probably related to their low concentration relative to the maximum absorptive capacity of the intestine. In both groups of subjects the kinetic advantage of glycyl-glycine absorption as compared with glycine absorption was maintained. When the dipeptides were perfused, free amino acids appeared in the perfusate presumably by "back diffusion" from the mucosal cells. In the case of glycyl-L-leucine considerably more glycine and leucine were found in the perfusate in patients with sprue than in the control subjects. There was no correlation between peptide absorption and the concentration of total glycly-glycine hydrolase and glycyl-L-leucine hydrolase, measured as combined brush border and cytosol enzymes. The concentrations of these enzymes were similar in both groups of subjects. PMID:964683

  12. Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat.

    PubMed

    McGinn, B J; Morrison, J D

    2016-06-28

    Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B(29)-Lys-cholyl-insulin and B(1)-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B(29)-Lys-cholyl-insulin when infused into the ileum, B(1)-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B(1)-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B(1)-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation.

  13. Sleeve gastrectomy does not cause hypertrophy and reprogramming of intestinal glucose metabolism in rats

    PubMed Central

    Mumphrey, Michael B.; Hao, Zheng; Townsend, R. Leigh; Patterson, Laurel M.; Berthoud, Hans-Rudolf

    2015-01-01

    BACKGROUND & AIMS Clinical studies have shown similar rapid improvements in body mass and glycemic control after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG). Evidence suggests that adaptive intestinal tissue growth and reprogramming of intestinal glucose disposal plays a key role in the beneficial effects on glucose homeostasis after RYGB, but it is not known whether such adaptive changes also occur after sleeve gastrectomy. METHODS High-fat diet-induced obese rats were subjected to either VSG or RYGB and intestinal growth and functional adaptations were assessed by using morphometric, immunohistochemical and immuno-blot techniques, 3 months after surgery or sham surgery. RESULTS The cross-sectional areas of the Roux and common limbs are significantly increased after RYGB compared with sham surgery (Roux limb: 17.1 ± 4.0 vs. 5.5 ± 0.1 mm2; common limb: 11.7 ± 0.6 vs. 5.1 ± 0.5 mm2; p < 0.01), but the cross-sectional area of the corresponding jejunum is not different from controls after VSG. Similarly, mucosal thickness and the number of GLP-1 cells are not increased after VSG. Protein expression of hexokinase II is increased four-fold (p <0.01) in the Roux limb after RYGB, but not in the jejunum after VSG. CONCLUSIONS Adaptive hypertrophy and reprogramming of glucose metabolism in the small intestine are not necessary for VSG to improve body composition and glycemic control. The similar beneficial effects of VSG and RYGB on glucose homeostasis might be mediated by different mechanisms. PMID:25566744

  14. In vitro absorption of gamma-globulin by neonatal intestinal epithelium of the pig.

    PubMed

    Lecce, J G

    1966-06-01

    1. An in vitro method, using fluorescent gamma-globulin and everted neonatal pig's intestinal slices, for the study of the active transport of large molecules is described.2. Uptake of gamma-globulin occurred within 15 min and required no exogenous substrates.3. In vitro absorption of gamma-globulin by intestinal epithelium was limited to the neonatal pig and 5-day-old mouse. No uptake was seen in intestines from a mature mouse, a pig with diarrhoea, a normal pig, a mature rabbit, a guinea-pig, a chick, and a chick embryo. Chick embryo yolk sac readily took up gamma-globulin.4. Rings of everted intestinal epithelium remained active (still absorbed gamma-globulin) after incubating for 4-6 hr in balanced salt solution (BSS).5. Uptake of gamma-globulin required oxygen and sodium and was reversibly inhibited by metabolic antagonists such as iodoacetate, arsenate, fluoride, 4,6-dinitro-varphi-cresol, phlorrhizin, anaerobiosis and cold. Under the conditions of the test, large colloidal molecules did not inhibit uptake of gamma-globulin.6. Similar results (although not as clear-cut) with metabolic inhibitors were obtained with preparations of chick embryo yolk sacs.7. Injuring mature pig's intestinal epithelium with surface-active agents did not produce non-specific absorption artifacts that resembled the specific absorption found in immature pig's intestinal epithelium.

  15. Intestinal paracellular absorption is necessary to support the sugar oxidation cascade in nectarivorous bats.

    PubMed

    Rodriguez-Peña, Nelly; Price, Edwin R; Caviedes-Vidal, Enrique; Flores-Ortiz, Cesar M; Karasov, William H

    2016-03-01

    We made the first measurements of the capacity for paracellular nutrient absorption in intact nectarivorous bats. Leptonycteris yerbabuenae (20 g mass) were injected with or fed inert carbohydrate probes L-rhamnose and D(+)-cellobiose, which are absorbed exclusively by the paracellular route, and 3-O-methyl-D-glucose (3OMD-glucose), which is absorbed both paracellularly and transcellularly. Using a standard pharmacokinetic technique, we collected blood samples for 2 h after probe administration. As predicted, fractional absorption (f) of paracellular probes declined with increasing Mr in the order of rhamnose (f=0.71)>cellobiose (f=0.23). Absorption of 3OMD-glucose was complete (f=0.85; not different from unity). Integrating our data with those for glucose absorption and oxidation in another nectarivorous bat, we conclude that passive paracellular absorption of glucose is extensive in nectarivorous bat species, as in other bats and small birds, and necessary to support high glucose fluxes hypothesized for the sugar oxidation cascade. PMID:26985050

  16. Intestinal paracellular absorption is necessary to support the sugar oxidation cascade in nectarivorous bats.

    PubMed

    Rodriguez-Peña, Nelly; Price, Edwin R; Caviedes-Vidal, Enrique; Flores-Ortiz, Cesar M; Karasov, William H

    2016-03-01

    We made the first measurements of the capacity for paracellular nutrient absorption in intact nectarivorous bats. Leptonycteris yerbabuenae (20 g mass) were injected with or fed inert carbohydrate probes L-rhamnose and D(+)-cellobiose, which are absorbed exclusively by the paracellular route, and 3-O-methyl-D-glucose (3OMD-glucose), which is absorbed both paracellularly and transcellularly. Using a standard pharmacokinetic technique, we collected blood samples for 2 h after probe administration. As predicted, fractional absorption (f) of paracellular probes declined with increasing Mr in the order of rhamnose (f=0.71)>cellobiose (f=0.23). Absorption of 3OMD-glucose was complete (f=0.85; not different from unity). Integrating our data with those for glucose absorption and oxidation in another nectarivorous bat, we conclude that passive paracellular absorption of glucose is extensive in nectarivorous bat species, as in other bats and small birds, and necessary to support high glucose fluxes hypothesized for the sugar oxidation cascade.

  17. Glucose Transport into Everted Sacks of Intestine of Mice: A Model for the Study of Active Transport.

    ERIC Educational Resources Information Center

    Deyrup-Olsen, Ingrith; Linder, Alison R.

    1979-01-01

    Described is a laboratory procedure which uses the small intestines of mice as models for the transport of glucose and other solutes. Demonstrations are suitable for either introductory or advanced physiology courses. (RE)

  18. Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation.

    PubMed

    Yeap, Yan Yan; Trevaskis, Natalie L; Quach, Tim; Tso, Patrick; Charman, William N; Porter, Christopher J H

    2013-05-01

    The oral bioavailability of poorly water-soluble drugs (PWSD) is often significantly enhanced by coadministration with lipids in food or lipid-based oral formulations. Coadministration with lipids promotes drug solubilization in intestinal mixed micelles and vesicles, however, the mechanism(s) by which PWSD are absorbed from these dispersed phases remain poorly understood. Classically, drug absorption is believed to be a product of the drug concentration in free solution and the apparent permeability across the absorptive membrane. Solubilization in colloidal phases such as mixed micelles increases dissolution rate and total solubilized drug concentrations, but does not directly enhance (and may reduce) the free drug concentration. In the absence of changes to cellular permeability (which is often high for lipophilic, PWSD), significant changes to membrane flux are therefore unexpected. Realizing that increases in effective dissolution rate may be a significant driver of increases in drug absorption for PWSD, we explore here two alternate mechanisms by which membrane flux might also be enhanced: (1) collisional drug absorption where drug is directly transferred from lipid colloidal phases to the absorptive membrane, and (2) supersaturation-enhanced drug absorption where bile mediated dilution of lipid colloidal phases leads to a transient increase in supersaturation, thermodynamic activity and absorption. In the current study, collisional uptake mechanisms did not play a significant role in the absorption of a model PWSD, cinnarizine, from lipid colloidal phases. In contrast, bile-mediated dilution of model intestinal mixed micelles and vesicles led to drug supersaturation. For colloids that were principally micellar, supersaturation was maintained for a period sufficient to promote absorption. In contrast, for primarily vesicular systems, supersaturation resulted in rapid drug precipitation and no increase in drug absorption. This work suggests that ongoing

  19. Intestinal absorption of 5 chromium compounds in young black ducks (Anas rubripes)

    USGS Publications Warehouse

    Eastin, W.C.; Haseltine, S.D.; Murray, H.C.

    1980-01-01

    An in vivo intestinal perfusion technique was used to measure the absorption rates of five Cr compounds in black ducks. Cr was absorbed from saline solutions of KCr(SO4 )2 and CrO3 at a rate about 1.5 to 2.0 times greater than from solutions of Cr, Cr(NO3 )3, and Cr(C5H7O2)3. These results suggest the ionic form of Cr in solution may be an important factor in determining absorption of Cr compounds from the small intestine.

  20. Dietary Lipid and Carbohydrate Interactions: Implications on Lipid and Glucose Absorption, Transport in Gilthead Sea Bream (Sparus aurata) Juveniles.

    PubMed

    Castro, Carolina; Corraze, Geneviève; Basto, Ana; Larroquet, Laurence; Panserat, Stéphane; Oliva-Teles, Aires

    2016-06-01

    A digestibility trial was performed with gilthead sea bream juveniles (IBW = 72 g) fed four diets differing in lipid source (fish oil, FO; or a blend of vegetable oil, VO) and starch content (0 %, CH-; or 20 %, CH+) to evaluate the potential interactive effects between carbohydrates and VO on the processes involved in digestion, absorption and transport of lipids and glucose. In fish fed VO diets a decrease in lipid digestibility and in cholesterol (C), High Density Lipoprotein(HDL)-C and Low Density Lipoprotein (LDL)-C (only in CH+ group) were recorded. Contrarily, dietary starch induced postprandial hyperglycemia and time related alterations on serum triacylglycerol (TAG), phospholipid (PL) and C concentrations. Fish fed a CH+ diet presented lower serum TAG than CH- group at 6 h post-feeding, and the reverse was observed at 12 h post-feeding for TAG and PL. Lower serum C and PL at 6 h post-feeding were recorded only in VOCH+ group. No differences between groups were observed in hepatic and intestinal transcript levels of proteins involved in lipid transport and hydrolysis (FABP, DGAT, GPAT, MTP, LPL, LCAT). Lower transcript levels of proteins related to lipid transport (ApoB, ApoA1, FABP2) were observed in the intestine of fish fed the CH+ diet, but remained unchanged in the liver. Overall, transcriptional mechanisms involved in lipid transport and absorption were not linked to changes in lipid serum and digestibility. Dietary starch affected lipid absorption and transport, probably due to a delay in lipid absorption. This study suggests that a combination of dietary VO and starch may negatively affect cholesterol absorption and transport.

  1. Dietary Lipid and Carbohydrate Interactions: Implications on Lipid and Glucose Absorption, Transport in Gilthead Sea Bream (Sparus aurata) Juveniles.

    PubMed

    Castro, Carolina; Corraze, Geneviève; Basto, Ana; Larroquet, Laurence; Panserat, Stéphane; Oliva-Teles, Aires

    2016-06-01

    A digestibility trial was performed with gilthead sea bream juveniles (IBW = 72 g) fed four diets differing in lipid source (fish oil, FO; or a blend of vegetable oil, VO) and starch content (0 %, CH-; or 20 %, CH+) to evaluate the potential interactive effects between carbohydrates and VO on the processes involved in digestion, absorption and transport of lipids and glucose. In fish fed VO diets a decrease in lipid digestibility and in cholesterol (C), High Density Lipoprotein(HDL)-C and Low Density Lipoprotein (LDL)-C (only in CH+ group) were recorded. Contrarily, dietary starch induced postprandial hyperglycemia and time related alterations on serum triacylglycerol (TAG), phospholipid (PL) and C concentrations. Fish fed a CH+ diet presented lower serum TAG than CH- group at 6 h post-feeding, and the reverse was observed at 12 h post-feeding for TAG and PL. Lower serum C and PL at 6 h post-feeding were recorded only in VOCH+ group. No differences between groups were observed in hepatic and intestinal transcript levels of proteins involved in lipid transport and hydrolysis (FABP, DGAT, GPAT, MTP, LPL, LCAT). Lower transcript levels of proteins related to lipid transport (ApoB, ApoA1, FABP2) were observed in the intestine of fish fed the CH+ diet, but remained unchanged in the liver. Overall, transcriptional mechanisms involved in lipid transport and absorption were not linked to changes in lipid serum and digestibility. Dietary starch affected lipid absorption and transport, probably due to a delay in lipid absorption. This study suggests that a combination of dietary VO and starch may negatively affect cholesterol absorption and transport. PMID:27023202

  2. Intestinal folate binding protein (FBP) and folate absorption in the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1986-03-01

    The folate in milk is bound to high affinity FBPs but it is unknown whether this binding affects intestinal transport of milk folate in the suckling rat. The authors examined the FBP activity of segments of the GI tract in fed and fasting states. Under fed conditions, the FBP activity in the mucosa of the stomach and proximal small intestine were similar (0.28 and 0.32 pMole folic acid binding/mg protein, N.S.). Both demonstrated less activity than the mucosa of the distal small intestine (1.31 pMole/mg protein, P < .001). A 6 hr fast produced no change in the FBP activity in the stomach or proximal small intestine but resulted in a 42% decrease in the distal small intestine (p < .01). Intestinal transport of unbound and FB-bound H/sup 3/pteryolmonoglutamate (H/sup 3/PGA) was examined in suckling rats by the intestinal loop model. Unbound H/sup 3/PGA demonstrated greater lumenal disappearance in the proximal segment of the small intestine compared to the distal segment (79% vs. 56%, P < .001) whereas the bound H/sup 3/PGA demonstrated greater lumenal disappearance in the distal segment (36% vs. 21%, p < .005). That porton of FBP activity in the distal small intestine that disappears with fasting may represent FBP absorbed from the lumen of the intestine. The FBP-bound folate in milk appears to be absorbed in the suckling rat by a mechanism that favors the distal small intestine and is different from the mechanism responsible for absorption of the unbound folate.

  3. In situ absorption in rat intestinal tract of solid dispersion of annonaceous acetogenins.

    PubMed

    Dang, Yun-Jie; Feng, Han-Zhou; Zhang, Limei; Hu, Chun-Hui; Zhu, Chun-Yan

    2012-01-01

    Isolated from Annona squamosa L, Annonaceous acetogenins (ACGs) exhibit a broad range of biological properties yet absorbed badly due to the low solubility. Solid dispersion in polyethylene glycol 4000 (PEG 4000) has been developed to increase the solubility and oral absorption of ACGs. The formulation of ACGS-solid dispersion was optimized by a simplex lattice experiment design and carried out by a solvent-fusion method. We studied the absorption property of ACGs in rat's intestine, which showed there was a good absorption and uptake percentages with solid dispersion. The study on uptake percentage in different regions of rat's intestine attested that the duodenum had the best permeability, followed by jejunum, ileum, and colon in order with no significant differences. So the paper drew the conclusion that solid dispersion could improve the solubility and oral absorption of annonaceous acetogenins. PMID:22536222

  4. Mechanisms of guanylin action on water and ion absorption at different regions of seawater eel intestine.

    PubMed

    Ando, Masaaki; Wong, Marty K S; Takei, Yoshio

    2014-09-15

    Guanylin (GN) inhibited water absorption and short-circuit current (Isc) in seawater eel intestine. Similar inhibition was observed after bumetanide, and the effect of bumetanide was abolished by GN or vice versa, suggesting that both act on the same target, Na(+)-K(+)-2Cl(-) cotransporter (NKCC), which is a key player for the Na(+)-K(+)-Cl(-) transport system responsible for water absorption in marine teleost intestine. However, effect of GN was always greater than that of bumetanide: 10% greater in middle intestine (MI) and 40% in posterior intestine (PI) for Isc, and 25% greater in MI and 34% in PI for water absorption. After treatment with GN, Isc decreased to zero, but 20-30% water absorption still remained. The remainder may be due to the Cl(-)/HCO3 (-) exchanger and Na(+)-Cl(-) cotransporter (NCC), since inhibitors for these transporters almost nullified the remaining water absorption. Quantitative PCR analysis revealed the presence of major proteins involved in water absorption; the NKCC2β and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCCβ genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2β was MI > PI, and that of NCCβ was MI < PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na(+)-K(+)-Cl(-) transport system governed by NKCC2β, but also regulates unknown ion transporters different from GN-insensitive SLC26A6 and NCC. A candidate is cystic fibrosis transmembrane conductance regulator Cl(-) channel, as demonstrated in mammals, but its expression is low in eel intestine, and its role may be minor, as indicated by the small effect of its inhibitors.

  5. Involvement of Concentrative Nucleoside Transporter 1 in Intestinal Absorption of Trifluridine Using Human Small Intestinal Epithelial Cells.

    PubMed

    Takahashi, Koichi; Yoshisue, Kunihiro; Chiba, Masato; Nakanishi, Takeo; Tamai, Ikumi

    2015-09-01

    TAS-102, which is effective for refractory metastatic colorectal cancer, is a combination drug of anticancer trifluridine (FTD; which is derived from pyrimidine nucleoside) and FTD-metabolizing enzyme inhibitor tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5. To evaluate the intestinal absorption mechanism of FTD, the uptake and transcellular transport of FTD by human small intestinal epithelial cell (HIEC) monolayer as a model of human intestinal epithelial cells was investigated. The uptake and membrane permeability of FTD by HIEC monolayers were saturable, Na(+) -dependent, and inhibited by nucleosides. These transport characteristics are mostly comparable with those of concentrative nucleoside transporters (CNTs). Moreover, the uptake of FTD by CNT1-expressing Xenopus oocytes was the highest among human CNT transporters. The obtained Km and Vmax values of FTD by CNT1 were 69.0 μM and 516 pmol/oocyte/30 min, respectively. The transcellular transport of FTD by Caco-2 cells, where CNT1 is heterologously expressed, from apical to basolateral side was greater than that by Mock cells. In conclusion, these results demonstrated that FTD exhibits high oral absorption by the contribution of human CNT1.

  6. Consensus hologram QSAR modeling for the prediction of human intestinal absorption.

    PubMed

    Moda, Tiago L; Andricopulo, Adriano D

    2012-04-15

    Consistent in silico models for ADME properties are useful tools in early drug discovery. Here, we report the hologram QSAR modeling of human intestinal absorption using a dataset of 638 compounds with experimental data associated. The final validated models are consistent and robust for the consensus prediction of this important pharmacokinetic property and are suitable for virtual screening applications.

  7. Intestinal Absorption of Fucoidan Extracted from the Brown Seaweed, Cladosiphon okamuranus

    PubMed Central

    Nagamine, Takeaki; Nakazato, Kyoumi; Tomioka, Satoru; Iha, Masahiko; Nakajima, Katsuyuki

    2014-01-01

    The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro. PMID:25546518

  8. Intestinal absorption of fucoidan extracted from the brown seaweed, Cladosiphon okamuranus.

    PubMed

    Nagamine, Takeaki; Nakazato, Kyoumi; Tomioka, Satoru; Iha, Masahiko; Nakajima, Katsuyuki

    2015-01-01

    The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro.

  9. Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance*

    PubMed Central

    Nelson, David W.; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-01-01

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. PMID:24784138

  10. Intestine-specific deletion of acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance.

    PubMed

    Nelson, David W; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-06-20

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2(-/-)) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism.

  11. Effect of different beta-adrenergic agonists on the intestinal absorption of galactose and phenylalanine.

    PubMed

    Díez-Sampedro, A; Pérez, M; Cobo, M T; Martínez, J A; Barber, A

    1998-08-01

    Nutrient transport across the mammalian small intestine is regulated by several factors, including intrinsic and extrinsic neural pathways, paracrine modulators, circulating hormones and luminal agents. Because beta-adrenoceptors seem to regulate gastrointestinal functions such as bicarbonate and acid secretion, intestinal motility and gastrointestinal mucosal blood flow, we have investigated the effects of different beta-adrenergic agonists on nutrient absorption by the rat jejunum in-vitro. When intestinal everted sacs were used the beta2-agonist salbutamol had no effect either on galactose uptake by the tissue or mucosal-to-serosal flux whereas mixed beta1- and beta2-agonists (isoproterenol and orciprenaline) and beta3-agonists (BRL 35135, Trecadrine, ICI 198157 and ZD 7114) inhibited galactose uptake and transfer of D-galactose from the mucosal-to-serosal media across the intestinal wall (although the inhibiting effects of isoproterenol and Trecadrine were not statistically significant). In intestinal everted rings both Trecadrine and BRL 35135 clearly reduced galactose uptake, the effect being a result of inhibition of the phlorizin-sensitive component. Total uptake of phenylalanine by the intestinal rings was also reduced by those beta3-adrenergic agonists. These results suggest that beta1- and beta3-adrenergic receptors could be involved in the regulation of intestinal active transport of sugars and amino acids. PMID:9751456

  12. Glucose sensing by waveguide-based absorption spectroscopy on a silicon chip

    PubMed Central

    Ryckeboer, E.; Bockstaele, R.; Vanslembrouck, M.; Baets, R.

    2014-01-01

    In this work, we demonstrate in vitro detection of glucose by means of a lab-on-chip absorption spectroscopy approach. This optical method allows label-free and specific detection of glucose. We show glucose detection in aqueous glucose solutions in the clinically relevant concentration range with a silicon-based optofluidic chip. The sample interface is a spiral-shaped rib waveguide integrated on a silicon-on-insulator (SOI) photonic chip. This SOI chip is combined with micro-fluidics in poly(dimethylsiloxane) (PDMS). We apply aqueous glucose solutions with different concentrations and monitor continuously how the transmission spectrum changes due to glucose. Based on these measurements, we derived a linear regression model, to relate the measured glucose spectra with concentration with an error-of-fitting of only 1.14 mM. This paper explains the challenges involved and discusses the optimal configuration for on-chip evanescent absorption spectroscopy. In addition, the prospects for using this sensor for glucose detection in complex physiological media (e.g. serum) is briefly discussed. PMID:24877021

  13. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced change in intestinal function and pathology: evidence for the involvement of arylhydrocarbon receptor-mediated alteration of glucose transportation

    SciTech Connect

    Ishida, Takumi; Kan-o, Shoko; Mutoh, Junpei; Takeda, Shuso; Ishii, Yuji; Hashiguchi, Isamu; Akamine, Akifumi; Yamada, Hideyuki . E-mail: yamada@xenoba.phar.kyushu-u.ac.jp

    2005-05-15

    Although numerous studies have been performed to clarify the mechanism(s) underlying the toxicological responses induced by dioxins, their effect on the intestine is less well understood. To address this issue, we examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the pathology and function of the intestine in arylhydrocarbon receptor (AhR)-sensitive (C57BL/6J) and -less-sensitive (DBA/2J) mice. A single oral administration of TCDD (100 {mu}g/kg) to C57BL/6J mice produced changes in villous structure and nuclear/cytoplasm ratio in the epithelial cells of the intestine. Furthermore, in an oral glucose tolerance test, the serum glucose level was significantly increased in the C57BL/6J mouse but not in the DBA/2J mouse by TCDD treatment. In agreement with this, the expression of intestinal mRNAs coding sodium-glucose co-transporter 1 (SGLT1) and glucose transporter type 2 were increased only in C57BL/6J mice by TCDD. The increase in the former transporter was also confirmed from its protein level. The glucose level in the intestinal contents is thought to be one of the factors contributing to SGLT1 induction. Concerning with this, the intestinal activity of sucrase and lactase was significantly increased only in C57BL/6J mice by TCDD. These results suggest that while TCDD produces initial damage to the intestinal epithelium, the tissues induce SGLT1 to facilitate the absorption of glucose, which is expected, at least partially, to combat the wasting syndrome induced by TCDD. The data provided here also suggest that AhR is involved in the mechanism of SGLT1 induction.

  14. Use of inverted intestinal sacs to assess the effect of gastrointestinal insult on carcinogen absorption.

    PubMed

    Capel, I D; Cosier, R S; Pinnock, M H; Williams, D C

    1981-01-01

    Rats were subjected to various forms of treatment in the manner likely to induce gastrointestinal insult. These and control animals were sacrificed and, using inverted sacs, the rate of absorption of either dimethylnitrosamine and benzo(a)pyrene determined. The gastrointestinal injury resulting from the differing treatments did not significantly affect the absorption of benzo(a)pyrene, whereas that of dimethylnitrosamine was significantly increased after each incubation time, most notably by alcohol pretreatment. The results demonstrate that intestinal damage increases the absorption of some carcinogens.

  15. Kinetics of D-glucose and L-leucine transport into sheep and pig intestinal brush border membrane vesicles.

    PubMed

    Wolffram, S; Eggenberger, E; Scharrer, E

    1986-01-01

    The kinetic parameters (Vmax, Kt) of Na+-dependent D-glucose transport into brush border membrane vesicles (BBMV) from sheep and pig jejunum were determined. Due to the fermentation of ingested carbohydrates in the rumen the small intestine of ruminants (sheep) has to absorb much less glucose than the small intestine of monogastric omnivores (pigs) or herbivores. Kinetic analysis of the concentration dependence of D-glucose transport revealed a ten-fold smaller Vmax value combined with a five times lower Kt value in sheep BBMV compared with pig BBMV. The Vmax value for L-leucine transport did not differ between the two species investigated, whereas the Kt value in the sheep exceeded that in the pig. It is concluded from these results that the mechanism for Na+-dependent D-glucose transport in ruminants is adapted to the small amounts of carbohydrates reaching the small intestine.

  16. Glucose-dependent insulinotropic polypeptide-mediated signaling pathways enhance apical PepT1 expression in intestinal epithelial cells.

    PubMed

    Coon, Steven D; Rajendran, Vazhaikkurichi M; Schwartz, John H; Singh, Satish K

    2015-01-01

    We have shown recently that glucose-dependent insulinotropic polypeptide (GIP), but not glucagon-like peptide 1 (GLP-1) augments H(+) peptide cotransporter (PepT1)-mediated peptide absorption in murine jejunum. While we observed that inhibiting cAMP production decreased this augmentation of PepT1 activity by GIP, it was unclear whether PKA and/or other regulators of cAMP signaling pathway(s) were involved. This study utilized tritiated glycyl-sarcosine [(3)H-glycyl-sarcosine (Gly-Sar), a relatively nonhydrolyzable dipeptide] uptake to measure PepT1 activity in CDX2-transfected IEC-6 (IEC-6/CDX2) cells, an absorptive intestinal epithelial cell model. Similar to our earlier observations with mouse jejunum, GIP but not GLP-1 augmented Gly-Sar uptake (control vs. +GIP: 154 ± 22 vs. 454 ± 39 pmol/mg protein; P < 0.001) in IEC-6/CDX2 cells. Rp-cAMP (a PKA inhibitor) and wortmannin [phosophoinositide-3-kinase (PI3K) inhibitor] pretreatment completely blocked, whereas neither calphostin C (a potent PKC inhibitor) nor BAPTA (an intracellular Ca(2+) chelator) pretreatment affected the GIP-augmented Gly-Sar uptake in IEC-6/CDX2 cells. The downstream metabolites Epac (control vs. Epac agonist: 287 ± 22 vs. 711 ± 80 pmol/mg protein) and AKT (control vs. AKT inhibitor: 720 ± 50 vs. 75 ± 19 pmol/mg protein) were shown to be involved in GIP-augmented PepT1 activity as well. Western blot analyses revealed that both GIP and Epac agonist pretreatment enhance the PepT1 expression on the apical membranes, which is completely blocked by wortmannin in IEC-6/CDX2 cells. These observations demonstrate that both cAMP and PI3K signaling pathways augment GIP-induced peptide uptake through Epac and AKT-mediated pathways in intestinal epithelial cells, respectively. In addition, these observations also indicate that both Epac and AKT-mediated signaling pathways increase apical membrane expression of PepT1 in intestinal absorptive epithelial cells.

  17. A preparation of perfused small intestine for the study of absorption in amphibia.

    PubMed

    Parsons, D S; Prichard, J S

    1968-09-01

    1. A preparation of amphibian small intestine perfused through its vascular system is described. Vascular perfusion with a bicarbonate Ringer solution containing a colloid is used to control the composition of the environment of the submucosal faces of the absorbing cells and to carry away for collection any material extruded from these cells. Oxygenation of the mucosal cells is derived primarily from fluid circulated through the intestinal lumen. The preparation exhibits physiological properties of transport for periods of up to 5 hr. After 5 hr perfusion the epithelial cells show no signs of gross cellular damage when examined either by light or by electron microscopy.2. The relationship between the hydrostatic pressure at the mesenteric artery and the rate of perfusion through the vascular bed is substantially linear. The pressure-flow relationships in the mesenteric bed, including an apparent ;critical closing pressure', are primarily determined by the hydrostatic pressure in the intestinal lumen. Alterations in the hydrostatic pressure in the intestinal lumen also change the relative proportions of the vascular infusate which appear in the portal venous effluent and in the fluid exuded from the serosal surface of the preparation (;sweat'). Hydrostatic distension pressures above about 10 cm H(2)O reduce the rate of collection of fluid from the portal vein and increase the rate of collection of ;sweat'.3. An increase in the rate of vascular perfusion increases the total rate of glucose appearance although the glucose concentrations in both the portal effluent and the ;sweat' are reduced.4. The glucose translocation rate is related in an alinear saturable fashion to the luminal concentration of glucose. By making a correction for metabolic loss of glucose during its passage through the intestinal cell, the relationship existing between the lumen concentration and the uptake of the sugar by the mucosal cells has been calculated. This relationship is found to fit

  18. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.

    PubMed

    Sekar, Revathi; Chow, Billy K C

    2014-08-01

    Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed.

  19. Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres

    PubMed Central

    Reineke, Joshua J.; Cho, Daniel Y.; Dingle, Yu-Ting; Morello, A. Peter; Jacob, Jules; Thanos, Christopher G.; Mathiowitz, Edith

    2013-01-01

    Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 µm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 µm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine. PMID:23922388

  20. Unique insights into the intestinal absorption, transit, and subsequent biodistribution of polymer-derived microspheres.

    PubMed

    Reineke, Joshua J; Cho, Daniel Y; Dingle, Yu-Ting; Morello, A Peter; Jacob, Jules; Thanos, Christopher G; Mathiowitz, Edith

    2013-08-20

    Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 µm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤ 5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 µm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine. PMID:23922388

  1. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice.

    PubMed

    Bura, Kanwardeep S; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A; Sawyer, Janet K; Shah, Ramesh; Wilson, Martha D; Dikkers, Arne; Tietge, Uwe J F; Collet, Xavier; Rudel, Lawrence L; Temel, Ryan E; Brown, J Mark

    2013-06-01

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  2. A Sensitive Medium-Throughput Method to Predict Intestinal Absorption in Humans Using Rat Intestinal Tissue Segments.

    PubMed

    Da Silva, Laís Cristina; Da Silva, Taynara Lourenço; Antunes, Alisson Henrique; Rezende, Kênnia Rocha

    2015-09-01

    A range of in vitro, ex vivo, and in vivo approaches are currently used for drug development. Highly predictive human intestinal absorption models remain lagging behind the times because of numerous variables concerning permeability through gastrointestinal tract in humans. However, there is a clear need for a drug permeability model early in the drug development process that can balance the requirements for high throughput and effective predictive potential. The present study developed a medium throughput screening Snapwell (MTS-Snapwell) ex vivo model to provide an alternative method to classify drug permeability. Rat small intestine tissue segments were mounted in commercial Snapwell™ inserts. Unidirectional drug transport (A-B) was measured by collecting samples at different time points. Viability of intestinal tissue segments was measured by examining transepithelial electric resistance (TEER) and phenol red and caffeine transport. As a result, the apparent permeability (Papp; ×10(-6) cm/s) was determined for atenolol (10.7 ± 1.2), caffeine (17.6 ± 3.1), cimetidine (6.9 ± 0.1), metoprolol (12.6 ± 0.7), theophylline (15.3 ± 1.6) and, ranitidine (3.8 ± 0.4). All drugs were classified in high/low permeability according to Biopharmaceutics Classification System showing high correlation with human data (r = 0.89). These findings showed a high correlation with human data (r = 0.89), suggesting that this model has potential predictive capacity for paracellular and transcellular passively absorbed molecules.

  3. Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

    PubMed

    Liang, Kai; Zhai, Shuiting; Zhang, Zhidong; Wang, Guoquan; Fu, Xiaoyang; Li, Tianxiao

    2016-07-01

    In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different. PMID:27592492

  4. Study on the small intestine absorptive kinetics characters of tanshinol and protocatechualdehyde of Salvia miltiorrhiza extracts in rats in vivo.

    PubMed

    Liang, Kai; Zhai, Shuiting; Zhang, Zhidong; Wang, Guoquan; Fu, Xiaoyang; Li, Tianxiao

    2016-07-01

    In order to provide scientific basis for clinical selection of drugs, to compare and analyze the effective constitutes and the intestinal absorption in vivo in rats of the compound salvia tablets and compound salvia dropping pills (taken as the representatives). Determine the contents of tanshinol, protocatechuic aldehyde, salvianolic acid B and tanshinone II A, cryptotanshinone, ginseng saponin Rg1 and Rb1 in the compound salvia tablets and compound salvia dropping pills by High Performance Liquid Chromatography (HPLC). The intestinal absorption condition of the tanshinol, protocatechuic aldehyde, salvianolic acid B of the compound salvia tablets and compound salvia dropping pills in rats were detected by intestinal perfusion experiment. Only the intake of protocatechuic aldehyde in the compound salvia tablets was higher than in the compound dropping pills, the intake of the other 6 effective constitutes were all lower than in the compound dropping pills. The intestinal absorption of protocatechuic aldehyde was rather complete, while the intestinal absorption of tanshinol and salvianolic acid B were not significant. The duodenum was the main absorption region of these three components. The absorption of protocatechuic aldehyde was different in different regions of the intestines. Each intake of the effective constitutes in the tablets and dropping pills were significantly different, and the rat intestinal absorption of part of the components were different.

  5. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review

    PubMed Central

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-01-01

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. PMID:26370977

  6. Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells--A Review.

    PubMed

    Kamiloglu, Senem; Capanoglu, Esra; Grootaert, Charlotte; Van Camp, John

    2015-09-08

    Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells.

  7. Synthesis, characterization and in situ intestinal absorption of different molecular weight scutellarin-PEG conjugates.

    PubMed

    Zhou, Qingsong; Jiang, Xuehua; Li, Kejia; Fan, Xingxing

    2006-08-01

    Highly water soluble esters of scutellarin with different molecular weight polyethylene glycol (PEG) were synthesized. The physicochemical properties, the stabilities under different conditions and the in situ intestinal absorption of the conjugates in rats were investigated. By PEG modification, greatly increased water solubility and a desirable partition coefficient were obtained. These compounds act as prodrugs i.e. breakdown occurrs in a predictable fashion: in vitro, the t1/2 of them in PBS buffer at pH 7.4 was above 12 h (37 degrees C), while in plasma a more rapid breakdown was observed (t1/2 1.5-3 h). PEGylation could enhance the absorption of scutellarin in rat intestine, and scutellarin, its PEG conjugates are absorbed through intestine mainly via passive transport. When the molecular weight of PEG increased from 200 to 1000 Da, the absorption of the conjugates decreased accordingly. The range of PEG molecular weight used for the PEGylation of scutellarin was about 400-1000 Da based on considerations of the yield, the stability and the absorption.

  8. Assessment of intestinal absorption of trace metals in humans by means of stable isotopes.

    PubMed

    Werner, E; Roth, P; Höllriegl, V; Hansen, Ch; Kaltwasser, J P; Giussani, A; Cantone, M C; Greim, H; Zilker, T; Felgenhauer, N

    2002-03-01

    This study is aimed to demonstrate the feasibility of stable isotopes for the assessment of reliable data on fractional intestinal absorption of trace metals in healthy humans. Among the various methods available, the double isotope technique, i.e. one isotope given orally together with the test substance to be investigated and another isotope injected intravenously to correct for retention and endogenous excretion of the particular trace metal, provides quantitative figures of intestinal absorption at reasonable expenses with regard to costs for materials and number of samples to be evaluated. The trace metals exemplarily included in this study, i.e. iron, cobalt and molybdenum show diverging relations between absorbed fractions and amounts administered which are indicative for different regulatory mechanisms of their body content. Food ligands influence the fractional absorption significantly so that the uptake from a composite meal cannot be derived from results on uptake from particular foodstuffs. Therefore, validated data on the behaviour of intestinal absorption will significantly contribute to a better understanding of human trace metal metabolism.

  9. Intestinal absorption of dietary fat from a liquid diet perfused in rats at a submaximum level

    SciTech Connect

    Simko, V.; Kelley, R.E.

    1988-02-01

    The small intestine of rats was perfused in vivo for 2 h with a nutritionally complete liquid diet (68% calories from fat as corn oil). As the perfusion increased from 106 mg/2 h, the intestinal disappearance of the /sup 14/C-triolein marker remained proportional to the load up to 2359 mg fat/2 h. Despite a decrease in absorption from 70 to 17%, this represents a very large fat intake. Fat absorption improved when medium-chain triglycerides or octanoic acid replaced corn oil (both p less than 0.01). Linoleic acid was absorbed from the diet less than corn oil (p less than 0.01). Dry ox bile reduced fat absorption (p less than 0.05); lipase and an antacid had no effect. Corn oil perfused alone was absorbed better than from the diet (p less than 0.01). Data with /sup 14/C-triolein was confirmed by dry-weight disappearance of the diet and by net intestinal water balance. Usual feeding underutilizes a large reserve for fat absorption. This reserve should be considered in therapeutic nutrition.

  10. Whey protein hydrolysates enhance water absorption in the perfused small intestine of anesthetized rats.

    PubMed

    Ito, Kentaro; Yamaguchi, Makoto; Noma, Teruyuki; Yamaji, Taketo; Itoh, Hiroyuki; Oda, Munehiro

    2016-08-01

    We evaluated the effect of whey protein hydrolysates (WPH) on the water absorption rate in the small intestine using a rat small intestine perfusion model. The rate was significantly higher with 5 g/L WPH than with 5 g/L soy protein hydrolysates or physiological saline (p < 0.05). WPH dose-dependently increased the water absorption rate in the range of 1.25-10.0 g/L. WPH showed a significantly higher rate than an amino acid mixture whose composition was equal to that of WPH (p < 0.05). The addition of 4-aminomethylbenzoic acid, an inhibitor of PepT1, significantly suppressed WPH's enhancement of water absorption (p < 0.05). The rate of water absorption was significantly correlated with that of peptides/amino acids absorption in WPH (r = 0.82, p < 0.01). These data suggest that WPH have a high water absorption-promoting effect, to which PepT1 contributes.

  11. Studies on different iron source absorption by in situ ligated intestinal loops of broilers.

    PubMed

    Jia, Y F; Jiang, M M; Sun, J; Shi, R B; Liu, D S

    2015-02-01

    The objective of this study was to investigate the iron source absorption in the small intestine of broiler. In situ ligated intestinal loops of 70 birds were poured into one of seven solutions, including inorganic iron (FeSO4, Fe2(SO4)3), organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)), the mixtures (FeSO4 with glycine (Fe+Gly(II)), Fe2(SO4)3 with glycine (Fe+Gly(III)), and no Fe source (control). The total volume of 3-mL solution (containing 1 mg of elemental Fe) was injected into intestinal loops, and then 120-min incubation was performed. Compared with inorganic iron groups, in which higher FeSO4 absorption than Fe2(SO4)3 was observed, supplementation with organic Fe glycine chelate significantly increased the Fe concentration in the duodenum and jejunum (P < 0.05), however, decreased DMT1 and DcytB messenger RNA (mRNA) levels (P < 0.05). Organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)) increased serum iron concentration (SI), compared with inorganic 3 valence iron groups (Fe2(SO4)3 and Fe+Gly(III)) (P < 0.05); moreover, lower TIBC value was observed for the chelate (P < 0.05); however, mixture of inorganic iron and glycine did not have a positive role at DMT1 and DcytB mRNA levels, SI and Fe concentrations in the small intestine. Those results indicated that the absorption of organic Fe glycine chelate was more effective than that of inorganic Fe, and the orders of iron absorption in the small intestine were: Fe-Gly(II), Fe-Gly(III) > FeSO4, Fe+Gly(II) > Fe2(SO4)3, Fe+Gly(III). Additionally, the simple mixture of inorganic iron and glycine could not increase Fe absorption, and the duodenum was the main site of Fe absorption in the intestines of broilers and the ileum absorbed iron rarely.

  12. Chronic and selective inhibition of basolateral membrane Na-K-ATPase uniquely regulates brush border membrane Na absorption in intestinal epithelial cells

    PubMed Central

    Manoharan, Palanikumar; Gayam, Swapna; Arthur, Subha; Palaniappan, Balasubramanian; Singh, Soudamani; Dick, Gregory M.

    2015-01-01

    Na-K-ATPase, an integral membrane protein in mammalian cells, is responsible for maintaining the favorable intracellular Na gradient necessary to promote Na-coupled solute cotransport processes [e.g., Na-glucose cotransport (SGLT1)]. Inhibition of brush border membrane (BBM) SGLT1 is, at least in part, due to the diminished Na-K-ATPase in villus cells from chronically inflamed rabbit intestine. The aim of the present study was to determine the effect of Na-K-ATPase inhibition on the two major BBM Na absorptive pathways, specifically Na-glucose cotransport and Na/H exchange (NHE), in intestinal epithelial (IEC-18) cells. Na-K-ATPase was inhibited using 1 mM ouabain or siRNA for Na-K-ATPase-α1 in IEC-18 cells. SGLT1 activity was determined as 3-O-methyl-d-[3H]glucose uptake. Na-K-ATPase activity was measured as the amount of inorganic phosphate released. Treatment with ouabain resulted in SGLT1 inhibition at 1 h but stimulation at 24 h. To further characterize this unexpected stimulation of SGLT1, siRNA silencing was utilized to inhibit Na-K-ATPase-α1. SGLT1 activity was significantly upregulated by Na-K-ATPase silencing, while NHE3 activity remained unaltered. Kinetics showed that the mechanism of stimulation of SGLT1 activity was secondary to an increase in affinity of the cotransporter for glucose without a change in the number of cotransporters. Molecular studies demonstrated that the mechanism of stimulation was not secondary to altered BBM SGLT1 protein levels. Chronic and direct silencing of basolateral Na-K-ATPase uniquely regulates BBM Na absorptive pathways in intestinal epithelial cells. Specifically, while BBM NHE3 is unaffected, SGLT1 is stimulated secondary to enhanced affinity of the cotransporter. PMID:25652450

  13. Chronic and selective inhibition of basolateral membrane Na-K-ATPase uniquely regulates brush border membrane Na absorption in intestinal epithelial cells.

    PubMed

    Manoharan, Palanikumar; Gayam, Swapna; Arthur, Subha; Palaniappan, Balasubramanian; Singh, Soudamani; Dick, Gregory M; Sundaram, Uma

    2015-04-15

    Na-K-ATPase, an integral membrane protein in mammalian cells, is responsible for maintaining the favorable intracellular Na gradient necessary to promote Na-coupled solute cotransport processes [e.g., Na-glucose cotransport (SGLT1)]. Inhibition of brush border membrane (BBM) SGLT1 is, at least in part, due to the diminished Na-K-ATPase in villus cells from chronically inflamed rabbit intestine. The aim of the present study was to determine the effect of Na-K-ATPase inhibition on the two major BBM Na absorptive pathways, specifically Na-glucose cotransport and Na/H exchange (NHE), in intestinal epithelial (IEC-18) cells. Na-K-ATPase was inhibited using 1 mM ouabain or siRNA for Na-K-ATPase-α1 in IEC-18 cells. SGLT1 activity was determined as 3-O-methyl-D-[(3)H]glucose uptake. Na-K-ATPase activity was measured as the amount of inorganic phosphate released. Treatment with ouabain resulted in SGLT1 inhibition at 1 h but stimulation at 24 h. To further characterize this unexpected stimulation of SGLT1, siRNA silencing was utilized to inhibit Na-K-ATPase-α1. SGLT1 activity was significantly upregulated by Na-K-ATPase silencing, while NHE3 activity remained unaltered. Kinetics showed that the mechanism of stimulation of SGLT1 activity was secondary to an increase in affinity of the cotransporter for glucose without a change in the number of cotransporters. Molecular studies demonstrated that the mechanism of stimulation was not secondary to altered BBM SGLT1 protein levels. Chronic and direct silencing of basolateral Na-K-ATPase uniquely regulates BBM Na absorptive pathways in intestinal epithelial cells. Specifically, while BBM NHE3 is unaffected, SGLT1 is stimulated secondary to enhanced affinity of the cotransporter.

  14. [Coupling of protease activity and sodium loading with intestinal absorption of amino acids].

    PubMed

    Basova, N A; Markov, Iu G; Berzinia, N I

    2005-09-01

    Membrane-bound serine proteases to play a certain role in activation of sodium transport in epithelial cells. To were found explain the protease activity and sodium-dependent L-tryptophan transport across chicken small intestine interaction, four experiments were conducted. One hundred chicks were fed diets that contained 0; 0.3; 3 or 6% of supplemental NaCl and were given distillated water ad libitum. Signs of salt toxicity observed were as follows: a decreased body weight, increased heart and kidney weights, formation of secondary lysosomes in enterocytes and lymphocytes. Such chickens were in the state of negative nitrogen balance. Intestinal absorption of L-tryptophan correlated with mucosal protease activity during increased dietary sodium chloride intake. Recent in vitro and in vivo experiments indicate that enterocyte proteases may be of critical importance in activation of sodium-dependent intestinal transporters for L-tryptophan.

  15. Intestinal absorption of triglyceride and vitamin D3 in aged and young rats

    SciTech Connect

    Holt, P.R.; Dominguez, A.A.

    1981-12-01

    (3H)Trioleyl glycerol (TO) and (14C)vitamin D3 were perfused intraduodenally for 5 hr in aged (19-21 months) and young adult (4-5 months) Sprague-Dawley rats. The rate of intestinal uptake from the gastrointestinal lumen and transport into the body of these lipids were decreased in the aged animals. Since the distribution of TO lipolytic products in the lumen was unchanged, reduced intestinal uptake rate probably occurred at the mucosal membrane. Furthermore, in the aged rats, the rate of transintestinal transport of both trioleyl glycerol and vitamin D3 was impaired. No evidence for impaired mucosal TO reesterification or for accumulation of vitamin D3 metabolites was found, suggesting that intestinal lipid accumulation resulted from a defect in lipoprotein assembly or in discharge from the mucosal cell. Impaired absorption of lipids may contribute to malnutrition and osteopenia of advancing age.

  16. Unconjugated bilirubin and the bile from light exposed Gunn rats inhibit intestinal water and electrolyte absorption.

    PubMed Central

    Guandalini, S; Fasano, A; Albini, F; Marchesano, G; Nocerino, A; De Curtis, M; Rubaltelli, F F; Pettenazzo, A; Rubino, A

    1988-01-01

    Jaundiced babies undergoing phototherapy often develop diarrhoea. The cause of it is still uncertain. Increasing evidence supports a role of a secretory mechanism for the diarrhoea. We therefore studied the effects of bile from congenitally jaundiced rats undergoing phototherapy and of unconjugated bilirubin on rat small intestine in vivo and in vitro. Results suggest that: (1) the bile from homozygous Gunn rats under phototherapy has an anti-absorptive effect when tested in the perfused jejunum of normal Wistar rats; (2) unconjugated bilirubin has a dose dependent secretory effect on the intestinal transport of water and electrolytes, when tested in the same system. Alteration of cyclic AMP or cyclic GMP, known intracellular mediators of secretion, was not observed. We conclude that free bilirubin is an intestinal secretagogue acting by an as yet unknown mechanism, that may mediate the secretory type of diarrhoea in jaundiced neonates undergoing phototherapy. PMID:3356369

  17. Determination of Site of Absorption of Propranolol in Rat Gut Using In Situ Single-Pass Intestinal Perfusion

    PubMed Central

    Nagare, N.; Damre, Anagha; Singh, K. S.; Mallurwar, S. R.; Iyer, Seethalakshmi; Naik, A.; Chintamaneni, Meena

    2010-01-01

    Previously, permeability and site of intestinal absorption of propranolol have been reported using the Ussing chamber. In the present study, the utility of Single-Pass Intestinal Perfusion to study permeability and site of intestinal absorption of propranolol was evaluated in rats. Drug permeability in different regions of rat intestine viz. duodenum, jejunum, ileum and colon was measured. Propranolol (30 μg/ml) solution was perfused in situ in each intestinal segment of rats. Effective permeability (Peff) of propranolol in each segment was calculated and site of absorption was determined. The Peff of propranolol in rat duodenum, jejunum, ileum and colon was calculated to be 0.3316×10-4 cm/s, 0.4035×10-4cm/s, 0.5092×10-4 cm/s and 0.7167×10-4 cm/s, respectively. The above results suggest that permeability of propranolol was highest through colon compared to other intestinal sites, which is in close agreement to that reported previously. In conclusion, in situ single pass intestinal perfusion can be used effectively to study intestinal permeability as well as site of intestinal absorption of compounds in rats. PMID:21694996

  18. Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion.

    PubMed

    Nagare, N; Damre, Anagha; Singh, K S; Mallurwar, S R; Iyer, Seethalakshmi; Naik, A; Chintamaneni, Meena

    2010-09-01

    Previously, permeability and site of intestinal absorption of propranolol have been reported using the Ussing chamber. In the present study, the utility of Single-Pass Intestinal Perfusion to study permeability and site of intestinal absorption of propranolol was evaluated in rats. Drug permeability in different regions of rat intestine viz. duodenum, jejunum, ileum and colon was measured. Propranolol (30 μg/ml) solution was perfused in situ in each intestinal segment of rats. Effective permeability (Peff) of propranolol in each segment was calculated and site of absorption was determined. The Peff of propranolol in rat duodenum, jejunum, ileum and colon was calculated to be 0.3316×10(-4) cm/s, 0.4035×10(-4)cm/s, 0.5092×10(-4) cm/s and 0.7167×10(-4) cm/s, respectively. The above results suggest that permeability of propranolol was highest through colon compared to other intestinal sites, which is in close agreement to that reported previously. In conclusion, in situ single pass intestinal perfusion can be used effectively to study intestinal permeability as well as site of intestinal absorption of compounds in rats.

  19. A novel mechanism for the promotion of quercetin glycoside absorption by megalo α-1,6-glucosaccharide in the rat small intestine.

    PubMed

    Shinoki, Aki; Lang, Weeranuch; Thawornkuno, Charin; Kang, Hee-Kwon; Kumagai, Yuya; Okuyama, Masayuki; Mori, Haruhide; Kimura, Atsuo; Ishizuka, Satoshi; Hara, Hiroshi

    2013-01-15

    The presence of an α-1,6-glucosaccharide enhances absorption of water-soluble quercetin glycosides, a mixture of quercetin-3-O-β-d-glucoside (Q3G, 31.8%), mono (23.3%), di (20.3%) and more d-glucose adducts with α-1,4-linkage to a d-glucose moiety of Q3G, in a ligated small intestinal loop of anesthetized rats. We prepared α-1,6-glucosaccharides with different degrees of polymerization (DP) enzymatically and separated them into a megalo-isomaltosaccharide-containing fraction (M-IM, average DP=11.0) and an oligo-isomaltosaccharide-containing fraction (O-IM, average DP=3.6). Luminal injection of either saccharide fraction promoted the absorption of total quercetin-derivatives from the small intestinal segment and this effect was greater for M-IM than O-IM addition. M-IM also increased Q3G, but not the quercetin aglycone, concentration in the water-phase of the luminal contents more strongly than O-IM. The enhancement of Q3G solubilization in the luminal contents may be responsible for the increases in the quercetin glucoside absorption promoted by α-1,6-glucosaccharides, especially that by M-IM. These results suggest that the ingestion of α-1,6-glucosaccharides promotes Q3G bioavailability.

  20. Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms.

    PubMed

    Subramanya, Sandeep B; Subramanian, Veedamali S; Kumar, Jeyan S; Hoiness, Robert; Said, Hamid M

    2011-03-01

    The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5'-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5'-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding.

  1. Calorie Restriction Increases P-Glycoprotein and Decreases Intestinal Absorption of Digoxin in Mice.

    PubMed

    Renaud, Helen J; Klaassen, Curtis D; Csanaky, Iván L

    2016-03-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [(3)H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [(3)H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum-fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance.

  2. Novel approach for non-invasive glucose sensing using vibrational contrast CD absorption measurements (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yakovlev, Vladislav V.; Tovar, Carlos; Hokr, Brett; Petrov, Georgi I.

    2016-03-01

    Noninvasive glucose sensing is a Holy Grail of diabetes mellitus management. Unfortunately, despite a number of innovative concepts and a long history of continuous instrumental improvements, the problem remains largely unsolved. Here we propose and experimentally demonstrate the first successful implementation of a novel strategy based on vibrational overtone circular dichroism absorption measurements. Such an approach uses a short-wavelength infrared excitation (1000-2000 nm), which takes the advantage of lower light scattering and intrinsic chemical contrast provided by the chemical structure of D-glucose molecule. We model the propagation of circular polarized light in scattering medium using Monte Carlo simulations to show the feasibility of such approach in turbid medium and demonstrate the proof of principle using optical detection. We also investigate the possibility of using ultrasound detection through circular dichroism absorption measurements to achieve simple and sensitive glucose monitoring.

  3. Evaluation of chromatographic descriptors for the prediction of gastro-intestinal absorption of drugs.

    PubMed

    Deconinck, E; Ates, H; Callebaut, N; Van Gyseghem, E; Vander Heyden, Y

    2007-01-01

    The use of chromatographic descriptors in QSAR was evaluated. Therefore, retentions were measured on an immobilized artificial membrane system, 2 micellar liquid chromatography systems and 17 orthogonal or disimilar reversed-phase liquid chromatographic systems. It was investigated whether it was possible to model gastro-intestinal absorption as a function of chromatographic retentions applying two linear and one non-linear multivariate modeling technique. In a second step it was evaluated if models built with theoretical descriptors could be improved by adding the measured retention factors to the data set of descriptive variables. It was seen that gastro-intestinal absorption could be modelled in function of chromatographic retention using the non-linear modeling technique multivariate adaptive regression splines (MARS). The best models were obtained using a combination of theoretical and chromatographic descriptors with MARS as modeling technique.

  4. An analytical solution for the model of drug distribution and absorption in small intestine

    NASA Astrophysics Data System (ADS)

    Mingyu, Xu

    1990-11-01

    According to the physiological and anatomical characteristics of small intestine, neglecting the effect of its motility on the distribution and absorption of drug and nutrient, Y. Miyamoto et al.[1] proposed a model of two-dimensional laminar flow in a circular porous tube with permeable wall and calculated the concentration profile of drug by numerical analysis. In this paper, we give a steady state analytical solution of the above model including deactivation term. The obtained results are in agreement with the results of their numerical analysis. Moreover the analytical solution presented in this paper reveals the relation among the physiological parameters of the model and describes the basic absorption rule of drug and nutrient through the intestinal wall and hence provides a theoretical basis for determining the permeability and reflection coefficient through in situ experiments.

  5. Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

    USGS Publications Warehouse

    Serafin, J.A.

    1984-01-01

    Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique. bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards. Mallards absorbed less dieldrin and mercury than black-crowned night-herons. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

  6. The influence of lactation on L-proline absorption from small intestine in the albino rat.

    PubMed

    Datta, U; Sharma, R K

    1985-01-01

    Intestinal absorption of L-proline was studied in control and lactating rats from jejunum and ileum by in vivo method and presented per unit dry weight and per unit length of the respective segment. L-proline absorption was found to be significantly reduced in lactating animals as compared to the virgin controls. The results were discussed in light of serosal to mucosal ratio. By in vitro method also jejunal and ileal uptake of L-proline were found to be significantly reduced in lactating animals as compared to the virgin controls.

  7. The relevance of the intestinal crypt and enterocyte in regulating iron absorption.

    PubMed

    Oates, Phillip S

    2007-11-01

    Rigorous regulation of iron absorption is required to meet the requirements of the body and to limit excess iron accumulation that can produce oxidative stress. Regulation of iron absorption is controlled by hepcidin and probably by the crypt program. Hepcidin is a humoral mediator of iron absorption that interacts with the basolateral transporter, ferroportin. High levels of hepcidin reduce iron absorption by targeting ferroportin to lysosomes for destruction. It is also proposed that ferroportin is expressed on the apical membrane and coordinates with ferroportin-hepcidin derived from the basal surface to modulate the uptake phase of iron absorption. The crypt program suggests that as crypt cells differentiate and migrate into the absorptive zone they absorb iron from the diet at levels inverse to the amount of iron taken up from transferrin. Under most circumstances, intestinal iron absorption is controlled at multiple levels that lead to hepcidin/ferroportin modulation of the enterocyte labile iron pool (LIP). It is likely that transcription of iron transport proteins involved in the apical and basolateral transport of iron are differentially regulated by separate LIPs. Iron-responsive protein (IRP) 1 and IRP2 do not appear to play a significant role in the expression of iron transport proteins, although IRP2 regulates L- and H-ferritin expression. Despite the importance of hepcidin, there is evidence of hepcidin-independent regulation of iron absorption possibly involving haemojuvelin (HJV) and neogenin, which may be up-regulated during ineffective erythropoiesis.

  8. Effects of a single dose of menadione on the intestinal calcium absorption and associated variables.

    PubMed

    Marchionatti, Ana M; Díaz de Barboza, Gabriela E; Centeno, Viviana A; Alisio, Arturo E; Tolosa de Talamoni, Nori G

    2003-08-01

    The effect of a single large dose of menadione on intestinal calcium absorption and associated variables was investigated in chicks fed a normal diet. The data show that 2.5 micro mol of menadione/kg of b.w. causes inhibition of calcium transfer from lumen-to-blood within 30 min. This effect seems to be related to oxidative stress provoked by menadione as judged by glutathione depletion and an increment in the total carbonyl group content produced at the same time. Two enzymes presumably involved in calcium transcellular movement, such as alkaline phosphatase, located in the brush border membrane, and Ca(2+)- pump ATPase, which sits in the basolateral membrane, were also inhibited. The enzyme inhibition could be due to alterations caused by the appearance of free hydroxyl groups, which are triggered by glutathione depletion. Addition of glutathione monoester to the duodenal loop caused reversion of the menadione effect on both intestinal calcium absorption and alkaline phosphatase activity. In conclusion, menadione shifts the balance of oxidative and reductive processes in the enterocyte towards oxidation causing deleterious effects on intestinal Ca(2+) absorption and associated variables, which could be prevented by administration of oral glutathione monoester. PMID:12948877

  9. Use of everted intestinal rings for in vitro examination of oral absorption potential.

    PubMed

    Leppert, P S; Fix, J A

    1994-07-01

    The ability to predict in vivo oral absorption potential based on ex vivo screening in an everted intestinal ring model was examined. In vitro drug accumulation in cross sectional rings of everted rat jejunum was determined with 12 compounds whose in vivo absorptions (as distinct from bioavailabilities) are well characterized. The compounds examined ranged from well- to poorly-absorbed and included compounds absorbed by active and passive mechanisms. The effects of drug concentration, pH, cosolvents, and tissue origin site on drug accumulation were determined. Light microscopic observation indicated that the mucosal tissue remained intact up to 3 h after the intestine was excised. Accumulations of two nonabsorbable markers were also determined as measures of tissue integrity. A strong correlation (slope = 23 pmol/mg of tissue weight per percent oral absorption, r2 = 0.9430 by linear regression analysis) of in vitro uptake into everted rings from a 10 mM drug solution versus the known in vivo bioavailability for each compound was observed. These results indicated that under appropriate conditions, in vitro uptake of drug by the everted intestinal ring model closely paralleled known in vivo bioavailability and was relatively independent of pH, cosolvent, and tissue origin.

  10. The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1.

    PubMed

    Li, Pei-Shan; Fu, Zhen-Yan; Zhang, Ying-Yu; Zhang, Jin-Hui; Xu, Chen-Qi; Ma, Yi-Tong; Li, Bo-Liang; Song, Bao-Liang

    2014-01-01

    Hypercholesterolemia, typically due to excessive cholesterol uptake, is a major risk factor for cardiovascular disease, which is responsible for ∼50% of all deaths in developed societies. Although it has been shown that intestinal cholesterol absorption is mediated by vesicular endocytosis of the Niemann-Pick C1-like 1 (NPC1L1) protein, the mechanism of sterol-stimulated NPC1L1 internalization is still mysterious. Here, we identified an endocytic peptide signal, YVNXXF (where X stands for any amino acid), in the cytoplasmic C-terminal tail of NPC1L1. Cholesterol binding on the N-terminal domain of NPC1L1 released the YVNXXF-containing region of NPC1L1 from association with the plasma membrane and enabled Numb binding. We also found that Numb, a clathrin adaptor, specifically recognized this motif and recruited clathrin for internalization. Disrupting the NPC1L1-Numb interaction decreased cholesterol uptake. Ablation of Numb in mouse intestine significantly reduced dietary cholesterol absorption and plasma cholesterol level. Together, these data show that Numb is a pivotal protein for intestinal cholesterol absorption and may provide a therapeutic target for hypercholesterolemia.

  11. Calcium absorption in rat large intestine in vivo: availability of dietary calcium

    SciTech Connect

    Ammann, P.; Rizzoli, R.; Fleisch, H.

    1986-07-01

    Calcium absorption in the large intestine of the rat was investigated in vivo. After a single injection of /sup 45/CaCl/sub 2/ into the cecum, 26.0 +/- 2.5% (mean +/- SE, n = 9) of the /sup 45/CaCl/sub 2/ injected disappeared. This absorption was modulated by 1,25-dihydroxyvitamin D3, increased to 64.0 +/- 4.2% under a low-Ca diet, and increased under low-Pi diet. In contrast, when the difference of nonradioactive Ca in the cecal content and the feces was measured, only 4.1 +/- 4.6% (not significant) was absorbed. Secretion of intravenously injected /sup 45/Ca into the lumen was small and not altered by any of the conditions tested. When cecum contents were placed into duodenal tied loops, 14 +/- 6.2% were absorbed in situ when /sup 45/Ca was given orally, whereas when /sup 45/Ca was directly added to the content 35.6 +/- 4.6% were absorbed (P less than 0.02). These results indicate that the large intestine has an important vitamin D-dependent Ca absorptive system detectable if /sup 45/Ca is injected into the cecum. However, it is not effective in vivo because the Ca arriving in the large intestine appears to be no longer in an absorbable form.

  12. Effects of a single dose of menadione on the intestinal calcium absorption and associated variables.

    PubMed

    Marchionatti, Ana M; Díaz de Barboza, Gabriela E; Centeno, Viviana A; Alisio, Arturo E; Tolosa de Talamoni, Nori G

    2003-08-01

    The effect of a single large dose of menadione on intestinal calcium absorption and associated variables was investigated in chicks fed a normal diet. The data show that 2.5 micro mol of menadione/kg of b.w. causes inhibition of calcium transfer from lumen-to-blood within 30 min. This effect seems to be related to oxidative stress provoked by menadione as judged by glutathione depletion and an increment in the total carbonyl group content produced at the same time. Two enzymes presumably involved in calcium transcellular movement, such as alkaline phosphatase, located in the brush border membrane, and Ca(2+)- pump ATPase, which sits in the basolateral membrane, were also inhibited. The enzyme inhibition could be due to alterations caused by the appearance of free hydroxyl groups, which are triggered by glutathione depletion. Addition of glutathione monoester to the duodenal loop caused reversion of the menadione effect on both intestinal calcium absorption and alkaline phosphatase activity. In conclusion, menadione shifts the balance of oxidative and reductive processes in the enterocyte towards oxidation causing deleterious effects on intestinal Ca(2+) absorption and associated variables, which could be prevented by administration of oral glutathione monoester.

  13. Intestinal absorption, organ distribution, and urinary excretion of the rare sugar D-psicose

    PubMed Central

    Tsukamoto, Ikuko; Hossain, Akram; Yamaguchi, Fuminori; Hirata, Yuko; Dong, Youyi; Kamitori, Kazuyo; Sui, Li; Nonaka, Machiko; Ueno, Masaki; Nishimoto, Kazuyuki; Suda, Hirofumi; Morimoto, Kenji; Shimonishi, Tsuyoshi; Saito, Madoka; Song, Tao; Konishi, Ryoji; Tokuda, Masaaki

    2014-01-01

    Background The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. Methods This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of 14C-labeled D-psicose or glucose intravenously to C3H mice. Results Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 μg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of 14C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. Conclusion D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal

  14. Intestinal absorption and biomagnification of organic contaminants in fish, wildlife, and humans.

    PubMed

    Kelly, Barry C; Gobas, Frank A P C; McLachlan, Michael S

    2004-10-01

    Methods for the regulatory assessment of the bioaccumulation potential of organic chemicals are founded on empirical measurements and mechanistic models of dietary absorption and biomagnification. This study includes a review of the current state of knowledge regarding mechanisms and models of intestinal absorption and biomagnification of organic chemicals in organisms of aquatic and terrestrial food chains and also includes a discussion of the implications of these models for assessing the bioaccumulation potential of organic chemicals. Four mechanistic models, including biomass conversion, digestion or gastrointestinal magnification, micelle-mediated diffusion, and fat-flush diffusion, are evaluated. The models contain many similarities and represent an evolution in understanding of chemical bioaccumulation processes. An important difference between the biomagnification models is whether intestinal absorption of an ingested contaminant occurs solely via passive molecular diffusion through serial resistances or via facilitated diffusion that incorporates an additional advective transport mechanism in parallel (i.e., molecular ferrying within gastrointestinal micelles). This difference has an effect on the selection of physicochemical properties that best anticipate the bioaccumulative potential of commercial chemicals in aquatic and terrestrial food chains. Current regulatory initiatives utilizing Kow threshold criteria to assess chemical bioaccumulation potential are shown to be unable to identify certain bioaccumulative substances in air-breathing animals. We urge further research on dietary absorption and biomagnification of organic chemicals to develop better models for assessing the bioaccumulative nature of organic chemicals. PMID:15511095

  15. In vivo application of chitosan to facilitate intestinal acyclovir absorption in rats.

    PubMed

    Masuda, Ayumi; Goto, Yuko; Kurosaki, Yuji; Aiba, Tetsuya

    2012-07-01

    The effect of chitosan on the intestinal absorption of acyclovir (ACV) was evaluated in rats, and factors influencing its facilitative effect on the ACV absorption were examined. When ACV solution containing 1% chitosan with an average molecular weight of 150 kDa was administered into the upper jejunum, a significant increase in the plasma ACV concentration was observed, with the peak ACV concentration being eight times greater than that observed with the chitosan-free solution. The chitosan-free ACV solution, whose viscosity was adjusted to remain unchanged with polyethylene glycol, did not cause an increase in the plasma concentration, and neither did the chitosan-free solutions substitutionally containing low molecular cationic compounds, triethanolamine and kanamycin. When chitosan was digested with chitosanase to shorten its polycationic polysaccharide structure, chitosan subjected to 150-min digestion retained its facilitative effect on ACV absorption, but that subjected to 420-min digestion no longer caused facilitation, in which its average molecular weight was reduced to around 10 kDa. It is therefore indicated that intestinal ACV absorption can be facilitated with chitosan, and that it is necessary for chitosan to have a certain length of polycationic polysaccharide structure to exert such facilitation.

  16. Influence of protein composition and hydrolysis method on intestinal absorption of protein in man.

    PubMed

    Keohane, P P; Grimble, G K; Brown, B; Spiller, R C; Silk, D B

    1985-09-01

    An intestinal perfusion technique has been used in normal human subjects to investigate the influence that starter protein composition and hydrolysis procedure have on absorption of amino acid residues from partial enzymic hydrolysates of whole protein. Five starter proteins were studied. Three (egg albumin, casein/soy/lactalbumin, and lactalbumin) were hydrolysed by papain, a second lactalbumin starter protein, and a meat/soy/lactalbumin blend were hydrolysed by a porcine pancreatic enzyme system. Irrespective of starter protein composition or hydrolysis method used, four amino acid residues (threonine, glutamic acid, phenylalanine, and histidine) were absorbed significantly faster from all hydrolysates compared with absorption from their equivalent free amino acid mixtures. In contrast, both starter protein composition and hydrolysis method influenced absorption characteristics of up to nine other amino acid residues. PMID:4029718

  17. A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption

    PubMed Central

    Widjaja-Adhi, M. Airanthi K.; Lobo, Glenn P.; Golczak, Marcin; Von Lintig, Johannes

    2015-01-01

    Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency. Surprisingly, responses to dietary supplementation with these compounds are quite variable between individuals. Genome-wide studies have associated common genetic polymorphisms in the BCO1 gene with this variability. The BCO1 gene encodes an enzyme that is expressed in the intestine and converts provitamin A carotenoids to vitamin A-aldehyde. However, it is not clear how this enzyme can impact the bioavailability and metabolism of other carotenoids such as xanthophyll. We here provide evidence that BCO1 is a key component of a regulatory network that controls the absorption of carotenoids and fat-soluble vitamins. In this process, conversion of β-carotene to vitamin A by BCO1 induces via retinoid signaling the expression of the intestinal homeobox transcription factor ISX. Subsequently, ISX binds to conserved DNA-binding motifs upstream of the BCO1 and SCARB1 genes. SCARB1 encodes a membrane protein that facilitates absorption of fat-soluble vitamins and carotenoids. In keeping with its role as a transcriptional repressor, SCARB1 protein levels are significantly increased in the intestine of ISX-deficient mice. This increase results in augmented absorption and tissue accumulation of xanthophyll carotenoids and tocopherols. Our study shows that fat-soluble vitamin and carotenoid absorption is controlled by a BCO1-dependent negative feedback regulation. Thus, our findings provide a molecular framework for the controversial relationship between genetics and fat-soluble vitamin status in the human population. PMID:25701869

  18. Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract

    PubMed Central

    Shan, Jinjun; Zou, Jiashuang; Xie, Tong; Kang, An; Zhou, Wei; Deng, Haishan; Mao, Yancao; Di, Liuqing; Wang, Shouchuan

    2015-01-01

    Background: Platycodi radix, the dried root of Platycodon grandiflorum A. DC, has been widely used as food and herb medicine for treating cough, cold and other respiratory ailments, and platycodin D (PD) is one of the most important compounds in Platycodi Radix. Objective: The purpose of this study was to compare the pharmacokinetic characteristics, intestinal absorption and microbial metabolism of PD in monomer with that in Platycodi radix extract (PRE). Materials and Methods: In the pharmacokinetic study, the concentrations of PD in rat plasma were determined by ultra-performance liquid chromatography-tandem mass spectrometry and the main pharmacokinetic parameters were calculated by data analysis software (DAS). Besides, in vitro Caco-2 cells and fecal lysate were performed to investigate the intestinal absorption and metabolism, respectively. Results: The results from pharmacokinetics showed that the area under the curve, the peak concentration the time to reach peak concentration and mean residence time of PD in PRE were enhanced significantly compared with that in single PD. Caco-2 cells transport study indicated that the absorption of PD both in monomer and in PRE were poor owning that the permeability of PD were <1/106 cm/s. The hydrolysis degree of PD in PRE was significantly lower than that in monomer PD in fecal lysate, which might be illustrated by the other ingredients in PRE influenced the hydrolysis of PD via gut microbiota. Conclusion: These findings indicated that the difference of microbial metabolism, not apparent absorption in intestine for PD between in monomer and in PRE contributed to their pharmacokinetic difference. PMID:26600720

  19. Characterization of the oral absorption of several aminopenicillins: determination of intrinsic membrane absorption parameters in the rat intestine in situ

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Amidon, G. L.

    1992-01-01

    The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane parameters were determined using a modified boundary layer model (fitted value +/- S.E.): Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 1.14 +/- 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition.

  20. [Intestinal absorption and urinary excretion of triethylenetetramine for Wilson's disease in rat].

    PubMed

    Kobayashi, M; Sugawara, M; Saitoh, H; Iseki, K; Miyazaki, K

    1990-10-01

    Triethylenetetramine.2.HCl (trientine, TE) is an orphan drug for the treatment of Wilson's disease. There has been no reports regarding the absorption, distribution, metabolism, and excretion in the body. In the current study, the absorption and excretion of TE in rats were examined. The observed mean percentage amount of TE absorbed at the jejunum and ileum with the loop method for 1 h was 42.0% and 22.5%, respectively. Tight junction blocking agent inhibited the absorption of TE from the jejunum loop with 27%, but the absorption of TE from the ileum loop was not affected by this blocking agent. Therefore, the main absorption route for TE might be permeation across the plasma membrane of intestinal epithelial cells. TE and amikacin, a polycationic compound like TE, bound to the brush border membrane (BBM) of rat small intestine in the absence of inorganic ions such as Na+, K+, Ca2+, Mg2+ and Cu2+. But the binding of TE to BBM was inhibited markedly under the physiological concentration of these ions. The bioavailability of TE was below 10% and the plasma levels of TE in non-fasted rats were significantly lower than that observed in fasted rats. The urinary excretion of unchanged TE during 24 h was only 3.5% of the orally administered dose. However, the urinary excretion of total TE including metabolites, though they have not been identified, was 35.7%. These results suggest that low bioavailability of TE might be due to the rapid metabolism in the body after absorption from the gastrointestinal tract.

  1. Detection of Glucose with Atomic Absorption Spectroscopy by Using Oligonucleotide Functionalized Gold Nanoparticle.

    PubMed

    Zhang, Hong; Yan, Honglian; Ling, Liansheng

    2016-06-01

    A novel method for the detection of glucose was established with atomic absorption spectroscopy by using the label of gold nanoparticle (AuNP). Silver-coated glass assembled with oligonucleotide 5'-SH-T12-AGA CAA GAG AGG-3' (Oligo 1) was acted as separation probe, oligonucleotide 5'-CAA CAG AGA ACG-T12-SH-3' modified gold nanoparticle (AuNP-Oligo 2) was acted as signal-reporting probe. Oligonucleotide 5'-CGT TCT CTG TTG CCT CTC TTG TCT-3' (Oligo 3) could hybridize with Oligo 1 on the surface of silver-coated glass and AuNP-Oligo 2, and free AuNP-Oligo 2 could be removed by rinsing with buffer. Hence the concentration of Oligo 3 was transformed into the concentration of gold element. In addition, Oligo 3 could be cleaved into DNA fragments by glucose, glucose oxidase and Fe(2+)-EDTA through Fenton reaction. Thereby the concentration of glucose could be transformed to the absorbance of gold element. Under the optimum conditions, the integrated absorbance decreased proportionally to the concentration of glucose over the range from 50.0 μM to 1.0 mM with a detection limit of 40.0 μM. Moreover, satisfactory result was obtained when the assay was used to determinate glucose in human serum. PMID:27427698

  2. Detection of Glucose with Atomic Absorption Spectroscopy by Using Oligonucleotide Functionalized Gold Nanoparticle.

    PubMed

    Zhang, Hong; Yan, Honglian; Ling, Liansheng

    2016-06-01

    A novel method for the detection of glucose was established with atomic absorption spectroscopy by using the label of gold nanoparticle (AuNP). Silver-coated glass assembled with oligonucleotide 5'-SH-T12-AGA CAA GAG AGG-3' (Oligo 1) was acted as separation probe, oligonucleotide 5'-CAA CAG AGA ACG-T12-SH-3' modified gold nanoparticle (AuNP-Oligo 2) was acted as signal-reporting probe. Oligonucleotide 5'-CGT TCT CTG TTG CCT CTC TTG TCT-3' (Oligo 3) could hybridize with Oligo 1 on the surface of silver-coated glass and AuNP-Oligo 2, and free AuNP-Oligo 2 could be removed by rinsing with buffer. Hence the concentration of Oligo 3 was transformed into the concentration of gold element. In addition, Oligo 3 could be cleaved into DNA fragments by glucose, glucose oxidase and Fe(2+)-EDTA through Fenton reaction. Thereby the concentration of glucose could be transformed to the absorbance of gold element. Under the optimum conditions, the integrated absorbance decreased proportionally to the concentration of glucose over the range from 50.0 μM to 1.0 mM with a detection limit of 40.0 μM. Moreover, satisfactory result was obtained when the assay was used to determinate glucose in human serum.

  3. Intestinal absorption of forsythoside A in different compositions of Shuang-Huang-Lian.

    PubMed

    Zhou, Wei; Di, Liu-qing; Shan, Jin-jun; Bi, Xiao-lin; Chen, Le-tian; Wang, Ling-chong

    2011-04-01

    Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is commonly used to treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. Forsythoside A is one of the main active ingredients in Forsythiae fructus, a key herb in SHL. In the present study, effects of different compositions in SHL on the intestinal absorption of forsythoside A were investigated. The observations from in situ intestinal circulation model showed that A/%(h(-1)) of forsythoside A in FF+LSF, FF+SR and SHL were all reduced greatly compared with that in FF. However, in pharmacokinetics study, C(max) and AUC(0→1440) of forsythoside A all increased and T(1/2) prolonged in SHL, FF+LJF and FF+SR compared with FF. The results indicated that the different compositions of SHL decreased absorption but increased bioavailability of forsythoside A, which may be related to its metabolism inhibited in intestine or liver.

  4. Intestinal synthesis and absorption of vitamin B-12 in channel catfish

    SciTech Connect

    Limsuwan, T.; Lovell, R.T.

    1981-12-01

    A feeding experiment conducted in a controlled environment and using a vitamin B12-deficient, but otherwise nutritionally complete, purified diet revealed that intestinal microorganisms in channel catfish synthesized approximately 1.4 ng of vitamin B12 per gram of bodyweight per day. Removal of cobalt from the diet or supplementation with an antibiotic (succinylsulfathiazole) significantly reduced the rate of intestinal synthesis and liver stores of vitamin B12. Radiolabeled vitamin B12 in the blood, liver, kidneys, and spleen of fish fed 60Co in the diet indicated that the intestinally synthesized vitamin was absorbed by the fish. The primary route of absorption was directly from the digestive tract into the blood because coprophagy was prevented in the rearing aquariums and the amount of vitamin B12 dissolved in the aquarium water was too low for gill absorption. Dietary supplementation of vitamin B12 was not necessary for normal growth and erythrocyte formation in channel catfish in a 24-week feeding period. A longer period, however, may have caused a vitamin deficiency since liver-stored vitamin B 12 decreased between the 2nd and 24th weeks.

  5. Small Intestinal Bacterial Overgrowth Diagnosed by Glucose Hydrogen Breath Test in Post-cholecystectomy Patients

    PubMed Central

    Sung, Hea Jung; Paik, Chang-Nyol; Chung, Woo Chul; Lee, Kang-Moon; Yang, Jin-Mo; Choi, Myung-Gyu

    2015-01-01

    Background/Aims Patients undergoing cholecystectomy may have small intestinal bacterial overgrowth (SIBO). We investigated the prevalence and characteristics of SIBO in patients with intestinal symptoms following cholecystectomy. Methods Sixty-two patients following cholecystectomy, 145 with functional gastrointestinal diseases (FGIDs), and 30 healthy controls undergoing hydrogen (H2)-methane (CH4) glucose breath test (GBT) were included in the study. Before performing GBT, all patients were interrogated using bowel symptom questionnaire. The positivity to GBT indicating the presence of SIBO, gas types and bowel symptoms were surveyed. Results Post-cholecystectomy patients more often had SIBO as evidenced by a positive (+) GBT than those with FGID and controls (29/62, 46.8% vs 38/145, 26.2% vs 4/30, 13.3%, respectively; P = 0.010). In the gas types, the GBT (H2) + post-cholecystectomy patients was significantly higher than those in FGIDs patients (P = 0.017). Especially, positivity to fasting GBT (H2) among the GBT (H2)+ post-cholecystectomy patients was high, as diagnosed by elevated fasting H2 level. The GBT+ group had higher symptom scores of significance or tendency in abdominal discomfort, bloating, chest discomfort, early satiety, nausea, and tenesmus than those of the GBT negative group. The status of cholecystectomy was the only significant independent factor for predicting SIBO. Conclusions The SIBO with high levels of baseline H2 might be the important etiologic factor of upper GI symptoms for post-cholecystectomy patients. PMID:26351251

  6. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei

    PubMed Central

    Yan, Xiang Mei; Kim, Chung-Hyo; Lee, Chul Kyu; Shin, Jang Sik; Cho, Il Hwan

    2010-01-01

    To investigate the intestinal absorption of a fibrinolytic and proteolytic lumbrokinase extracted from Eisenia andrei, we used rat everted gut sacs and an in situ closed-loop recirculation method. We extracted lumbrokinase from Eisenia andrei, and then raised polyclonal antibody against lumbrokinase. Fibrinolytic activity and proteolytic activity in the serosal side of rat everted gut sacs incubated with lumbrokinase showed dose- and time-dependent patterns. Immunological results obtained by western blotting serosal side solution using rat everted gut sacs method showed that lumbrokinase proteins between 33.6 and 54.7 kDa are absorbed mostly by the intestinal epithelium. Furthermore, MALDI-TOF mass spectrometric analysis of plasma fractions obtained by in situ recirculation method confirmed that lumbrokinase F1 is absorbed into blood. These results support the notion that lumbrokinase can be absorbed from mucosal lumen into blood by oral administration. PMID:20473377

  7. Effect of dietary calcium: Phosphorus ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats.

    PubMed

    Koshihara, Moyuru; Masuyama, Ritsuko; Uehara, Mariko; Suzuki, Kazuharu

    2004-01-01

    We investigated the effect of dietary calcium:phosphorus (Ca:P) ratio on bone mineralization and intestinal Ca absorption in ovariectomized (OVX) rat models of osteoporosis and sham-operated rats. Thirty 12-wk-old female Wistar rats were divided into three groups of OVX rats and three groups of sham rats. Thirty days after the adaptation period, OVX rats and sham rats were fed a diet formulated Ca:P, 1:0.5, 1:1 or 1:2 (each diet containing 0.5% Ca), respectively for 42 d. In both sham and OVX rats, serum osteocalcin, a marker of bone turnover, was increased by decreasing Ca:P ratio (1:2). In contrast, rats fed the Ca:P = 1:0.5 diet (dietary P restriction) suppressed the increased serum parathyroid hormone, osteocalcin and urinary deoxypyridinoline, and increased Ca absorption in both sham and OVX rats compared to the Ca:P = 1:1 and 1:2 diets. Especially, in OVX rats, the decreased bone mineral density of the fifth lumbar was also suppressed when rats were fed the Ca:P = 1:0.5 diet. These results indicated that the elevation of dietary Ca:P ratio may inhibit bone loss and increase intestinal Ca absorption in OVX rats.

  8. Microscopic modeling of País grape seed extract absorption in the small intestine.

    PubMed

    Morales, Cristian; Roeckel, Marlene; Fernández, Katherina

    2014-02-01

    The concentration profiles and the absorbed fraction (F) of the País grape seed extract in the human small intestine were obtained using a microscopic model simulation that accounts for the extracts' dissolution and absorption. To apply this model, the physical and chemical parameters of the grape seed extract solubility (C s), density (ρ), global mass transfer coefficient between the intestinal and blood content (k) (effective permeability), and diffusion coefficient (D) were experimentally evaluated. The diffusion coefficient (D = 3.45 × 10(-6) ± 5 × 10(-8) cm(2)/s) was approximately on the same order of magnitude as the coefficients of the relevant constituents. These results were chemically validated to discover that only the compounds with low molecular weights diffused across the membrane (mainly the (+)-catechin and (-)-epicatechin compounds). The model demonstrated that for the País grape seed extract, the dissolution process would proceed at a faster rate than the convective process. In addition, the absorbed fraction was elevated (F = 85.3%). The global mass transfer coefficient (k = 1.53 × 10(-4) ± 5 × 10(-6) cm/s) was a critical parameter in the absorption process, and minor changes drastically modified the prediction of the extract absorption. The simulation and experimental results show that the grape seed extract possesses the qualities of a potential phytodrug.

  9. A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine

    SciTech Connect

    Bergstedt, S.E.; Hayashi, H.; Kritchevsky, D.; Tso, P. )

    1990-09-01

    Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri(9,10 (n)-3H)oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl (1,3-14C)tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.

  10. Low zinc status and absorption exist in infants with jejunostomies or ileostomies which persists after intestinal repair

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer s...

  11. Preparation of tripterine nanostructured lipid carriers and their absorption in rat intestine.

    PubMed

    Zhou, Lei; Chen, Yan; Zhang, Zhenhai; He, Junjie; Du, Meng; Wu, Qingqing

    2012-04-01

    The purpose of this study was to develop an optimized nanostructured lipid carrier formulation (NLC) for tripterine, and to estimate the potential of NLCs as oral delivery system. Tripterine-loaded NLCs were prepared by the solvent evaporation method. The average drug entrapment efficiency, particle size and zeta potential of the optimized tripterine-loaded NLCs were 78.64 +/- 0.37%, 109.6 +/- 5.8 nm and -29.8 +/- 1.3 mV, respectively. The tripterine-loaded NLCs showed spherical morphology with smooth surface under the transmission electron microscope (TEM). The crystallization of drug in NLC was investigated by differential scanning calorimetry (DSC). The drug was in an amorphous state in the NLC matrix. According to the in vitro release study, the tripterine-loaded NLCs showed a delayed release profile of tripterine. The rat intestinal perfusion model was used to study the absorption of tripterine solution and tripterine-loaded NLCs. The Peff* (effective permeability) of tripterine-loaded NLCs in the duodenum, jejunum, ileum and colon was approximately 2.1, 2.7, 1.1, 1.2-fold higher than that of tripterine solution, respectively. The 10% ABS (percent absorption of 10 cm of intestine) of tripterine-loaded NLCs in the duodenum, jejunum, ileum and colon was approximately 2.2, 2.3, 1.2, 1.3-fold higher than that of tripterine solution, respectively. The intestinal toxicity of tripterine formulated in the NLCs was investigated and compared with the tripterine solution by the MTT assay with Caco-2 cell models. According to the result, the tripterine-loaded NLCs could greatly decrease the cytotoxicity of the drug. In conclusion, the NLC formulation remarkably improved the absorption of tripterine and showed a better biocompatibility.

  12. Increased intracellular calcium level and impaired nutrient absorption are important pathogenicity traits in the chicken intestinal epithelium during Campylobacter jejuni colonization.

    PubMed

    Awad, Wageha A; Smorodchenko, Alina; Hess, Claudia; Aschenbach, Jörg R; Molnár, Andor; Dublecz, Károly; Khayal, Basel; Pohl, Elena E; Hess, Michael

    2015-08-01

    Although a high number of chickens carry Campylobacter jejuni, the mechanistic action of colonization in the intestine is still poorly understood. The current study was therefore designed to investigate the effects of C. jejuni on glucose uptake, amino acids availability in digesta, and intracellular calcium [Ca(2+)]i signaling in the intestines of broiler chickens. For this, we compared: control birds (n = 60) and C. jejuni-infected birds (n = 60; infected orally with 1 × 10(8) CFU of C. jejuni NCTC 12744 at 14 days of age). Our results showed that glucose uptake was reduced due to C. jejuni infection in isolated jejunal, but not in cecal mucosa at 14 days postinfection (dpi). The decrease in intestinal glucose absorption coincided with a decrease in body weight gain during the 2-week post-infectious period. A reduction in the amount of the amino acids (serine, proline, valine, leucine, phenylalanine, arginine, histidine, and lysine) in ileal digesta of the infected birds at 2 and/or 7 dpi was found, indicating that Campylobacter utilizes amino acids as a carbon source for their multiplication. Applying the cell-permeable Ca(2+) indicator Fluo-4 and two-photon microscopy, we revealed that [Ca(2+)]i was increased in the jejunal and cecal mucosa of infected birds. The muscarinic agonist carbachol induced an increase in [Ca(2+)]i in jejunum and cecum mucosa of control chickens, a response absent in the mucosa of infected chickens, demonstrating that the modulation of [Ca(2+)]i by Campylobacter might be involved in facilitating the necessary cytoskeletal rearrangements that occur during the bacterial invasion of epithelial cells. In conclusion, this study demonstrates the multifaceted interactions of C. jejuni with the gastrointestinal mucosa of broiler chickens. For the first time, it could be shown that a Campylobacter infection could interfere with intracellular Ca(2+) signaling and nutrient absorption in the small intestine with consequences on

  13. [The role of gastro-intestinal tract in the calcium absorption].

    PubMed

    Kuwabara, Akiko; Tanaka, Kiyoshi

    2015-11-01

    Calcium is associated with various functions of clinical importance. Its unique distribution;low intracellular and high extracellular concentration, is crucial for the neuro-muscular function. Calcium is also indispensable for the vascular contraction and blood coagulation. Thus, circulating calcium concentration must be strictly maintained within a narrow range, for which parathyroid hormone(PTH), vitamin D, and calcitonin contribute. Food-derived protein-bound calcium must be first released in the acidic condition. Thus, gastric acid is essential for the effective calcium absorption. Intestinal calcium absorption occurs via both active transport and passive transport. For the former, such molecules as transient receptor potential vanilloid type 6(TRPV6), calbindin 9k, and Ca²⁺-ATPase contribute. In the adult, calcium absorption rate is approximately 30% under the ordinary condition. Lower calcium intake is associated with increased calcium absorption and decreased urinary excretion. In the Dietary Reference Intakes for Japanese, calcium requirement is determined based on factorial method. Recommended Dietary Allowance(RDA)for calcium ranges from 600-800 mg/day for adult. However, the average calcium intake is far lower than Estimated Average Requirement(EAR). Thus, an effort to increase the calcium intake, rather than considering the detailed calcium absorption rate, is most essential in Japan.

  14. [The role of gastro-intestinal tract in the calcium absorption].

    PubMed

    Kuwabara, Akiko; Tanaka, Kiyoshi

    2015-11-01

    Calcium is associated with various functions of clinical importance. Its unique distribution;low intracellular and high extracellular concentration, is crucial for the neuro-muscular function. Calcium is also indispensable for the vascular contraction and blood coagulation. Thus, circulating calcium concentration must be strictly maintained within a narrow range, for which parathyroid hormone(PTH), vitamin D, and calcitonin contribute. Food-derived protein-bound calcium must be first released in the acidic condition. Thus, gastric acid is essential for the effective calcium absorption. Intestinal calcium absorption occurs via both active transport and passive transport. For the former, such molecules as transient receptor potential vanilloid type 6(TRPV6), calbindin 9k, and Ca²⁺-ATPase contribute. In the adult, calcium absorption rate is approximately 30% under the ordinary condition. Lower calcium intake is associated with increased calcium absorption and decreased urinary excretion. In the Dietary Reference Intakes for Japanese, calcium requirement is determined based on factorial method. Recommended Dietary Allowance(RDA)for calcium ranges from 600-800 mg/day for adult. However, the average calcium intake is far lower than Estimated Average Requirement(EAR). Thus, an effort to increase the calcium intake, rather than considering the detailed calcium absorption rate, is most essential in Japan. PMID:26503863

  15. Intestinal absorption, blood transport and hepatic and muscle metabolism of fatty acids in preruminant and ruminant animals.

    PubMed

    Hocquette, J F; Bauchart, D

    1999-01-01

    Current research on lipid metabolism in ruminants aims to improve the growth and health of the animals and the muscle characteristics associated with meat quality. This review, therefore, focuses on fatty acid (FA) metabolism from absorption to partitioning between tissues and metabolic pathways. In young calves, which were given high-fat milk diets, lipid absorption is delayed because the coagulation of milk caseins results in the retention of dietary fat as an insoluble clot in the abomasum. After weaning, the calves were fed forage- and cereal-based diets containing low levels of long-chain fatty acids (LCFA) but leading to high levels of volatile fatty acid (VFA) production by the rumen microflora. Such differences in dietary FA affect: i) the lipid transport system via the production of lipoproteins by the intestine and the liver, and (ii) the subsequent metabolism of lipids and FA by tissues. In preruminant calves, high-fat feed stimulates the secretion of triacylglycerols (TG)-rich lipoproteins (chylomicrons, very-low density lipoproteins (VLDL)). Diets rich in polyunsaturated FA (PUFA) stimulate the production of chylomicrons by the intestine (at peak lipid absorption) and of high density lipoproteins by the liver, leading to high blood concentrations of cholesterol. High levels of non-esterified FA (NEFA) uptake by the liver in high-yielding dairy cows in early lactation leads to TG infiltration of the hepatocytes (fatty liver). This is due to the low chronic capacity of the liver to synthesise and secrete VLDL particles. This abnormality in hepatic FA metabolism involves defects in apolipoprotein B synthesis and low availability of apolipoproteins and lipids for VLDL packaging. Fatty liver in calves is also caused by milk containing either soybean oil (rich in n-6 PUFA), or coconut oil (rich in C12:0 and C14:0). The ability of muscle tissue to use FA as an energy source depends on its mitochondrial content and, hence, on many physiological factors. The

  16. Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across the Rat Small Intestinal Membrane.

    PubMed

    Khafagy, El-Sayed; Iwamae, Ruisha; Kamei, Noriyasu; Takeda-Morishita, Mariko

    2015-11-01

    We have reported that the cell-penetrating peptide (CPP) penetratin acts as a potential absorption enhancer in oral insulin delivery systems and that this action occurs through noncovalent intermolecular interactions. However, the region-dependent role of CPPs in intestinal insulin absorption has not been clarified. To identify the intestinal region where CPPs have the most effect in increasing insulin absorption, the region-dependent action of penetratin was investigated using in situ closed intestinal loops in rats. The order of the insulin area under the insulin concentration-time curve (AUC) increase effect by L-penetratin was ileum > jejunum > duodenum > colon. By contrast, the AUC order after coadministration of insulin with D-penetratin was colon > duodenum ≥ jejunum and ileum. We also compared the effects of the L- and D-forms of penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs used in this study, L- and D-PenetraMax produced the largest insulin AUCs. An absorption study using ilea pretreated with CPPs showed that PenetraMax had no irreversible effect on the intestinal epithelial membrane. The degradation of insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid. The half-life (t 1/2) of insulin increased from 14.5 to 23.7 and 184.7 min in the presence of L- and D-PenetraMax, respectively. These enzymatic degradation-resistant effects might contribute partly to the increased ileal absorption of insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the ability of the L- and D-forms of penetratin to increase intestinal insulin absorption was maximal in the ileum and the colon, respectively, and that D-PenetraMax is a powerful but transient enhancer of oral insulin absorption.

  17. A review of laboratory tests of intestinal absorption in the tropics.

    PubMed

    Falaiye, J M

    1976-09-01

    The intestinal absorptive capacity for xylose and folic acid has frequently been found to be defective in apparently normal asymptomatic residents of the tropics. This suggests the presence among the natives of the tropics of appreciable, yet asymptomatic jejunal functional incompetence which is not seen in the temperate countries. Further, structural abnormalities in the villi which are non-specific occur in varying degrees of severity in the tropics both in health and in disease. These tropical peculiarities raise obvious doubts as to the diagnostic usefulness of these laboratory tests in the evaluation of disorders of absorption in tropical practice. In this review, experiences from the Lagos University Teaching Hospital had shown that the faecal fat analysis for the detection of steatorrhoea is the most dependable single diagnostic and in studies of overt malabsorption in Niageria.

  18. Human chorionic gonadotropin promotes expression of protein absorption factors in the intestine of goldfish (Carassius auratus).

    PubMed

    Zhou, Y; Hao, G; Zhong, H; Wu, Q; Lu, S Q; Zhao, Q; Liu, Z

    2015-07-27

    Protein use is crucial for the ovulation and spawning of fish. Currently, limited information is available regarding the expression of protein absorption factors during the breeding seasons of teleosts and thus how various proteins involved in this process is not well-understood. The expression of CDX2, CREB, gluatamate dehydrogenase, LAT2, aminopeptidase N, PepT1, and SP1 were significantly elevated from the non-breeding season to the breeding season in female goldfish, and all proteins except PepT1 and SP1 were elevated in male goldfish. Injection of human chorionic gonadotropin upregulated the expression of all proteins except for aminopeptidase N in female goldfish and SP1 in male goldfish, suggesting a luteinizing hormone-inductive effect on protein absorption factors. Protein use in the intestine is increased during the breeding seasons as a result of increased luteinizing hormone.

  19. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs

    PubMed Central

    Boutjdir, Mohamed; Rudel, Lawrence L.; Hussain, M. Mahmood

    2014-01-01

    Intestinal cholesterol absorption involves the chylomicron and HDL pathways and is dependent on microsomal triglyceride transfer protein (MTP) and ABCA1, respectively. Chylomicrons transport free and esterified cholesterol, whereas HDLs transport free cholesterol. ACAT2 esterifies cholesterol for secretion with chylomicrons. We hypothesized that free cholesterol accumulated during ACAT2 deficiency may be secreted with HDLs when chylomicron assembly is blocked. To test this, we studied cholesterol absorption in mice deficient in intestinal MTP, global ACAT2, and both intestinal MTP and global ACAT2. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their transport with chylomicrons. In contrast, global ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption with chylomicrons and increased cellular free cholesterol. Their combined deficiency reduced cholesterol secretion with both chylomicrons and HDLs. Thus, contrary to our hypothesis, free cholesterol accumulated in the absence of MTP and ACAT2 is unavailable for secretion with HDLs. Global ACAT2 deficiency causes mild hypertriglyceridemia and reduces hepatosteatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in global ACAT2-deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid hepatosteatosis in cholesterol-fed animals. Therefore, ACAT2 inhibition might avert hepatosteatosis associated with high cholesterol diets by increasing hepatic MTP expression and lipoprotein production. PMID:25030663

  20. Unstirred layer and kinetics of electrogenic glucose absorption in the human jejunum in situ

    PubMed Central

    Read, N. W.; Barber, D. C.; Levin, R. J.; Holdsworth, C. D.

    1977-01-01

    Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 ± 24 μm: mean ± SEM) was significantly thicker than in 10 patients with active coeliac disease (442 ± 23 μm) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 ± 49 μm). There were similar differences in the values of `Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 ± 6 mM) active coeliac patients (11 ± 1 mM) and treated coeliac patients (31 ± 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6·8 ± 0·7 mV) was lower than in controls (7·6 ± 0·6 mV) but not significantly so, while the PDmax in the treated coeliac group (10·6 ± 0·9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (`Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health. PMID:590846

  1. Iris as a reflector for differential absorption low-coherence interferometry to measure glucose level in the anterior chamber

    NASA Astrophysics Data System (ADS)

    Zhou, Yong; Zeng, Nan; Ji, Yanhong; Li, Yao; Dai, Xiangsong; Li, Peng; Duan, Lian; Ma, Hui; He, Yonghong

    2011-01-01

    We present a method of glucose concentration detection in the anterior chamber with a differential absorption optical low-coherent interferometry (LCI) technique. Back-reflected light from the iris, passing through the anterior chamber twice, was selectively obtained with the LCI technique. Two light sources, one centered within (1625 nm) and the other centered outside (1310 nm) of a glucose absorption band were used for differential absorption measurement. In the eye model and pig eye experiments, we obtained a resolution glucose level of 26.8 mg/dL and 69.6 mg/dL, respectively. This method has a potential application for noninvasive detection of glucose concentration in aqueous humor, which is related to the glucose concentration in blood.

  2. In vivo measurement of the absorption of strontium in the rumen and small intestine of sheep as an index of calcium absorption capacity.

    PubMed

    Hyde, Michelle L; Fraser, David R

    2014-09-14

    In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon simultaneous administration of an oral dose of stable Sr and radioactive calcium (r 0·98). The Ca absorption capacity of the rumen and small intestine was determined separately by either directing the solution into the rumen or by diverting it into the post-ruminal tract by vasopressin-induced closure of the ruminoreticular groove. The animals were treated with 1α-hydroxyvitamin D3 administered via subcutaneously implanted mini-osmotic pumps. The effect of elevated plasma 1,25-dihydroxycholecalciferol concentrations on the Ca absorption capacity of the alimentary tract was then determined. An increased rate of Sr absorption was observed in both the rumen and small intestine of sheep after treatment, although it is unclear whether the rumen possesses the same vitamin D-dependent Ca absorption pathway as the small intestine.

  3. Effect of dietary phosphorus on intestinal phosphorus absorption in growing Holstein steers.

    PubMed

    Feng, X; Ronk, E; Hanigan, M D; Knowlton, K F; Schramm, H; McCann, M

    2015-05-01

    The effect of dietary P intake on intestinal P absorption was evaluated in growing Holstein steers. Diets varying in P content (0.15, 0.27, 0.36, and 0.45%, DM basis) were fed to 8 steers (174±10kg of BW) fitted with permanent duodenal and ileal cannulas in a replicated 4×4 Latin square with 14-d periods. Ytterbium-labeled corn silage and cobalt-EDTA were used as particulate and liquid phase markers, respectively, to measure digesta flow. Duodenal and ileal samples and spot urine samples were collected every 9 h from d 11 to 14. Total fecal collection was conducted on d 11 to 14 with fecal bags. Blood samples were collected from the coccygeal vessel on d 14. Feed, digesta, and fecal samples were analyzed for total P and inorganic P. Data were analyzed using PROC GLIMMIX in SAS with a model including treatment, square, period, and interaction of treatment and square. Preplanned contrasts were used to evaluate linear and quadratic treatment effects. Results were reported as least squares means. Dry matter intake (mean=4.90kg/d, 2.8% of BW) and apparent DM digestibility (mean=78.1%) were unaffected by treatment. Duodenal and ileal flow of total P increased linearly with increasing P intake (13.4, 18.5, 23.0, and 27.4g/d; 6.80, 7.87, 8.42, and 10.4g/d). Increasing P intake increased the quantity of P absorbed from the small intestine linearly (6.96, 11.1, 14.6, and 17.2g/d), but absorption efficiency was unchanged (mean=59.6%). Phosphorus was absorbed on a net basis from the large intestine, but this was not affected by treatment and was a small proportion of total P absorption. Blood inorganic P increased linearly with increased dietary P (4.36, 6.31, 7.68, and 8.5mg/dL) and salivary P secretion was unchanged (mean=5.79g/d), suggesting that rumen function was prioritized during short-term P deficiency. These data showing an absence of change in absorption efficiency and salivary P secretion in the face of short-term P deficiency may be used to improve published

  4. Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical preparation.

    PubMed

    Werner, E; Hansen, Ch; Roth, P; Kaltwasser, J P

    1999-01-01

    Only few data are available on intestinal calcium absorption from foodstuffs and composite meals in humans. The aim of the study was to compare intraindividually the calcium absorption from milk and from a breakfast with that from a pharmaceutical calcium preparation of equal calcium content. In 8 healthy volunteers between 44 and 58 years of age, the intestinal calcium absorption was measured in randomized order applying the double isotope technique from: (1) 500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg 42Ca in a sterile isotonic solution were injected intravenously. The mean values of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and 28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The data show that less calcium is absorbed from foodstuffs as compared to a preparation of optimal bioavailability. But in this study only the difference between absorption from the milk and from the meal was statistically significant. Therefore, it is possible to obtain a sufficient calcium supply of the human body also by properly selected foodstuffs.

  5. Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells

    PubMed Central

    Botchlett, Rachel; Li, Honggui; Guo, Xin; Qi, Ting; Zhao, JiaJia; Zheng, Juan; Woo, Shih-Lung; Pei, Ya; Liu, Mengyang; Hu, Xiang; Chen, Guang; Guo, Ting; Yang, Sijun; Li, Qifu; Xiao, Xiaoqiu; Huo, Yuqing; Wu, Chaodong

    2016-01-01

    The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 μmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients. PMID:27387960

  6. Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells.

    PubMed

    Botchlett, Rachel; Li, Honggui; Guo, Xin; Qi, Ting; Zhao, JiaJia; Zheng, Juan; Woo, Shih-Lung; Pei, Ya; Liu, Mengyang; Hu, Xiang; Chen, Guang; Guo, Ting; Yang, Sijun; Li, Qifu; Xiao, Xiaoqiu; Huo, Yuqing; Wu, Chaodong

    2016-07-08

    The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 μmol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients.

  7. Human Milk Oligosaccharides in Premature Infants: Absorption, Excretion and Influence on the Intestinal Microbiota

    PubMed Central

    Underwood, Mark A.; Gaerlan, Stephanie; De Leoz, M. Lorna A.; Dimapasoc, Lauren; Kalanetra, Karen M.; Lemay, Danielle G.; German, J. Bruce; Mills, David A.; Lebrilla, Carlito B.

    2015-01-01

    Background Human milk oligosaccharides (HMOs) shape the intestinal microbiota in term infants. In premature infants, alterations in the intestinal microbiota (dysbiosis) are associated with risk of necrotizing enterocolitis and sepsis and the influence of HMOs on the microbiota is unclear. Methods Milk, urine, and stool specimens from 14 mother-premature infant dyads were investigated by mass spectrometry for HMO composition. The stools were analyzed by next-generation sequencing (NGS) to complement a previous analysis. Results Percentages of fucosylated and sialylated HMOs were highly variable between individuals but similar in urine, feces and milk within dyads. Differences in urine and fecal HMO composition suggest variability in absorption. Secretor status of the mother correlated with the urine and fecal content of specific HMO structures. Trends toward higher levels of Proteobacteria and lower levels of Firmicutes, were noted in premature infants of non-secretor mothers. Specific HMO structures in the milk, urine and feces were associated with alterations in fecal Proteobacteria and Firmicutes. Conclusion HMOs may influence the intestinal microbiota in premature infants. Specific HMOs, for example those associated with secretor mothers, may have a protective effect by decreasing pathogens associated with sepsis and necrotizing enterocolitis while other HMOs may increase dysbiosis in this population. PMID:26322410

  8. Intestinal calcium absorption and response of calcium regulating hormones in the stroke-prone spontaneously hypertensive rat as a model of osteoporosis.

    PubMed

    Fukuda, S; Tsuchikura, S; Iida, H; Ikeda, K; Nara, Y; Yamori, Y

    1995-12-01

    1. Because of low levels of serum calcium (Ca) in stroke-prone spontaneously hypertensive rats (SHRSP), intestinal Ca absorption and urinary Ca excretion were examined. 2. SHRSP were observed to have lower intestinal Ca absorption and higher urinary Ca excretion, but with a latent function of intestinal Ca absorption able to respond with calcium regulating hormones to Ca loading in the aged, especially to a new Ca agent as examined in this study. PMID:9072373

  9. Regional intestinal absorption of FITC-dextran 4,400 with nanoparticles based on beta-sitosterol beta-D-glucoside in rats.

    PubMed

    Nakamura, Koji; Takayama, Kozo; Nagai, Tsuneji; Maitani, Yoshie

    2003-02-01

    Nanoparticles (NP) are potential carriers for drug delivery to the targeted intestine. NP based on beta-sitosterol beta-D-glucoside (Sit-G) enhanced the colon-specific absorption of FITC-dextran 4,400 (FD-4), because the concentration-dependent increase of bioavailability appeared in only the colon. In a permeation study, the absorption enhancement in the colon was suppressed in the following conditions: (1) the addition of Sit-G NP to serosa; (2) a permeation study at 4 degrees C; (3) the addition of endocytosis inhibitor, cytochalasin B. NP based on sitosterol, the aglycon of Sit-G, did not increase the FD-4 colonic permeation. The addition of Sit-G NP to the mucosal side induced a decrease of transepithelial resistance (TEER), but this phenomenon was suppressed by an inhibitor of Na(+)-dependent specific glucose transporter, phrolidzin, which did not affect FD-4 permeation. These findings suggested that absorption enhancement by Sit-G NP may not be due to opening of a tight junction, but might be related to endocytosis via glucose residue of Sit-G.

  10. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice.

    PubMed

    Aslam, Mohamad F; Frazer, David M; Faria, Nuno; Bruggraber, Sylvaine F A; Wilkins, Sarah J; Mirciov, Cornel; Powell, Jonathan J; Anderson, Greg J; Pereira, Dora I A

    2014-08-01

    The ferritin core is composed of fine nanoparticulate Fe(3+) oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe(3+) polyoxohydroxide (nanoFe(3+)). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe(2+) sulfate (FeSO4), nanoFe(3+), or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe(3+) was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe(3+) are equally bioavailable in WT mice, and at wk 8 the mean ± SEM hemoglobin increase was 18 ± 7 g/L in the FeSO4 group and 30 ± 5 g/L in the nanoFe(3+) group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe(3+) is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.

  11. A role for NPC1 and NPC2 in intestinal cholesterol absorption--the hypothesis gutted.

    PubMed

    Liscum, Laura

    2007-11-15

    Dietary and biliary cholesterol are taken up by intestinal epithelial cells and transported to the endoplasmic reticulum. At the endoplasmic reticulum, cholesterol is esterified, packaged into chylomicrons and secreted into the lymph for delivery to the bloodstream. NPC1L1 (Niemann-Pick C1-like 1) is a protein on the enterocyte brush-border membrane that facilitates cholesterol absorption. Cholesterol's itinerary as it moves to the endoplasmic reticulum is unknown, as is the identity of any cellular proteins that facilitate the movement. Two proteins that play an important role in intracellular cholesterol transport and could potentially influence NPC1L1-mediated cholesterol uptake are NPC1 and NPC2 (Niemann-Pick type C disease proteins 1 and 2). In this issue of the Biochemical Journal, Dixit and colleagues show that the absence or presence of NPC1 and NPC2 has no effect on intestinal cholesterol absorption in the mouse. Thus neither protein fills the gap in our knowledge of intra-enterocyte cholesterol transport. Furthermore, the NPC1/NPC2 pathway would not be a good target for limiting the uptake of dietary cholesterol. PMID:17956226

  12. A modified physiological BCS for prediction of intestinal absorption in drug discovery.

    PubMed

    Zaki, Noha M; Artursson, Per; Bergström, Christel A S

    2010-10-01

    In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

  13. Utility and limitation of calciuric response to oral calcium load as a measure of intestinal calcium absorption: comparison with isotopic fractional calcium absorption

    SciTech Connect

    Zerwekh, J.E.; Sakhaee, K.; Pak, C.Y.

    1981-11-01

    The intestinal absorption of calcium (Ca), indirectly measured from the calciuric response to oral Ca load (1g), was compared to the more directly obtained isotopic fractional absorption, alpha (from the fecal recovery of orally administered 47Ca). In 17 normal subjects and 30 patients with absorptive hypercalciuria (AH), there was a significant (P less than 0.001) correlation of alpha with the Ca load responses, (r . 0.81). However, this correlation was not observed in patients with renal hypercalciuria (RH), and those with AH receiving thiazide or orthophosphate. In RH, 38 per cent of patients had elevated Ca load responses, despite normal values for alpha. The point correlating the calciuric response and alpha in these patients was below the 95 per cent confidence limit of the line correlating alpha and the load response. Thus, Ca load response often overestimated intestinal Ca absorption, because of the high basal (fasting) urinary Ca. Thiazide therapy in RH improved the correlation between the two tests of Ca absorption. However, thiazide therapy in AH produced normal Ca load responses despite persistently high alpha in 60 per cent of patients. Similarly, 50 per cent of patients with AH receiving orthophosphate had normal Ca load response, although alpha remained elevated. Thus, Ca load response underestimated Ca absorption when patients with AH took thiazide or orthophosphate, probably because these drugs augment renal tubular reabsorption of Ca. These data support the Ca load test as a valid indirect measure of intestinal Ca absorption in normal subjects and patients with AH, in whom fasting urinary Ca is not elevated. In conditions of renal Ca, leak or with various drugs known to alter renal Ca handling, there seen to be large deviations of Ca load response from alpha. Care should be exercised before reaching conclusions regarding the intestinal Ca absorption in these situations.

  14. Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation

    PubMed Central

    Ngo, Ha Thi; Hetland, Ragna Bogen; Nygaard, Unni Cecilie; Steffensen, Inger-Lise

    2015-01-01

    We have studied how spontaneous or carcinogen-induced intestinal tumorigenesis was affected by genetic or diet-induced obesity in C57BL/6J-ApcMin/+ X C57BL/6J-Lepob/+ mice. Obesity was induced by the obese (ob) mutation in the lep gene coding for the hormone leptin, or by a 45% fat diet. The effects of obesity were examined on spontaneous intestinal tumors caused by the multiple intestinal neoplasia (Min) mutation in the adenomatous polyposis coli (Apc) gene and on tumors induced by the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). F1 ob/ob (homozygous mutated) mice had increased body weight (bw) and number of spontaneous and PhIP-induced small intestinal tumors (in ApcMin/+ mice), versus ob/wt (heterozygous mutated) and wt/wt mice (homozygous wild-type). A 45% fat diet exacerbated bw and spontaneous tumor numbers versus 10% fat, but not PhIP-induced tumors. Except for bw, ob/wt and wt/wt were not significantly different. The obesity caused hyperglucosemia and insulinemia in ob/ob mice. A 45% fat diet further increased glucose, but not insulin. Inflammation was seen as increased TNFα levels in ob/ob mice. Thus the results implicate disturbed glucose regulation and inflammation as mechanisms involved in the association between obesity and intestinal tumorigenesis. Ob/ob mice had shorter lifespan than ob/wt and wt/wt mice. PMID:26347815

  15. Intestine.

    PubMed

    Smith, J M; Skeans, M A; Horslen, S P; Edwards, E B; Harper, A M; Snyder, J J; Israni, A K; Kasiske, B L

    2016-01-01

    Intestine and intestine-liver transplant plays an important role in the treatment of intestinal failure, despite decreased morbidity associated with parenteral nutrition. In 2014, 210 new patients were added to the intestine transplant waiting list. Among prevalent patients on the list at the end of 2014, 65% were waiting for an intestine transplant and 35% were waiting for an intestine-liver transplant. The pretransplant mortality rate decreased dramatically over time for all age groups. Pretransplant mortality was highest for adult candidates, at 22.1 per 100 waitlist years compared with less than 3 per 100 waitlist years for pediatric candidates, and notably higher for candidates for intestine-liver transplant than for candidates for intestine transplant without a liver. Numbers of intestine transplants without a liver increased from a low of 51 in 2013 to 67 in 2014. Intestine-liver transplants increased from a low of 44 in 2012 to 72 in 2014. Short-gut syndrome (congenital and other) was the main cause of disease leading to both intestine and intestine-liver transplant. Graft survival improved over the past decade. Patient survival was lowest for adult intestine-liver recipients and highest for pediatric intestine recipients.

  16. Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese.

    PubMed

    Shawki, Ali; Anthony, Sarah R; Nose, Yasuhiro; Engevik, Melinda A; Niespodzany, Eric J; Barrientos, Tomasa; Öhrvik, Helena; Worrell, Roger T; Thiele, Dennis J; Mackenzie, Bryan

    2015-10-15

    Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1(int/int)). DMT1(int/int) mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1(int/int) mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1(int/int) mice compared with DMT1(+/+) mice but no meaningful change in copper, manganese, or zinc. DMT1(int/int) mice absorbed (64)Cu and (54)Mn from an intragastric dose to the same extent as did DMT1(+/+) mice but the absorption of (59)Fe was virtually abolished in DMT1(int/int) mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc.

  17. Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese

    PubMed Central

    Shawki, Ali; Anthony, Sarah R.; Nose, Yasuhiro; Engevik, Melinda A.; Niespodzany, Eric J.; Barrientos, Tomasa; Öhrvik, Helena; Worrell, Roger T.; Thiele, Dennis J.

    2015-01-01

    Divalent metal-ion transporter-1 (DMT1) is a widely expressed iron-preferring membrane-transport protein that serves a critical role in erythroid iron utilization. We have investigated its role in intestinal metal absorption by studying a mouse model lacking intestinal DMT1 (i.e., DMT1int/int). DMT1int/int mice exhibited a profound hypochromic-microcytic anemia, splenomegaly, and cardiomegaly. That the anemia was due to iron deficiency was demonstrated by the following observations in DMT1int/int mice: 1) blood iron and tissue nonheme-iron stores were depleted; 2) mRNA expression of liver hepcidin (Hamp1) was depressed; and 3) intraperitoneal iron injection corrected the anemia, and reversed the changes in blood iron, nonheme-iron stores, and hepcidin expression levels. We observed decreased total iron content in multiple tissues from DMT1int/int mice compared with DMT1+/+ mice but no meaningful change in copper, manganese, or zinc. DMT1int/int mice absorbed 64Cu and 54Mn from an intragastric dose to the same extent as did DMT1+/+ mice but the absorption of 59Fe was virtually abolished in DMT1int/int mice. This study reveals a critical function for DMT1 in intestinal nonheme-iron absorption for normal growth and development. Further, this work demonstrates that intestinal DMT1 is not required for the intestinal transport of copper, manganese, or zinc. PMID:26294671

  18. Effects of guar gum and cellulose on glucose absorption, hormonal release and hepatic metabolism in the pig

    NASA Technical Reports Server (NTRS)

    Nunes, C. S.; Malmlof, K.

    1992-01-01

    Six Large White pigs (mean body-weight 59 (SE 1.7) kg) were surgically fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein, as well as with electromagnetic flow probes around the portal vein and the hepatic artery, and allowed to recover. The non-anaesthetized animals were given a basal non-fibre diet (diet A) alone or together with 60 g guar gum/kg (diet B) or 150 g purified cellulose/kg (diet C) by substitution for mica. The diets were given for weekly periods and according to a replicated 3 x 3 Latin square design. On the last day of each such adaptation period, test meals of 800 g were given before blood sampling. Sampling was continued for 8 h. Guar gum strongly reduced glucose apparent absorption without changing the absorption and the hepatic uptake profiles. Production rates of insulin, gastric inhibitory polypeptide and insulin-like growth factor-1 (IGF-1) were lowest after guar gum ingestion. However, the reductions in peripheral blood insulin levels caused by guar gum were not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly secreted by the gut, whereas the liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut-produced IGF-1. Guar gum ingestion appeared also to decrease glucagon secretion. Cellulose at the level consumed had very few effects on the variables considered. It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the metabolic effects described.

  19. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

    PubMed

    Lesjak, Marija; Hoque, Rukshana; Balesaria, Sara; Skinner, Vernon; Debnam, Edward S; Srai, Surjit K S; Sharp, Paul A

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin--the most abundant dietary polyphenol--are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3'UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption. PMID:25058155

  20. Quercetin Inhibits Intestinal Iron Absorption and Ferroportin Transporter Expression In Vivo and In Vitro

    PubMed Central

    Balesaria, Sara; Skinner, Vernon; Debnam, Edward S.; Srai, Surjit K. S.; Sharp, Paul A.

    2014-01-01

    Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin – the most abundant dietary polyphenol – are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3′UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption. PMID:25058155

  1. Feed supplemented with organic acids does not affect starch digestibility, nor intestinal absorptive or secretory function in broiler chickens.

    PubMed

    Ruhnke, I; Röhe, I; Goodarzi Boroojeni, F; Knorr, F; Mader, A; Hafeez, A; Zentek, J

    2015-04-01

    The current study aimed to determine the impact of acidified feed on apparent ileal starch digestibility, intestinal transport and barrier function and intestinal glucose transporter expression. The experiment included a control group and a treatment group with broilers fed a standard diet without or with 1.5% of a commercial organic acid product (64% formic acid, 25% propionic acid, 11% water). Broilers were fed with the experimental diets from hatching until days 32-35. Starch digestibility was determined using 0.2% titanium dioxide as ingestible marker. Gene expressions of the intestinal sodium glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2) were analysed using qPCR analysis. Additionally, SGLT-1 function and chloride secretion were analysed in Ussing chamber experiments. Jejunal samples were sequentially exposed to 10 mm glucose, 100 μm phloridzin, 100 μm histamine and 100 μm carbachol. Apparent ileal starch digestibility (±SEM) of the control group (97.5 ± 0.35%) and the acid-treated group (97.0 ± 0.59%) did not differ (p = 0.674). The mean tissue conductance of intestinal samples obtained from the control group and the treatment group was similar [10.6 mS/cm(2) (±0.68) and 9.4 mS/cm(2) (±0.80) respectively (p = 0.147)]. The mean short-circuit currents (ΔIsc ) of the samples exposed to glucose, phloridzin, histamine and carbachol did not differ (p > 0.05). Additionally, no differences in the expression of SGLT-1 and GLUT-2 could be observed (p = 0.942, p = 0.413). Based on this study, the consumption of feed supplemented with organic acids was not associated with effects on ileal starch digestibility and functional traits of jejunal tissues, indicating that these additives have no major impact on the small intestinal function in broilers.

  2. P-glycoprotein (P-gp)-mediated efflux limits intestinal absorption of the Hsp90 inhibitor SNX-2112 in rats.

    PubMed

    Liu, Hongming; Sun, Hua; Wu, Zhufeng; Zhang, Xingwang; Wu, Baojian

    2014-08-01

    1. The promising anticancer agent SNX-2112 (a novel Hsp90 inhibitor) is poorly bioavailable after oral administration. Here, we aim to determine the role of P-glycoprotein (P-gp) in the intestinal absorption of SNX-2112. 2. We found that SNX-2112 significantly stimulated P-gp ATPase activity in in vitro ATPase assay with a small EC50 (the half-maximal effective concentration) value of 0.32 µM. 3. In the single-pass perfused rat intestine model, absorption of SNX-2112 was not favored in the small intestine with a [Formula: see text] (the wall permeability) value of 0.38-0.64. By contrast, the compound was well absorbed in the colon with a [Formula: see text] value of 1.19. The P-gp inhibitors cyclosporine and elacridar (i.e. GF120918A) markedly enhanced SNX-2112 absorption in all four intestinal segments (i.e. duodenum, jejunum, ileum and colon) and the fold change ranged from 3.1 to 14.1. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of SNX-2112 by a 2.5-fold after oral administration. 4. This is the first report that P-gp-mediated efflux is a limiting factor for intestinal absorption of SNX-2112 in rats.

  3. Intestinal absorption of retinol and retinyl palmitate in the rat. Effects of tetrahydrolipstatin

    SciTech Connect

    Fernandez, E.; Borgstroem, B. )

    1990-09-01

    The aim of the present study was to characterize the intestinal absorption of retinol and retinyl palmitate in thoracic duct and bile duct fistulated rats and to investigate the effect of a simultaneously administered lipase inhibitor, tetrahydrolipstatin (THL). Absorption was determined as lymphatic recovery over a 24-hr period, including an initial 12-hr continuous intraduodenal infusion of either (11,12-3H)retinol or (11,12-3H)retinyl palmitate given in emulsified glyceryl trioleate or in mixed micellar solution of monoolein and oleic acid. From micellar dispersion, labeled retinol and retinyl palmitate were recovered in the lymph to 50-60% and both to the same extent. Administered in emulsified form, labeled retinol from fed retinyl palmitate was recovered to 47%, but retinol from fed retinol to only 18%. THL (10(-4) M) in the infusate had no significant effect on the recovery of 14C-labeled oleic acid. The recovery of label from emulsified glyceryl tri(1-14C)oleate was significantly decreased at this concentration of THL (76.5% vs 19.6% recovery). When administered in emulsified form, retinol absorption was not significantly affected by THL at 10(-4) M, while retinyl palmitate absorption was very significantly decreased (5.0% compared to 47.8%). In the presence of THL, retinol absorption from retinyl palmitate in micellar solution was decreased (from 58% to 17%). Most of the retinol in the lymph extracts (72.2 to 91.3) was present as retinyl ester, regardless of the chemical and physical form of administration. Furthermore, THL did not induce any change in this pattern.

  4. Calcium regulating hormones in healthy elderly men: relation to intestinal calcium absorption.

    PubMed

    Ravaglia, G; Forti, P; Maioli, F; Scali, R C; Boschi, F; Pratelli, L; Pizzoferrato, A

    1994-12-01

    Aged male subjects often have osteoporosis and it has been suggested that the cause is an age-related lack of vitamin D. We evaluated the calcium regulating endocrine mechanism in healthy aged males in order to verify this hypothesis. We studied serum levels of PTH and 1,25(OH)2D in relation to intestinal calcium absorption, radial bone mass density (BMD) and osteocalcin plasma levels in 30 healthy elderly men (61-88 yr.). 1,25(OH)2D levels and calcium absorption, assessed by oral strontium test, did not change with age with respect to a young control group. PTH was higher (p < 0.02) in the elderly than in the control group, and correlated positively with nephrogenous cAMP levels (p < 0.01; r = 0.65). Radial BMD (measured by single photon absorptiometry) was lower (p < 0.01) in elderly than in young subjects and negatively correlated with age (p < 0.01; r = -0.45). Osteocalcin levels, used as a mark of bone turnover, were unchanged. The data suggest that decreased 1,25(OH)2D levels are not a feature of normal male aging. Senile hyperparathyroidism could compensate for impairments in endogenous metabolism of vitamin D in elderly males and maintain calcium absorption at an efficient level, without increasing bone turnover. PMID:7748532

  5. The Relation between Peristaltic and Segmental Contraction, Mixing, and Absorption in the Small Intestine

    NASA Astrophysics Data System (ADS)

    Banco, Gino; Brasseur, James; Wang, Yanxing; Ailiani, Amit; Neuberger, Thomas; Webb, Andrew

    2009-11-01

    The physiology and mechanics of the small intestine originates with lumen-scale fluid motions generated by enterically controlled muscle wall contractions. Although complex in appearance, we have shown with principle component decomposition of gut motion from a rat model that simpler component structure may integrate to produce basic peristaltic and segmental motions. To couple these measured modes with fluid mixing and nutrient absorption we have developed 2-D and axisymmetric models of the gut using the lattice-Boltzmann framework with scalar and second order moving boundary conditions. Previous models indicated that peristalsis is detrimental to absorption and therefore that gut motility is likely bimodal, transitioning between peristalsis and segmental modes to optimize the transport of chyme vs. nutrient absorption. However we have since discovered that more complex control is possible due to potential transitions between ``trapped'' vs. ``nontrapped'' peristaltic fluid motions, depending on occlusion ratio. These transitions lead to an important distinction between 2-D and axisymmetric models and indicate that gut motility may be more finely controlled than previously thought. [Supported by NSF

  6. [Evaluation on intestinal absorption of alkaloids extracted by different methods from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs].

    PubMed

    Chen, Kai; Wang, Yue-liang; Chen, Yan; Li, Hui; Liu, Yu-ling; Wang, Jia-qi; Zhang, Xiao-li; Liu, Wen-cong

    2015-12-01

    The research aimed to evaluate the intestinal absorption of alkaloids extracted by decoction and alcohol extraction proces- ses from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs. Berberine, palmatine, coptisine and epiberberine were the main alkaloids in this herbal pair and taken as the standard indexes in the quantitative analysis with multi-components by single marker (QAMS) method, in order to calculate absorption rate constant (Ka) and evaluate intestinal absorption characteristics of these four alkaloids extracted by different extraction methods in different intestinal segments in rats. The results showed that the four alkaloids extracted by two different processes in high, medium and low doses had linear absorption properties in the small intestine segment, which conformed to zero-order absorption rate, intestinal segment than 0.99. The absorption rate constant (Ka) of decoction group was higher than that of alcohol extraction group.

  7. [Evaluation on intestinal absorption of alkaloids extracted by different methods from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs].

    PubMed

    Chen, Kai; Wang, Yue-liang; Chen, Yan; Li, Hui; Liu, Yu-ling; Wang, Jia-qi; Zhang, Xiao-li; Liu, Wen-cong

    2015-12-01

    The research aimed to evaluate the intestinal absorption of alkaloids extracted by decoction and alcohol extraction proces- ses from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs. Berberine, palmatine, coptisine and epiberberine were the main alkaloids in this herbal pair and taken as the standard indexes in the quantitative analysis with multi-components by single marker (QAMS) method, in order to calculate absorption rate constant (Ka) and evaluate intestinal absorption characteristics of these four alkaloids extracted by different extraction methods in different intestinal segments in rats. The results showed that the four alkaloids extracted by two different processes in high, medium and low doses had linear absorption properties in the small intestine segment, which conformed to zero-order absorption rate, intestinal segment than 0.99. The absorption rate constant (Ka) of decoction group was higher than that of alcohol extraction group. PMID:27245034

  8. Deoxynivalenol as a contaminant of broiler feed: intestinal development, absorptive functionality, and metabolism of the mycotoxin.

    PubMed

    Yunus, A W; Blajet-Kosicka, A; Kosicki, R; Khan, M Z; Rehman, H; Böhm, J

    2012-04-01

    Deoxynivalenol (DON) has been recently documented to deteriorate intestinal morphology in chickens at dietary doses that are regarded as safe for this species. The present trial was conducted to explore the significance of these morphological changes in relation to intestinal absorptive functionality and DON metabolism. Ross broilers at 7 d of age were fed either a basal diet (0.265 ± 0.048 mg of DON/kg; 0.013 ± 0.001 mg of zearalenone/kg), a low DON diet (1.68 mg of DON/kg; 0.145 ± 0.007 mg of zearalenone/kg), or a high DON diet (12.209 ± 1.149 mg of DON/kg; 1.094 ± 0.244 mg of zearalenone/kg). The DON diets (to variable degrees) progressively decreased the relative density (weight:length) of the small intestine with increasing exposure length, which could be correlated with a decrease in villus height in the small intestine. Short circuit current of the jejunal epithelium, reflecting transport function of the epithelium per unit area, was reduced (P = 0.001) in the birds fed the high DON diet. The increasing dietary level of DON linearly (P = 0.035) increased the length of the jejunum in wk 4 of exposure, resulting in conservation of macronutrient retention. Upon challenging the birds with a fixed amount of DON after wk 5 of exposure, higher (P ≤ 0.033) amounts of DON and the detoxification metabolite (de-epoxy-DON) were found at 5 h postchallenge in the guts of birds raised on the DON diets. The increasing level of previous exposure to DON linearly (P = 0.040) decreased the plasma level of DON in the birds at 1 h postchallenge. The amounts of zearalenone and its analogs in the gut and plasma also followed a trend similar to that for DON. These data suggest that intestines in chickens may adapt to a chronic DON challenge by morphological and functional modifications. The birds having previous exposure to Fusarium mycotoxins showed moderate detoxification coupled with reduced transfer of the mycotoxins to systemic circulation. Some metabolites of

  9. In situ intestinal absorption behaviors of tanshinone IIA from its inclusion complex with hydroxypropyl-beta-cyclodextrin.

    PubMed

    Ling, Wang; Rui, Li Chen; Hua, Jiang Xue

    2007-10-01

    In this paper, the intestinal permeability of the inclusion complex of tanshinone IIA (TS IIA) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated. The corresponding complexation of TS IIA-HP-beta-CD was obtained by coevaporation and characterized by differential scanning calorimetry and X-ray diffraction. The recirculation intestinal perfusion technique in rats was used to study the absorption behavior of free and complexed TS IIA. The change of concentration of TS IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate its absorption rate-limiting step. Using the mathematical models above, it was concluded that the limit step to absorption of TS IIA was the dissolution process. Different concentrations of complexed TS IIA were administrated to three intestinal segments, with the intestinal permeability ranging from 3.16x10(-5) cm.s(-1) in the duodenum (50 microg.ml(-1)) to 4.11x10(-5) cm.s(-1) in the jejunum (100 microg.ml(-1)). With the increase of dosage of complex, TS IIA's absorption did not show saturated phenomenon, suggesting its transport mechanism in vivo might primary be passive transport. Besides, the permeability of TS IIA was not apparently influenced by the perfusion section studied, which indicated that there might not exist specific absorption site for TS IIA.

  10. In situ intestinal absorption behaviors of tanshinone IIA from its inclusion complex with hydroxypropyl-beta-cyclodextrin.

    PubMed

    Ling, Wang; Rui, Li Chen; Hua, Jiang Xue

    2007-10-01

    In this paper, the intestinal permeability of the inclusion complex of tanshinone IIA (TS IIA) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated. The corresponding complexation of TS IIA-HP-beta-CD was obtained by coevaporation and characterized by differential scanning calorimetry and X-ray diffraction. The recirculation intestinal perfusion technique in rats was used to study the absorption behavior of free and complexed TS IIA. The change of concentration of TS IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate its absorption rate-limiting step. Using the mathematical models above, it was concluded that the limit step to absorption of TS IIA was the dissolution process. Different concentrations of complexed TS IIA were administrated to three intestinal segments, with the intestinal permeability ranging from 3.16x10(-5) cm.s(-1) in the duodenum (50 microg.ml(-1)) to 4.11x10(-5) cm.s(-1) in the jejunum (100 microg.ml(-1)). With the increase of dosage of complex, TS IIA's absorption did not show saturated phenomenon, suggesting its transport mechanism in vivo might primary be passive transport. Besides, the permeability of TS IIA was not apparently influenced by the perfusion section studied, which indicated that there might not exist specific absorption site for TS IIA. PMID:17917262

  11. Impact of murine intestinal apolipoprotein A-IV expression on regional lipid absorption, gene expression, and growth

    PubMed Central

    Simon, Trang; Cook, Victoria R.; Rao, Anuradha; Weinberg, Richard B.

    2011-01-01

    Apolipoprotein A-IV (apoA-IV) is synthesized by intestinal enterocytes during lipid absorption and secreted into lymph on the surface of nascent chylomicrons. A compelling body of evidence supports a central role of apoA-IV in facilitating intestinal lipid absorption and in regulating satiety, yet a longstanding conundrum is that no abnormalities in fat absorption, feeding behavior, or weight gain were observed in chow-fed apoA-IV knockout (A4KO) mice. Herein we reevaluated the impact of apoA-IV expression in C57BL6 and A4KO mice fed a high-fat diet. Fat balance and lymph cannulation studies found no effect of intestinal apoA-IV gene expression on the efficiency of fatty acid absorption, but gut sac transport studies revealed that apoA-IV differentially modulates lipid transport and the number and size of secreted triglyceride-rich lipoproteins in different anatomic regions of the small bowel. ApoA-IV gene deletion increased expression of other genes involved in chylomicron assembly, impaired the ability of A4KO mice to gain weight and increase adipose tissue mass, and increased the distal gut hormone response to a high-fat diet. Together these findings suggest that apoA-IV may play a unique role in integrating feeding behavior, intestinal lipid absorption, and energy storage. PMID:21840868

  12. Evidence of Absorptive Function in vivo in a Neo-Formed Bio-Artificial Intestinal Segment Using a Rodent Model.

    PubMed

    Cicalese, Luca; Corsello, Tiziana; Stevenson, Heather L; Damiano, Giuseppe; Tuveri, Massimiliano; Zorzi, Daria; Montalbano, Mauro; Shirafkan, Ali; Rastellini, Cristiana

    2016-01-01

    A promising therapeutic approach for intestinal failure consists in elongating the intestine with a bio-engineered segment of neo-formed autologous intestine. Using an acellular biologic scaffold (ABS), we, and others, have previously developed an autologous bio-artificial intestinal segment (BIS) that is morphologically similar to normal bowel in rodents. This neo-formed BIS is constructed with the intervention of naïve stem cells that repopulate the scaffold in vivo, and over a period of time, are transformed in different cell populations typical of normal intestinal mucosa. However, no studies are available to demonstrate that such BIS possesses functional absorptive characteristics necessary to render this strategy a possible therapeutic application. The aim of this study was to demonstrate that the BIS generated has functional absorptive capacity. Twenty male August × Copenhagen-Irish (ACI) rats were used for the study. Two-centimeter sections of ABS were transplanted in the anti-mesenteric border of the small bowel. Animals were studied at 4, 8, and 12 weeks post-engraftment. Segments of intestine with preserved vascular supply and containing the BIS were isolated and compared to intestinal segments of same length in sham control animals (n = 10). D-Xylose solution was introduced in the lumen of the intestinal segments and after 2 h, urine and blood were collected to evaluate D-Xylose levels. Quantitative analysis was performed using ELISA. Morphologic, ultrastructural, and indirect functional absorption analyses were also performed. We observed neo-formed intestinal tissue with near-normal mucosa post-implantation as expected from our previously developed model. Functional characteristics such as morphologically normal enterocytes (and other cell types) with presence of brush borders and preserved microvilli by electron microscopy, preserved water, and ion transporters/channels (by aquaporin and cystic fibrosis transmembrane conductance regulator

  13. Effects of glucose and ascorbic acid on absorption and first pass metabolism of isoniazid in rats.

    PubMed

    Matsuki, Y; Katakuse, Y; Matsuura, H; Kiwada, H; Goromaru, T

    1991-02-01

    We examined the effect of glucose (Glu) and ascorbic acid (AA) on absorption and metabolism of isoniazid (INAH). After p.o. administration of INAH with or without Glu or AA, plasma concentration and urinary excretion of INAH and its metabolites, acetyl INAH (AcINAH), acetyl hydrazine (AcHy) and hydrazine (Hy), were determined by means of gas chromatography-mass spectrometry using stable isotope labeled compounds as internal standard. The combined administration of INAH with Glu or AA led to a significant decrease in the excretion of INAH and Hy, and a significant increase in the excretion of AcINAH and AcHy. The absorption amount of INAH was reduced to about one-half by the addition of Glu and the absorption rate of INAH markedly decreased in the case of co-administration of AA. Comparing the oral case with the results of i.v. administration, Glu and AA only affect the absorption process containing the first pass metabolism of INAH.

  14. Intestinal absorption of amino acids in the Pacific bluefin tuna (Thunnus orientalis): in vitro lysine-arginine interaction using the everted intestine system.

    PubMed

    Martínez-Montaño, Emmanuel; Peña, Emyr; Viana, María Teresa

    2013-04-01

    The interaction between lysine (Lys) and arginine (Arg) in the proximal intestinal region of Pacific bluefin tuna (Thunnus orientalis) was evaluated using the everted intestine method. This in vitro intestinal system has been shown to be an effective tool for studying the nutrient absorption without the need to handle the tuna fish in marine cages as needed for digestibility and amino acid (AA) absorption. We used a factorial design with two sets of variables: low and high Lys concentration (10 and 75 mM) and four different Arg concentrations (3, 10, 20, and 30 mM). Both amino acids were dissolved in marine Ringer solution with a basal amino acidic composition consisting of a tryptone solution (9 mg mL(-1)). No interaction was observed between the absorption of Lys and Arg during the first 10 min of the experiment when low concentration of Lys and Arg was used in the hydrolyzate solution. However, there seemed to be a positive effect on Lys absorption when both amino acids were at high concentrations (30 and 75 mM, respectively). This type of studies will led us to test different formulations and/or additives to better understand the efficiency of AA supplementation as an alternative to in situ studies that are difficult to follow to design with the Pacific Bluefin Tuna.

  15. [Rat intestine absorption kinetics study on cucurbitacin B-sodium deoxycholate/phospholipid mixed nanomicelles with in vitro everted gut sacs model].

    PubMed

    Cheng, Ling; Shen, Bao-de; Li, Juan-juan; Qiu, Ling; Shen, Gang; Zhang, Li-hong; Han, Jin; Yuan, Hai-long

    2015-07-01

    To investigate the absorption kinetics of Cu B-SDC/PLC-MMs in rat different intestinal segments and compared with the absorption of Cu B suspension. The in vitro everted gut sacs model was established to study the absorption characteristics of Cu B-SDC/ PLC-MMs in rat duodenum, jejunum, ileum and colon, and the content of cucurbitacin B was detected by HPLC method, and the effects of concentrations on intestinal absorption were evaluated as well. The results showed that the absorption of Cu B-SDC/PLC-MMs was linearity at different intestine segment and different concentrations (R2 > 0.9), which was consistent with zero order rate process. The Ka of different intestine segments showed a concentration-dependent increasing along with the raised concentration of Cu B-SDC/ PLC-MMs, indicating that it was likely to be a mechanism of passive absorption. The best absorption site of Cu B-SDC/PLC-MMs was ileum, and its absorptions in different intestinal segments were superior to cucurbitacin B suspension. SDC/PLC-MMs could significantly enhance the intestinal absorption of cucurbitacin B, and the study of intestinal absorption kinetics of Cu B-SDC/PLC-MMs had gave a support to its further reasonable solidfication.

  16. Prevention of cholesterol gallstones by inhibiting hepatic biosynthesis and intestinal absorption of cholesterol

    PubMed Central

    Wang, Helen H; Portincasa, Piero; de Bari, Ornella; Liu, Kristina J; Garruti, Gabriella; Neuschwander-Tetri, Brent A; Wang, David Q.-H

    2013-01-01

    Cholesterol cholelithiasis is a multifactorial disease influenced by a complex interaction of genetic and environmental factors, and represents a failure of biliary cholesterol homeostasis in which the physical-chemical balance of cholesterol solubility in bile is disturbed. The primary pathophysiologic event is persistent hepatic hypersecretion of biliary cholesterol, which has both hepatic and small intestinal components. The majority of the environmental factors are probably related to Western-type dietary habits, including excess cholesterol consumption. Laparoscopic cholecystectomy, one of the most commonly performed surgical procedures in the US, is nowadays a major treatment for gallstones. However, it is invasive and can cause surgical complications, and not all patients with symptomatic gallstones are candidates for surgery. The hydrophilic bile acid, ursodeoxycholic acid (UDCA) has been employed as first-line pharmacological therapy in a subgroup of symptomatic patients with small, radiolucent cholesterol gallstones. Long-term administration of UDCA can promote the dissolution of cholesterol gallstones. However, the optimal use of UDCA is not always achieved in clinical practice because of failure to titrate the dose adequately. Therefore, the development of novel, effective, and noninvasive therapies is crucial for reducing the costs of health care associated with gallstones. In this review, we summarize recent progress in investigating the inhibitory effects of ezetimibe and statins on intestinal absorption and hepatic biosynthesis of cholesterol, respectively, for the treatment of gallstones, as well as in elucidating their molecular mechanisms by which combination therapy could prevent this very common liver disease worldwide. PMID:23419155

  17. Gastric emptying and intestinal absorption of ingested water and saline by hypovolemic rats.

    PubMed

    Stricker, Edward M; Bykowski, Michael R; Hossler, Carrie A Smith; Curtis, Kathleen S; Smith, James C

    2009-12-01

    Recent experiments showed that in a one-bottle test conducted 16h after sc injection of polyethylene glycol (PEG) solution, hypovolemic rats consumed water or 0.30 M NaCl in an initial drinking episode but did not empty the ingested fluid from the stomach or absorb it from the small intestine very rapidly, certainly not as rapidly as when 0.15M NaCl was consumed (Smith et al., Am J Physiol 292: R2089-R2099, 2007). The present experiments examined the patterns of water and 0.30 M NaCl ingestion and the movement of consumed fluid through the gastrointestinal tract when PEG-treated rats were given a two-bottle delayed-access test. We found that both fluids always were consumed in the first drinking episode, that the fluid mixture ingested was equivalent to 0.10-0.15M NaCl, and that gastric emptying rate and net fluid absorption from the small intestine usually were much faster than when PEG-treated rats drank either water or hypertonic saline alone. Thus, ingestion of water and 0.30 M NaCl by hypovolemic rats in the same episode adaptively facilitated the movement into the circulation of a near-isotonic fluid that is ideal for restoring plasma volume deficits.

  18. Inhibition of goby posterior intestinal NaCl absorption by natriuretic peptides and by cardiac extracts.

    PubMed

    Loretz, C A

    1996-01-01

    Natriuretic peptides abolish active Na+ and Cl- absorption across the posterior intestine of the euryhaline goby Gillichthys mirabilis. Inhibition by eel and human natriuretic peptides is dose-dependent with the following sequence of potencies based on experimentally determined ID50 values for inhibition of short-circuit current: eel ventricular natriuretic peptide (78 nmol.l-1), eel atrial natriuretic peptide (156 nmol.l-1), human brain natriuretic peptide (326 nmol.l-1), human alpha atrial natriuretic peptide (1.05 mumol.l-1), and eel C-type natriuretic peptide (75 mumol.l-1). Natriuretic peptides also significantly increase transcellular conductance. The observed sequence of natriuretic peptide potencies is suggestive of cellular mediation by GC-A-type NP-R1 receptors in this tissue; as expected for guanylyl-cyclase-coupled NP-R1 receptors, cyclic GMP mimics the action of natriuretic peptides on the goby intestine. Crude aqueous extracts of goby atrium and ventricle inhibited short circuit current and increased tissue conductance in a dose-dependent manner. Ventricular extract was more potent than atrial extract on both a per organ and per milligram basis.

  19. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status.

    PubMed

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-08-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2 D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m(2)). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2 D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = -0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to

  20. An electron microscopic study of the intestinal villus. II. The pathway of fat absorption.

    PubMed

    PALAY, S L; KARLIN, L J

    1959-05-25

    The intestinal pathway for absorbed fat was traced in thin sections of intestinal villi from rats fed corn oil by stomach tube after a fast of 24 to 40 hours. For electron microscopy the tissues were fixed in chilled buffered osmium tetroxide and embedded in methacrylate. For light microscopy, other specimens from the same animals were fixed in formal-calcium, mordanted in K(2)Cr(2)O(7), and embedded in gelatin. Frozen sections were stained with Sudan black B or Sudan IV. About 20 minutes after feeding, small fat droplets (65 mmicro maximal diameter) appear in the striated border between microvilli. At the same time fat particles are seen within pinocytotic vesicles in the immediately subjacent terminal web. In later specimens the fat droplets are generally larger (50 to 240 mmicro) and lie deeper in the apical cytoplasm. All intracellular fat droplets are loosely enveloped in a thin membrane, the outer surface of which is sometimes studded with the fine particulate component of the cytoplasm. This envelope, apparently derived from the cell surface by pinocytosis, has at this stage evidently become a part of the endoplasmic reticulum. Just above the nucleus numerous fat droplets lie clustered within the dilated cisternae of the Golgi complex. As absorption progresses fat droplets appear in the intercellular spaces of the epithelium, in the interstitial connective tissue spaces of the lamina propria, and in the lumen of the lacteals. All of these extracellular fat droplets are devoid of a membranous envelope. The picture of fat absorption as reconstructed from these studies involves a stream of fat droplets filtering through the striated border, entering the epithelial cell by pinocytosis at the bases of the intermicrovillous spaces, and coursing through the endoplasmic reticulum to be discharged at the sides of the epithelial cell into extracellular spaces. From the epithelial spaces, the droplets move into the lamina propria and thence into the lymph. If the lumen

  1. Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status

    PubMed Central

    Schafer, Anne L; Weaver, Connie M; Black, Dennis M; Wheeler, Amber L; Chang, Hanling; Szefc, Gina V; Stewart, Lygia; Rogers, Stanley J; Carter, Jonathan T; Posselt, Andrew M; Shoback, Dolores M; Sellmeyer, Deborah E

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2D-mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m2). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6-month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24-hour urinary Ca decreased, PTH increased, and 1,25(OH)2D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = −0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to the decline in BMD after RYGB, and strategies to

  2. Glucose and galactose absorption after ingestion of milk containing hydrolysed lactose in calves with diarrhoea.

    PubMed

    Gutzwiller, A

    2000-10-01

    Ten calves which had contracted acute diarrhoea caused by rotavirus, coronavirus and Cryptosporidium were used to test the hypothesis that feeding lactose-hydrolysed cow's milk instead of unprocessed cow's milk improves sugar absorption in diarrhoeic calves. The animals were rehydrated with an orally administered solution containing electrolytes and glucose. Thereafter the calves received one test meal of whole fresh cow's milk whose lactose had been hydrolysed by added lactase and one test meal of unprocessed cow's milk at an interval of 24 h in a cross-over design trial. In comparison with unprocessed milk, the intake of milk containing hydrolysed lactose resulted in a slight decrease of mean breath hydrogen concentration (P = 0.18), but also a slight decrease of mean blood galactose concentration (P = 0.14). There was no treatment effect on mean plasma glucose concentration. Peak plasma glucose and blood galactose concentration tended to be delayed after the intake of lactose-hydrolysed milk, which implies that gastric emptying was probably delayed. The results show that feeding milk which contains hydrolysed lactose does not significantly improve lactose utilization in calves that are suffering from benign infectious diarrhoea.

  3. Absorption and disposition of naringenin and quercetin after simultaneous administration via intestinal perfusion in mice.

    PubMed

    Orrego-Lagarón, Naiara; Martínez-Huélamo, Miriam; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Escribano-Ferrer, Elvira

    2016-09-14

    As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites.

  4. Absorption and disposition of naringenin and quercetin after simultaneous administration via intestinal perfusion in mice.

    PubMed

    Orrego-Lagarón, Naiara; Martínez-Huélamo, Miriam; Quifer-Rada, Paola; Lamuela-Raventos, Rosa M; Escribano-Ferrer, Elvira

    2016-09-14

    As common constituents of tomatoes and other fruits and/or vegetables, naringenin and quercetin are usually ingested together, so for a clearer understanding of their bioavailability, metabolic fates and health benefits, it is more insightful to study them together. The purpose of the present work was to study how co-administration of naringenin and quercetin at realistic doses (3.5 μg ml(-1) and 2.36 μg ml(-1), respectively) influences their absorption and intestinal first-pass metabolism. A single-pass intestinal perfusion model in mice (n = 4-6) was used. Perfusate (every 10 minutes), blood (at 60 min) and bile samples were analysed by an UPLC-ESI-MS/MS method to evaluate the presence of the aglycones and their metabolites. Both naringenin and quercetin showed high permeability coefficients when administered separately (7.71 ± 0.82 × 10(-4) cm s(-1)vs. 7.30 ± 1.95 × 10(-4) cm s(-1), respectively), but these values decreased by 50% with co-administration (4.09 ± 0.89 × 10(-4) cm s(-1) for naringenin and 3.18 ± 0.45 × 10(-4) cm s(-1) for quercetin). Moreover, the level of phase II metabolites in perfusion, plasma and bile samples increased when naringenin and quercetin were administered together. The higher biliary excretion of these metabolites could thus favour the entero-hepatic recycling of the aglycones and metabolites. The results of this study may have several useful applications: to know and consider the possible interactions between polyphenols and drugs that use the same mechanism of absorption and elimination; when polyphenol-rich nutritional supplements are supplied, and in our regular diets to optimize the health benefits afforded by the biological activities of such aglycones and/or metabolites. PMID:27515345

  5. Region-dependent absorption of faropenem shared with foscarnet, a phosphate transporter substrate, in the rat small intestine.

    PubMed

    Saitoh, Hiroshi; Sawazaki, Rinako; Oda, Masako; Kobayashi, Michiya

    2008-09-01

    Faropenem, a penem antibiotic, is orally active despite its hydrophilic nature. However, its intestinal absorption has not yet been characterised in detail. This study was undertaken to determine the factors regulating faropenem absorption using intestinal loops prepared in the rat duodenum, jejunum and terminal ileum. Faropenem disappearance was much greater than that of cefotaxime and meropenem, and faropenem disappeared more extensively from the terminal ileum than from the jejunum or duodenum. In contrast to faropenem, the disappearance of ceftibuten was much greater from the duodenum and jejunum than from the terminal ileum. As the accumulation and enzymatic degradation of faropenem was minimal in the intestinal mucosa, faropenem was considered to enter the portal vein smoothly after its disappearance from the intestinal loops. Faropenem disappearance was not significantly influenced by the presence of monocarboxylic acids, amino acids or bile acid. Dipeptides such as L-carnosine and glycylglycine slightly but significantly lowered faropenem disappearance from the terminal ileum. On the other hand, foscarnet exerted a marked inhibitory effect on faropenem disappearance, but the antiviral agent did not modulate ceftibuten absorption. The present results suggest that faropenem is in part absorbed via a phosphate transporter present in the rat small intestine. PMID:18614339

  6. Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition.

    PubMed

    Alqahtani, Saeed; Qosa, Hisham; Primeaux, Brian; Kaddoumi, Amal

    2015-09-01

    The known mechanism by which orlistat decreases the absorption of dietary cholesterol is by inhibition of intestinal lipases. The aim of this study was to investigate the ability of orlistat to limit cholesterol absorption by inhibition of the cholesterol transport protein Niemann-Pick C1-like 1 (NPC1L1) as another mechanism of action. In situ rat intestinal perfusion studies were conducted to study the effect of orlistat on jejunal cholesterol absorption. Inhibition kinetic parameters were calculated from in vitro inhibition studies using Caco2 and NPC1L1 transfected cell lines. The in situ studies demonstrated that intestinal perfusion of orlistat (100µM) was able to reduce cholesterol absorption by three-fold when compared to control (i.e. in the absence of orlistat, P<0.01). In vitro studies using Caco2 cells demonstrated orlistat to reduce the cellular uptake of cholesterol by 30%. Additionally, orlistat reduced the cellular uptake of cholesterol in dose dependent manner in NPC1L1 transfected cell line with an IC50=1.2µM. Lineweaver-Burk plot indicated a noncompetitive inhibition of NPC1L1 by orlistat. Beside the already established mechanism by which orlistat reduces the absorption of cholesterol, we demonstrated for the first time that orlistat limits cholesterol absorption by the inhibition of NPC1L1 transport protein.

  7. Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.

    PubMed

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam

    2016-01-15

    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption. PMID:26577021

  8. Folate-binding protein and the absorption of folic acid in the small intestine of the suckling rat

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1988-09-01

    The folate in milk is largely bound to high-affinity folate-binding protein (FBP). With an in vivo intestinal loop technique, we examined the absorption of folic acid bound to FBP (FA-FBP) in the small intestine of the suckling rat. In contrast to unbound folic acid (FA), FA-FBP is absorbed more avidly in the ileum than in the jejunum (p less than 0.025) and its absorption is not inhibited by 1 mmol sulfasalazine/L. Folate-binding activities in the mucosa of the proximal (duodenum and jejunum combined) and distal (ileum) small intestine were also examined and found to be 0.32 and 1.31 pmol/mg protein, respectively (p less than 0.001). A 6-h fast produced a 42% decrease in folate-binding activity in the distal small intestine (p less than 0.01) but did not change activity in the proximal portion. Collectively, these observations suggest that FA-FBP is absorbed by a mechanism that is distinct from that responsible for the absorption of FA and that absorption does not require prior dissociation of the vitamin-binding protein complex.

  9. Effect of cadmium administration on intestinal calcium absorption and vitamin D-dependent calcium-binding protein

    SciTech Connect

    Fullmer, C.S.; Oku, T.; Wasserman, R.H.

    1980-08-01

    The effects of cadmium on intestinal calcium absorption and calcium-binding protein (CaBP) were investigated in chicks by means of the in situ ligated duodenal loop technique. Dietary cadmium, administered in the feed or by gastric intubation, resulted in significant declines in intestinal calcium absorption and mucosal calcium-binding protein concentrations. Cadmium chloride injected directly into the ligated loop of naive chicks also diminished calcium absorption and CaBP concentrations in an apparently dose-response related fashion. No adverse effects of cadmium administration on either the 25- or 1..cap alpha..-hydroxylation reactions of vitamin D were observed. While the general effect of cadmium administration was a reduction in intestinal calcium absorption, plasma calcium levels were consistently elevated in Cd-treated chicks, with the exception of those also maintained on diets low in Ca. The results indicate that cadmium toxicity exerts at least two effects on Ca metabolism, one at the intestinal level and another at the level of the bone, kidney, or both.

  10. Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.

    PubMed

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam

    2016-01-15

    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption.

  11. Low Zinc Status and Absorption Exist in Infants with Jejunostomies or Ileostomies Which Persists after Intestinal Repair

    PubMed Central

    Balay, Kimberly S.; Hawthorne, Keli M.; Hicks, Penni D.; Chen, Zhensheng; Griffin, Ian J.; Abrams, Steven A.

    2012-01-01

    There is very little data regarding trace mineral nutrition in infants with small intestinal ostomies. Here we evaluated 14 infants with jejunal or ileal ostomies to measure their zinc absorption and retention and biochemical zinc and copper status. Zinc absorption was measured using a dual-tracer stable isotope technique at two different time points when possible. The first study was conducted when the subject was receiving maximal tolerated feeds enterally while the ostomy remained in place. A second study was performed as soon as feasible after full feeds were achieved after intestinal repair. We found biochemical evidence of deficiencies of both zinc and copper in infants with small intestinal ostomies at both time points. Fractional zinc absorption with an ostomy in place was 10.9% ± 5.3%. After reanastamosis, fractional zinc absorption was 9.4% ± 5.7%. Net zinc balance was negative prior to reanastamosis. In conclusion, our data demonstrate that infants with a jejunostomy or ileostomy are at high risk for zinc and copper deficiency before and after intestinal reanastamosis. Additional supplementation, especially of zinc, should be considered during this time period. PMID:23112915

  12. Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicor...

  13. Lipid absorption defects in intestine-specific microsomal triglyceride transfer protein and ATP-binding cassette transporter A1-deficient mice.

    PubMed

    Iqbal, Jahangir; Parks, John S; Hussain, M Mahmood

    2013-10-18

    We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92-95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations.

  14. Dietary I(-) absorption: expression and regulation of the Na(+)/I(-) symporter in the intestine.

    PubMed

    Nicola, Juan Pablo; Carrasco, Nancy; Masini-Repiso, Ana María

    2015-01-01

    Thyroid hormones are critical for the normal development, growth, and functional maturation of several tissues, including the central nervous system. Iodine is an essential constituent of the thyroid hormones, the only iodine-containing molecules in vertebrates. Dietary iodide (I(-)) absorption in the gastrointestinal tract is the first step in I(-) metabolism, as the diet is the only source of I(-) for land-dwelling vertebrates. The Na(+)/I(-) symporter (NIS), an integral plasma membrane glycoprotein located in the brush border of enterocytes, constitutes a central component of the I(-) absorption system in the small intestine. In this chapter, we review the most recent research on structure/function relations in NIS and the protein's I(-) transport mechanism and stoichiometry, with a special focus on the tissue distribution and hormonal regulation of NIS, as well as the role of NIS in mediating I(-) homeostasis. We further discuss recent findings concerning the autoregulatory effect of I(-) on I(-) metabolism in enterocytes: high intracellular I(-) concentrations in enterocytes decrease NIS-mediated uptake of I(-) through a complex array of posttranscriptional mechanisms, e.g., downregulation of NIS expression at the plasma membrane, increased NIS protein degradation, and reduction of NIS mRNA stability leading to decreased NIS mRNA levels. Since the molecular identification of NIS, great progress has been made not only in understanding the role of NIS in I(-) homeostasis but also in developing protocols for NIS-mediated imaging and treatment of various diseases.

  15. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    PubMed Central

    Coudray, Charles; Rambeau, Mathieu; Feillet-Coudray, Christine; Tressol, Jean Claude; Demigne, Christian; Gueux, Elyett; Mazur, Andrzej; Rayssiguier, Yves

    2005-01-01

    Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans. PMID:16253138

  16. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

    PubMed

    Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radović, Nikola; Jadrijević, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Sabolić, Ivan; Koepsell, Hermann

    2015-09-01

    Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.

  17. Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.

    PubMed

    Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radović, Nikola; Jadrijević, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Sabolić, Ivan; Koepsell, Hermann

    2015-09-01

    Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development. PMID:25304002

  18. Intestinal absorption, blood transport and hepatic and muscle metabolism of fatty acids in preruminant and ruminant animals.

    PubMed

    Hocquette, J F; Bauchart, D

    1999-01-01

    Current research on lipid metabolism in ruminants aims to improve the growth and health of the animals and the muscle characteristics associated with meat quality. This review, therefore, focuses on fatty acid (FA) metabolism from absorption to partitioning between tissues and metabolic pathways. In young calves, which were given high-fat milk diets, lipid absorption is delayed because the coagulation of milk caseins results in the retention of dietary fat as an insoluble clot in the abomasum. After weaning, the calves were fed forage- and cereal-based diets containing low levels of long-chain fatty acids (LCFA) but leading to high levels of volatile fatty acid (VFA) production by the rumen microflora. Such differences in dietary FA affect: i) the lipid transport system via the production of lipoproteins by the intestine and the liver, and (ii) the subsequent metabolism of lipids and FA by tissues. In preruminant calves, high-fat feed stimulates the secretion of triacylglycerols (TG)-rich lipoproteins (chylomicrons, very-low density lipoproteins (VLDL)). Diets rich in polyunsaturated FA (PUFA) stimulate the production of chylomicrons by the intestine (at peak lipid absorption) and of high density lipoproteins by the liver, leading to high blood concentrations of cholesterol. High levels of non-esterified FA (NEFA) uptake by the liver in high-yielding dairy cows in early lactation leads to TG infiltration of the hepatocytes (fatty liver). This is due to the low chronic capacity of the liver to synthesise and secrete VLDL particles. This abnormality in hepatic FA metabolism involves defects in apolipoprotein B synthesis and low availability of apolipoproteins and lipids for VLDL packaging. Fatty liver in calves is also caused by milk containing either soybean oil (rich in n-6 PUFA), or coconut oil (rich in C12:0 and C14:0). The ability of muscle tissue to use FA as an energy source depends on its mitochondrial content and, hence, on many physiological factors. The

  19. Micro-Macro Scale Mixing Interactions by Intestinal Villi Enhance Absorption: a 3D Lattice-Boltzmann Model

    NASA Astrophysics Data System (ADS)

    Wang, Yanxing; Brasseur, James; Banco, Gino

    2010-11-01

    Muscle-induced villi motions may create a micro-scale flow that couples with a lumen-scale macro flow to enhance nutrient transport and absorption in the intestine. Using a 3D multiscale lattice Boltzmann model of a lid-driven cavity flow with microscale 3-D leaf and finger-like villi in pendular motion at the lower surface, we analyze the coupling between micro and macro-scale nutrient mixing and absorption at the villi surfaces. RESULTS: The villi motions enhance absorption by creating a micro-mixing layer (MML) that pumps low concentration fluid from between villi groups and attracts fluid with high concentration from the macro flow. The MML couples with the macro flow via a diffusion layer. Leaf-like villi create the strongest MML and, consequently, the highest absorption rates. The finger-like villi create a weaker MML due to the existence of flow between villi. The strength of the MML and nutrient absorption increases with villus frequency. The absorption rate also increases with villus length; however the simulations predict an optimal length close to the physiological length of villi in humans. The complex flow structure will be discussed. We conclude that the interaction between micro-scale villi-induced fluid motions and macro-scale motility-induced flow may play a significant role in intestinal absorption. Supported by NSF Grant CTS-056215.

  20. Influence of prolactin and calcium gluconate concentration on permeation and intestinal absorption of Ca(II) ions.

    PubMed

    Ryszka, Florian; Klimas, Rimantas; Dolinska, Barbara; Lopata, Katarzyna

    2012-08-01

    The in vitro permeation and absorption of calcium ions across the small intestine were measured at different concentrations of calcium gluconate solutions (1.0, 10.0 and 20.0 mM) with or without prolactin. The calcium ions permeated through the small intestine from a donor environment to an acceptor environment that mimicked the conditions in the stomach to ileum segment of the digestive tract. The permeation and absorption of calcium were directly dependent on the calcium concentration of the solutions. At 10 and 20 mM permeation was significantly higher than that at 1.0 mM (p < 0.05). In the presence of prolactin both permeation and absorption increase considerably. At the lowest concentration (1.0 mM) simulating calcium deficiency, there was compensation by the small intestine, suggesting that such deficiency stimulates its mobilization from intestinal tissue. Prolactin enhances the calcium mobilization process even at sufficient calcium intakes. It is suggested that prolactin takes part in regulation of calcium homeostasis in the organism. PMID:22702896

  1. Bioavailability of dietary (poly)phenols: a study with ileostomists to discriminate between absorption in small and large intestine.

    PubMed

    Borges, Gina; Lean, Michael E J; Roberts, Susan A; Crozier, Alan

    2013-04-30

    A feeding study was carried out in which six healthy ileostomists ingested a juice drink containing a diversity of dietary (poly)phenols derived from green tea, apples, grapes and citrus fruit. Ileal fluid and urine collected at intervals over the ensuing 24 h period were then analysed by HPLC-MS. Urinary excretions were compared with results obtained in an earlier study in which the juice drink was ingested by ten healthy control subjects with an intact colon. Some polyphenol components, such as (epi)catechins and (epi)gallocatechin(s), were excreted in urine in similar amounts in ileostomists and subjects with an intact colon, demonstrating that absorption took place principally in the small intestine. In the urine of ileostomists, there were reduced levels of other constituents, including hesperetin-7-O-rutinoside, 5-O-caffeoylquinic acid and dihydrochalcones, indicating their absorption in both the small and large intestine. Ileal fluid analysis revealed that even when absorption occurred in the small intestine, in subjects with a functioning colon a substantial proportion of the ingested components still pass from the small into the large intestine, where they may be either absorbed before or after catabolism by colonic bacteria.

  2. The effect of catecholamines on intestinal glucose and oxygen uptake in the dog.

    PubMed Central

    Grayson, J; Oyebola, D D

    1983-01-01

    Using the anaesthetized dog, continuous recording was made of the oxygen and glucose contents of the artery and the vein draining the upper jejunum. Flow was also measured and results expressed as differences in oxygen and glucose between the aorta and the jejunal vein (a-v), also as oxygen consumption and glucose uptake. Resting glucose uptake was greater than could be accounted for on the basis of oxidation. When adrenaline (1 microgram/kg. min) or noradrenaline (2 micrograms/kg. min) was infused intravenously, oxygen uptake rose by about 50% whereas glucose uptake rose by 300-500%; moreover, the rise in glucose uptake was apparent before the rise in oxygen uptake. The beta-blocking agent, propranolol (0 X 5 mg/kg. min) had no effect on oxygen uptake but caused a three-fold rise in glucose uptake. Subsequently infusion of adrenaline had no effect on oxygen uptake and no effect on glucose uptake. However, on stopping the infusion there was a marked drop in glucose uptake, which was not maintained. It is suggested that the effects of catecholamines may be due to altered arterial blood glucose levels and that the jejunum may play a role in glucose homeostasis which requires the action of beta receptors. PMID:6644618

  3. Intestinal water absorption through aquaporin 1 expressed in the apical membrane of mucosal epithelial cells in seawater-adapted Japanese eel.

    PubMed

    Aoki, Mayumi; Kaneko, Toyoji; Katoh, Fumi; Hasegawa, Sanae; Tsutsui, Naoaki; Aida, Katsumi

    2003-10-01

    To elucidate the mechanisms associated with water absorption in the intestine, we compared drinking and intestinal water absorption in freshwater- and seawater-adapted Japanese eels, and investigated a possible involvement of aquaporin (AQP) in the absorption of water in the intestine. Seawater eels ingested more water than freshwater eels, the drinking rate being 0.02 ml kg(-1) h(-1) in fresh water and 0.82 ml kg(-1) h(-1) in sea water. In intestinal sacs prepared from freshwater and seawater eels, water absorption increased in time- and hydrostatic pressure-dependent manners. The water absorption rates were greater in seawater sacs than in freshwater sacs, and also greater in the posterior intestine than in the anterior. In view of the enhanced water permeability in the intestine of seawater eel, we cloned two cDNAs encoding AQP from the seawater eel intestine, and identified two eel homologues (S-AQP and L-AQP) of mammalian AQP1. S-AQP and L-AQP possessed the same amino acid sequence, except that one amino acid was lacking in S-AQP and two amino acids were substituted. Eel AQP1 was expressed predominantly in the intestine, and the expression levels were higher in seawater eel than in freshwater eel. Immunocytochemical studies revealed intense AQP1 immunoreaction in the apical surface of columnar epithelial cells in seawater eel, in which the immunoreaction was stronger in the posterior intestine than in the anterior. In contrast, the immunoreaction was faint in the freshwater eel intestine. Preferential localization of AQP1 in the apical membrane of epithelial cells in the posterior intestine of seawater eel indicates that this region of the intestine is responsible for water absorption, and that AQP1 may act as a water entry site in the epithelial cells.

  4. Water absorption and bicarbonate secretion in the intestine of the sea bream are regulated by transmembrane and soluble adenylyl cyclase stimulation.

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Power, Deborah M; Canário, Adelino V M; Fuentes, Juan

    2012-12-01

    In the marine fish intestine luminal, HCO₃⁻ can remove divalent ions (calcium and magnesium) by precipitation in the form of carbonate aggregates. The process of epithelial HCO₃⁻ secretion is under endocrine control, therefore, in this study we aimed to characterize the involvement of transmembrane (tmACs) and soluble (sACs) adenylyl cyclases on the regulation of bicarbonate secretion (BCS) and water absorption in the intestine of the sea bream (Sparus aurata). We observed that all sections of sea bream intestine are able to secrete bicarbonate as measured by pH-Stat in Ussing chambers. In addition, gut sac preparations reveal net water absorption in all segments of the intestine, with significantly higher absorption rates in the anterior intestine that in the rectum. BCS and water absorption are positively correlated in all regions of the sea bream intestinal tract. Furthermore, stimulation of tmACs (10 μM FK + 500 μM IBMX) causes a significant decrease in BCS, bulk water absorption and short circuit current (Isc) in a region dependent manner. In turn, stimulation of sACs with elevated HCO₃⁻ results in a significant increase in BCS, and bulk water absorption in the anterior intestine, an action completely reversed by the sAC inhibitor KH7 (200 μM). Overall, the results reveal a functional relationship between BCS and water absorption in marine fish intestine and modulation by tmACs and sAC. In light of the present observations, it is hypothesized that the endocrine effects on intestinal BCS and water absorption mediated by tmACs are locally and reciprocally modulated by the action of sACs in the fish enterocyte, thus fine-tuning the process of carbonate aggregate production in the intestinal lumen. PMID:22752677

  5. Water absorption and bicarbonate secretion in the intestine of the sea bream are regulated by transmembrane and soluble adenylyl cyclase stimulation.

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Power, Deborah M; Canário, Adelino V M; Fuentes, Juan

    2012-12-01

    In the marine fish intestine luminal, HCO₃⁻ can remove divalent ions (calcium and magnesium) by precipitation in the form of carbonate aggregates. The process of epithelial HCO₃⁻ secretion is under endocrine control, therefore, in this study we aimed to characterize the involvement of transmembrane (tmACs) and soluble (sACs) adenylyl cyclases on the regulation of bicarbonate secretion (BCS) and water absorption in the intestine of the sea bream (Sparus aurata). We observed that all sections of sea bream intestine are able to secrete bicarbonate as measured by pH-Stat in Ussing chambers. In addition, gut sac preparations reveal net water absorption in all segments of the intestine, with significantly higher absorption rates in the anterior intestine that in the rectum. BCS and water absorption are positively correlated in all regions of the sea bream intestinal tract. Furthermore, stimulation of tmACs (10 μM FK + 500 μM IBMX) causes a significant decrease in BCS, bulk water absorption and short circuit current (Isc) in a region dependent manner. In turn, stimulation of sACs with elevated HCO₃⁻ results in a significant increase in BCS, and bulk water absorption in the anterior intestine, an action completely reversed by the sAC inhibitor KH7 (200 μM). Overall, the results reveal a functional relationship between BCS and water absorption in marine fish intestine and modulation by tmACs and sAC. In light of the present observations, it is hypothesized that the endocrine effects on intestinal BCS and water absorption mediated by tmACs are locally and reciprocally modulated by the action of sACs in the fish enterocyte, thus fine-tuning the process of carbonate aggregate production in the intestinal lumen.

  6. A comparison of pharmacokinetic methods for in vivo studies of nonmediated glucose absorption.

    PubMed

    Napier, Kathryn R; McWhorter, Todd J; Fleming, Patricia A

    2012-01-01

    Two pharmacokinetic methods are used primarily to assess systematic bioavailability of orally dosed water-soluble compounds in vivo, but there have been no direct comparisons of the estimates obtained. The "area under the curve" (AUC) method employs a single oral dose of probe compound(s) followed by multiple blood sampling to obtain plasma concentration time curves. Separate injection of probe(s) followed by multiple blood sampling is used to calculate fractional elimination rate (K(el)) and distribution pool space (S). The "steady state feeding" method relies on ad lib. feeding of a marked diet, with a single blood sample taken to measure steady state feeding concentration of probe(s); K(el) is estimated from the decline in probe concentration in excreta after injection, with a single blood sample taken to estimate S. We compared these methods directly in the Australian red wattlebird (Anthochaera carnunculata), measuring absorption of (3)H-L-glucose. The K(el) values estimated using the steady state feeding protocol were significantly higher, and estimates of S and bioavailability consequently lower, compared with the AUC protocol. The AUC method relies on fewer assumptions and allows simultaneous comparisons of absorption by mediated and nonmediated (i.e., paracellular) mechanisms but cannot be easily applied to freely feeding animals. The steady state feeding method allows work with smaller species and exploration of the effects of feeding on nutrient uptake but requires careful attention to the validity of assumptions that increase error in the calculations.

  7. Increased systemic exposure to rhizoma coptidis alkaloids in lipopolysaccharide-pretreated rats attributable to enhanced intestinal absorption.

    PubMed

    Ma, Bing-Liang; Yao, Meng-Kan; Zhong, Jie; Ma, Yue-Ming; Gao, Cheng-Lu; Wu, Jia-Sheng; Qiu, Fu-Rong; Wang, Chang-Hong; Wang, Xin-Hong

    2012-02-01

    Rhizoma coptidis is a rhizome commonly used in traditional Chinese medicine. After oral administration of rhizoma coptidis extract, the plasma concentrations of its effective alkaloid constituents are so low that their systemic therapeutic actions cannot be explained. This study aimed to investigate the influence of lipopolysaccharide (LPS) on the pharmacokinetics of the rhizoma coptidis alkaloids. Pharmacokinetic experiments were performed with rats; both in vitro absorption and efflux experiments were carried out with everted rat gut sacs, whereas in vitro metabolism experiments were conducted with rat liver microsomes and intestinal S9 fractions. Mucosal changes were evaluated with light microscopy and transmission electron microscopy. The results showed that, in rat plasma, LPS pretreatment increased systemic alkaloid exposure. LPS pretreatment increased the in vitro absorption of the alkaloids and decreased their efflux. The efflux of vinblastine and rhodamine 123, P-glycoprotein substrates, also was decreased. The absorption of fluorescein isothiocyanate-labeled dextran (average molecular mass, 4 kDa), a gut paracellular permeability probe, was not influenced. Obvious damage was observed in the mucosa, but the tight junctions between epithelial cells remained intact. Intestinal, rather than hepatic, alkaloid metabolism was decreased. These findings indicated that LPS pretreatment increased systemic exposure to the alkaloids through enhancement of their absorption, which was related to decreased intestinal efflux and metabolism. The results add to the understanding of why rhizoma coptidis is active despite the low plasma concentrations of the rhizoma coptidis alkaloids measured in normal subjects and experimental animals.

  8. Influence of class B scavenger receptors on cholesterol flux across the brush border membrane and intestinal absorption.

    PubMed

    Nguyen, David V; Drover, Victor A; Knopfel, Martin; Dhanasekaran, Padmaja; Hauser, Helmut; Phillips, Michael C

    2009-11-01

    To learn more about how the step of cholesterol uptake into the brush border membrane (BBM) of enterocytes influences overall cholesterol absorption, we measured cholesterol absorption 4 and 24 h after administration of an intragastric bolus of radioactive cholesterol in mice with scavenger receptor class B, type 1 (SR-BI) and/or cluster determinant 36 (CD36) deleted. The cholesterol absorption efficiency is unaltered by deletion of either one or both of the receptors. In vitro determinations of the cholesterol uptake specific activity of the BBM from the mice reveal that the scavenger receptors facilitate cholesterol uptake into the proximal BBM. It follows that cholesterol uptake into the BBM is not normally rate-limiting for the cholesterol absorption process in vivo; a subsequent step, such as NPC1L1-mediated transfer from the BBM into the interior of the enterocyte, is rate-limiting. The absorption of dietary cholesterol after 4 h in mice lacking SR-BI and/or CD36 and fed a high-fat/high-cholesterol diet is delayed to more distal regions of the small intestine. This effect probably arises because ATP binding cassette half transporters G5 and G8-mediated back flux of cholesterol from the BBM to the lumen of the small intestine limits absorption and causes the local cholesterol uptake facilitated by SR-BI and CD36 to become rate-limiting under this dietary condition. PMID:19454765

  9. Mass balance approaches for estimating the intestinal absorption and metabolism of peptides and analogues: theoretical development and applications

    NASA Technical Reports Server (NTRS)

    Sinko, P. J.; Leesman, G. D.; Amidon, G. L.

    1993-01-01

    A theoretical analysis for estimating the extent of intestinal peptide and peptide analogue absorption was developed on the basis of a mass balance approach that incorporates convection, permeability, and reaction. The macroscopic mass balance analysis (MMBA) was extended to include chemical and enzymatic degradation. A microscopic mass balance analysis, a numerical approach, was also developed and the results compared to the MMBA. The mass balance equations for the fraction of a drug absorbed and reacted in the tube were derived from the general steady state mass balance in a tube: [formula: see text] where M is mass, z is the length of the tube, R is the tube radius, Pw is the intestinal wall permeability, kr is the reaction rate constant, C is the concentration of drug in the volume element over which the mass balance is taken, VL is the volume of the tube, and vz is the axial velocity of drug. The theory was first applied to the oral absorption of two tripeptide analogues, cefaclor (CCL) and cefatrizine (CZN), which degrade and dimerize in the intestine. Simulations using the mass balance equations, the experimental absorption parameters, and the literature stability rate constants yielded a mean estimated extent of CCL (250-mg dose) and CZN (1000-mg dose) absorption of 89 and 51%, respectively, which was similar to the mean extent of absorption reported in humans (90 and 50%). It was proposed previously that 15% of the CCL dose spontaneously degraded systematically; however, our simulations suggest that significant CCL degradation occurs (8 to 17%) presystemically in the intestinal lumen.(ABSTRACT TRUNCATED AT 250 WORDS).

  10. Effect of medium-chain glycerides (MGK) on the intestinal absorption and the hepatobiliary transport of bromthymol blue.

    PubMed

    Higaki, K; Kishimoto, I; Komatsu, H; Hashida, M; Sezaki, H

    1986-06-01

    The effect of medium chain glyceride (MGK) emulsion on the intestinal absorption and the biliary excretion of bromthymol blue (BTB) was investigated in rats. Extensive tissue accumulation of BTB was reduced when BTB was administered with MGK emulsion formulation. HCO-100, an emulsifier, was also important for the decrease in the tissue accumulation of BTB. The ratios of absorption percent to tissue accumulation percent and to free fraction, not contained in the droplet of emulsion, in MGK emulsion were much greater than that of the control. Pretreatment with BTB-free emulsion reduced BTB absorption under the control, although tissue accumulation was not affected. The absorption appeared to decrease with increase in the time of pretreatment. The effect of leaving treatment after pretreatment on the absorption of BTB was also investigated. With the increase in leaving time after pretreatment, reduced absorption tended to resume to the level of control. The change in monocaprylate content from 54 to 60% in MGK made a difference in BTB absorption and it was suggested that monocaprylate content in MGK was one of the significant factors of MGK emulsion on drug absorption. Bile recovery study was simultaneously carried out with an in situ recirculation experiment. The recovery of BTB into bile tended to decrease. The ratio of recovery percent of BTB into bile to the absorption percent of BTB also decreased extensively, which is possibly another effect of MGK on drug disposition. PMID:3761141

  11. Bioactive Dietary Polyphenols Inhibit Heme Iron Absorption in A Dose-Dependent Manner in Human Intestinal Caco-2 cells

    PubMed Central

    Ma, Qianyi; Kim, Eun-Young; Lindsay, Elizabeth Ann; Han, Okhee

    2011-01-01

    Although heme iron is an important form of dietary iron, its intestinal absorption mechanism remains elusive. Our previous work revealed that (−)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) markedly inhibited intestinal heme iron absorption by reducing the basolateral iron export in Caco-2 cells. The aims of this study were to examine whether small amounts of EGCG, GSE and green tea extract (GT) could inhibit heme iron absorption, and to test whether the inhibitory action of polyphenols could be offset by ascorbic acid. A heme-55Fe absorption study was conducted by adding various concentrations of EGCG, GSE and GT to Caco-2 cells in the absence and presence of ascorbic acid. Polyphenolic compounds significantly inhibited heme-55Fe absorption in a dose-dependent manner. The addition of ascorbic acid did not modulate the inhibitory effect of dietary polyphenols on heme iron absorption when the cells were treated with polyphenols at a concentration of 46 mg/L. However, ascorbic acid was able to offset or reverse the inhibitory effects of polyphenolic compounds when lower concentrations of polyphenols were added (≤ 4.6 mg/L). Ascorbic acid modulated the heme iron absorption without changing the apical heme uptake, the expression of the proteins involved in heme metabolism and basolateral iron transport, and heme oxygenase activity, indicating that ascorbic acid may enhance heme iron absorption by modulating the intracellular distribution of 55Fe. These results imply that the regular consumption of dietary ascorbic acid can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption but cannot counteract the inhibitory actions of high concentrations of polyphenols. PMID:22417433

  12. Label-free assay for the detection of glucose mediated by the effects of narrowband absorption on quantum dot photoluminescence

    NASA Astrophysics Data System (ADS)

    Khan, Saara A.; Smith, Gennifer T.; Ellerbee, Audrey K.

    2014-03-01

    We present a novel strategy for label-free detection of glucose based on CdSe/ZnS core/shell quantum dots (QDs). We exploit the concentration-dependent, narrowband absorption of the hexokinase-glucose 6-phosphate dehydrogenase enzymatic assay to selectively filter a 365-nm excitation source, leading to a proportional decrease in the photoluminescence intensity of the QDs. The visible wavelength emission of the QDs enables quantitative readout using standard visible detectors (e.g., CCD). Experimental results show highly linear QD photoluminescence over the clinically relevant glucose concentration range of 1-25mM, in excellent agreement with detection methods demonstrated by others. The method has a demonstrated limit of detection of 3.5μM, also on par with the best proposed methods. A significant advantage of our strategy is the complete elimination of QDs as a consumable. In contrast with other methods of QD-based measurement of glucose, our system does not require the glucose solution to be mixed with the QDs, thereby decreasing its overall cost and making it an ideal strategy for point-of-care detection of glucose in low-resource areas. Furthermore, readout can be accomplished with low-cost, portable detectors such as cellular phones, eliminating the need for expensive and bulky spectrophotometers to output quantitative information. The general strategy we present is useful for other biosensing applications involving chemistries with unique absorption peaks falling within the excitation band of available QDs.

  13. Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

    PubMed

    Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

    2015-12-01

    This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the P(app) and K(a) of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions.

  14. Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.

    PubMed Central

    Levens, N R; Peach, M J; Carey, R M

    1981-01-01

    The purpose of this study was to determine the locus of interaction of angiotensin peptides with the sympathetic nervous system leading to alterations in jejunal sodium and water transport. At low physiological doses, angiotensin II (AII) stimulates jejunal sodium and water absorption, while at high doses peptide inhibits absorption and/or stimulates secretion. Both the stimulation of jejunal transport and the inhibition of absorption were expressed in adrenalectomized rats. However, the stimulation of jejunal water absorption was abolished and a potentiated inhibition of transport was expressed in peripherally sympathectomized rats (intact adrenal medulla) and in normal rats after administration of guanethadine, phentolamine, and prazosin. The angiotensin analog (Sar1 Leu8)-AII has low efficacy and is a potent competitive antagonist of the parent peptide in pressor and myotropic systems, but is a full agonist with even greater potency than AII in stimulating jejunal transport. The increased water transport in response to (Sar1 Leu8)-AII is not secondary to enhanced renal renin release, as the analog also stimulated jejunal transport in the presence of captopril and after bilateral nephrectomy. The stimulation of absorption in response to (Sar1 Leu8)-AII alone or together with AII was abolished by phentolamine. These data demonstrate that AII-increased intestinal absorption is secondary to the release of norepinephrine from nerve endings in the jejunum and that AII inhibition of absorption is not mediated by the sympathetic nervous system. The analog (Sar1 Leu8)-AII is a full agonist in the stimulation of jejunal transport (increased norepinephrine release), but antagonizes the inhibitory response to high doses of AII. Angiotensin peptides are potent modulators of intestinal sodium and water absorption. PMID:7204574

  15. PTHrP regulates water absorption and aquaporin expression in the intestine of the marine sea bream (Sparus aurata, L.).

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Canário, Adelino V M; Power, Deborah M; Fuentes, Juan

    2015-03-01

    Water ingestion by drinking is fundamental for ion homeostasis in marine fish. However, the fluid ingested requires processing to allow net water absorption in the intestine. The formation of luminal carbonate aggregates impacts on calcium homeostasis and requires epithelial HCO3(-) secretion to enable water absorption. In light of its endocrine importance in calcium handling and the indication of involvement in HCO3(-) secretion the present study was designed to expose the role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion, water absorption and the regulation of aqp1 gene expression in the anterior intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34) was added to anterior intestine of the sea bream mounted in Ussing chambers. The effect achieved a maximum inhibition of 60% of basal secretion rates, showing a threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) or the phospholipase C inhibitor (U73122, 10 μmol l(-1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in both cases. In parallel, bulk water absorption measured in intestinal sacs was sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect of 60-65% inhibition from basal rates and shows threshold significant effects at hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was completely abolished in the presence of the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 μmol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP acts as a key

  16. PTHrP regulates water absorption and aquaporin expression in the intestine of the marine sea bream (Sparus aurata, L.).

    PubMed

    Carvalho, Edison S M; Gregório, Sílvia F; Canário, Adelino V M; Power, Deborah M; Fuentes, Juan

    2015-03-01

    Water ingestion by drinking is fundamental for ion homeostasis in marine fish. However, the fluid ingested requires processing to allow net water absorption in the intestine. The formation of luminal carbonate aggregates impacts on calcium homeostasis and requires epithelial HCO3(-) secretion to enable water absorption. In light of its endocrine importance in calcium handling and the indication of involvement in HCO3(-) secretion the present study was designed to expose the role of the parathyroid hormone-related protein (PTHrP) in HCO3(-) secretion, water absorption and the regulation of aqp1 gene expression in the anterior intestine of the sea bream. HCO3(-) secretion rapidly decreased when PTHrP(1-34) was added to anterior intestine of the sea bream mounted in Ussing chambers. The effect achieved a maximum inhibition of 60% of basal secretion rates, showing a threshold effective dose of 0.1 ng ml(-1) compatible with reported plasma values of PTHrP. When applied in combination with the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) or the phospholipase C inhibitor (U73122, 10 μmol l(-1)) the effect of PTHrP(1-34) on HCO3(-) secretion was reduced by about 50% in both cases. In parallel, bulk water absorption measured in intestinal sacs was sensitive to inhibition by PTHrP. The inhibitory action conforms to a typical dose-response curve in the range of 0.1-1000 ng ml(-1), achieves a maximal effect of 60-65% inhibition from basal rates and shows threshold significant effects at hormone levels of 0.1 ng ml(-1). The action of PTHrP in water absorption was completely abolished in the presence of the adenylate cyclase inhibitor (SQ 22.536, 100 μmol l(-1)) and was insensitive to the phospholipase C inhibitor (U73122, 10 μmol l(-1)). In vivo injections of PTHrP(1-34) or the PTH/PTHrP receptor antagonist PTHrP(7-34) evoked respectively, a significant decrease or increase of aqp1ab, but not aqp1a. Overall the present results suggest that PTHrP acts as a key

  17. Role of 1,25-dihydroxyvitamin D3 on intestinal phosphate absorption in rats with a normal vitamin D supply.

    PubMed

    Rizzoli, R; Fleisch, H; Bonjour, J P

    1977-09-01

    In vitamin D-deficient rats, impaired intestinal phosphorus (P) absorption can be corrected by 1,25-dihydroxyvitamin D(3)[1,25-(OH)(2)D(3)]. In the present study, it was investigated whether changes in 1,25-(OH)(2)D(3) production can influence intestinal P transport also in animals with a normal supply of vitamin D. The intestinal P absorption was evaluated in rats using both the in situ duodenal loop technique and the determination of the overall gastrointestinal absorption under three conditions known to influence the production of 1,25-(OH)(2)D(3): (a) variation in dietary P, (b) thyroparathyroidectomy (TPTX) with or without administration of parathyroid hormone (PTH), and (c) treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). In all circumstances changes in duodenal absorption paralleled the changes in the overall fractional absorption. (a) Lowering dietary P stimulated P absorption. (b) TPTX decreased P absorption. This effect was corrected either by the administration of PTH or by the administration of 1,25-(OH)(2)D(3). (c) EHDP, when given at a dose known to inhibit 1,25-(OH)(2)D(3) formation, decreased the duodenal P absorption in both intact and TPTX animals. This effect was corrected by 1,25-(OH)(2)D(3). In the TPTX-EHDP-treated animals, the administration of PTH did not rectify the low duodenal P absorption. These results support the thesis that, in rats with normal vitamin D supply, variations in the endogenous production of 1,25-(OH)(2)D(3) change the rate of P absorption. However, these changes are in such magnitude that they are of relatively small importance when compared to the effect of variation in the dietary intake of P. These results also strongly suggest that the action of PTH on duodenal P transport is mediated by its effect on 1,25-(OH)(2)D(3) production, inasmuch as the effect of the hormone is abolished after blocking the renal 1-hydroxylation with EHDP.

  18. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells. PMID:25573173

  19. Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function.

    PubMed

    Grant, Christa N; Mojica, Salvador Garcia; Sala, Frederic G; Hill, J Ryan; Levin, Daniel E; Speer, Allison L; Barthel, Erik R; Shimada, Hiroyuki; Zachos, Nicholas C; Grikscheit, Tracy C

    2015-04-15

    Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells.

  20. The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity

    PubMed Central

    Tang, Lieqi; Cheng, Catherine Y.; Sun, Xiangrong; Pedicone, Alexandra J.; Mohamadzadeh, Mansour; Cheng, Sam X.

    2016-01-01

    Different from other epithelia, the intestinal epithelium has the complex task of providing a barrier impeding the entry of toxins, food antigens, and microbes, while at the same time allowing for the transfer of nutrients, electrolytes, water, and microbial metabolites. These molecules/organisms are transported either transcellularly, crossing the apical and basolateral membranes of enterocytes, or paracellularly, passing through the space between enterocytes. Accordingly, the intestinal epithelium can affect energy metabolism, fluid balance, as well as immune response and tolerance. To help accomplish these complex tasks, the intestinal epithelium has evolved many sensing receptor mechanisms. Yet, their roles and functions are only now beginning to be elucidated. This article explores one such sensing receptor mechanism, carried out by the extracellular calcium-sensing receptor (CaSR). In addition to its established function as a nutrient sensor, coordinating food digestion, nutrient absorption, and regulating energy metabolism, we present evidence for the emerging role of CaSR in the control of intestinal fluid homeostasis and immune balance. An additional role in the modulation of the enteric nerve activity and motility is also discussed. Clearly, CaSR has profound effects on many aspects of intestinal function. Nevertheless, more work is needed to fully understand all functions of CaSR in the intestine, including detailed mechanisms of action and specific pathways involved. Considering the essential roles CaSR plays in gastrointestinal physiology and immunology, research may lead to a translational opportunity for the development of novel therapies that are based on CaSR's unique property of using simple nutrients such as calcium, polyamines, and certain amino acids/oligopeptides as activators. It is possible that, through targeting of intestinal CaSR with a combination of specific nutrients, oral solutions that are both inexpensive and practical may be

  1. Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2.

    PubMed

    Zhang, Shihai; Yang, Qing; Ren, Man; Qiao, Shiyan; He, Pingli; Li, Defa; Zeng, Xiangfang

    2016-08-01

    Knowledge of regulation of glucose transport contributes to our understanding of whole-body glucose homoeostasis and human metabolic diseases. Isoleucine has been reported to participate in regulation of glucose levels in many studies; therefore, this study was designed to examine the effect of isoleucine on intestinal and muscular GLUT expressions. In an animal experiment, muscular GLUT and intestinal GLUT were determined in weaning pigs fed control or isoleucine-supplemented diets. Supplementation of isoleucine in the diet significantly increased piglet average daily gain, enhanced GLUT1 expression in red muscle and GLUT4 expression in red muscle, white muscle and intermediate muscle (P<0·05). In additional, expressions of Na+/glucose co-transporter 1 and GLUT2 were up-regulated in the small intestine when pigs were fed isoleucine-supplemented diets (P<0·05). C2C12 cells were used to examine the expressions of muscular GLUT and glucose uptake in vitro. In C2C12 cells supplemented with isoleucine in the medium, cellular 2-deoxyglucose uptake was increased (P<0·05) through enhancement of the expressions of GLUT4 and GLUT1 (P<0·05). The effect of isoleucine was greater than that of leucine on glucose uptake (P<0·05). Compared with newborn piglets, 35-d-old piglets have comparatively higher GLUT4, GLUT2 and GLUT5 expressions. The results of this study demonstrated that isoleucine supplementation enhanced the intestinal and muscular GLUT expressions, which have important implications that suggest that isoleucine could potentially increase muscle growth and intestinal development by enhancing local glucose uptake in animals and human beings. PMID:27464458

  2. In vitro effect of fenugreek extracts on intestinal sodium-dependent glucose uptake and hepatic glycogen phosphorylase A.

    PubMed

    Al-Habori, M; Raman, A; Lawrence, M J; Skett, P

    2001-01-01

    Fenugreek (Trigonella foenum-graecum L. seed) is a food with traditional medicinal use in diabetes. Beneficial effects have been demonstrated in diabetic animals and both insulin-dependent and non-insulin-dependent diabetic subjects. Effects of a lipid extract A, crude ethanolic extract B, further sub-fractions of B (saponin-free C, saponin D and sapogenin E) and a gum fibre fraction F on intestinal sodium-dependent glucose uptake were investigated in vitro using rabbit intestinal brush border membrane vesicles. All fractions except A inhibited glucose-uptake at 0.33 and/or 3.3 mg/mL (p < 0.001). Greatest inhibition was observed with fractions D and E. Diosgenin and trigonelline (compounds reported in fenugreek) also inhibited glucose-uptake (IC50 values approximately 3 mg/ml, equivalent to 8 mM and 19 mM respectively) but did not account for the activity of the crude extracts. Fenugreek extracts had no effect on basal levels of glycogen phosphorylase a (HGPa) activity in rat hepatocyte suspensions. However fractions C and E caused a marginal but statistically significant inhibition (18.9 and 15.1% respectively, p < 0.05) of glucagon induction of this enzyme suggesting a glucagon-antagonist effect. Diosgenin (1.65 mg/ml; 4 mM) inhibited glucagon-induced HGPa activity by 20% (p < 0.05), and was more effective than trigonelline (non significant inhibition of 9.4% at 1.65 mg/ml, 10 mM). PMID:12369721

  3. Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity

    PubMed Central

    Zhou, Wei; Zhu, Xuan Xuan; Yin, Ai Ling; Cai, Bao Chang; Wang, Hai Dan; Di, Liuqing; Shan, Jin Jun

    2014-01-01

    Background: Forsythoside A (FTA), one of the main active ingredients in Shuang–Huang–Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. Materials and Methods: In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. Results: The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Conclusion: Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL. PMID:24695554

  4. Description and validation of an in situ autoperfusion method to determine nutrient absorption and metabolism in bovine small intestine.

    PubMed

    Murray, R A; Nocek, J E; Schwab, C G; Hylton, W E; Bozak, C K

    1987-09-01

    Holstein bull calves, 8 to 12 wk of age, were anesthetized with halothane gas. An approximate 20-cm section of small intestine, 60 to 90 cm proximal to the ileocecal junction was clamped to isolate blood circulation to a single set of arcuate vessels and to form an intestinal segment fitted for infusion and drainage. The vein was catheterized to allow total venous collection. Donor blood was transfused via jugular vein to replace venous drainage. This technique was evaluated in four calves by exposing the lumen to eight replications (12 or 20 min incubation, 30-min wash with 39 C saline) of 16 mM L-Met (14C-labeled). Time course appearance of Met in venous blood indicated similar rates and patterns of absorption for individual calves. There were no clinically significant alterations in jugular blood chemistry profiles across replications. Four calves were used to evaluate the effect of three isotonic perfusion media (saline, Krebs-Ringer bicarbonate and M-199 tissue culture media) on Lys and Met absorption. Venous flow rates and absorption of Lys were faster with Krebs buffer than with other media. Perfusate medium did not influence venous flow rates or absorption of Met. Effect of restricting venous flow on absorption of Lys and Met was evaluated in two calves. Flow was alternately controlled (6.5 ml/min) or allowed to flow freely (mean = 12.2 ml/min). Restricting flow decreased steady-state absorption. Light and scanning microscopy indicated maintenance of mucosal tissue integrity throughout 8 h of anesthesia. Results demonstrate validity of the in situ technique to study nutrient absorption in the young bovine.

  5. Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches.

    PubMed

    Basant, Nikita; Gupta, Shikha; Singh, Kunwar P

    2016-04-01

    Human intestinal absorption (HIA) of the drugs administered through the oral route constitutes an important criterion for the candidate molecules. The computational approach for predicting the HIA of molecules may potentiate the screening of new drugs. In this study, ensemble learning (EL) based qualitative and quantitative structure-activity relationship (SAR) models (gradient boosted tree, GBT and bagged decision tree, BDT) have been established for the binary classification and HIA prediction of the chemicals, using the selected molecular descriptors. The structural diversity of the chemicals and the nonlinear structure in the considered data were tested by the similarity index and Brock-Dechert-Scheinkman statistics. The external predictive power of the developed SAR models was evaluated through the internal and external validation procedures recommended in the literature. All the statistical criteria parameters derived for the performance of the constructed SAR models were above their respective thresholds suggesting for their robustness for future applications. In complete data, the qualitative SAR models rendered classification accuracy of >99%, while the quantitative SAR models yielded correlation (R(2)) of >0.91 between the measured and predicted HIA values. The performances of the EL-based SAR models were also compared with the linear models (linear discriminant analysis, LDA and multiple linear regression, MLR). The GBT and BDT SAR models performed better than the LDA and MLR methods. A comparison of our models with the previously reported QSARs for HIA prediction suggested for their better performance. The results suggest for the appropriateness of the developed SAR models to reliably predict the HIA of structurally diverse chemicals and can serve as useful tools for the initial screening of the molecules in the drug development process.

  6. Intestinal transport of hexoses in the rat following chronic heat exposure

    NASA Technical Reports Server (NTRS)

    Carpenter, M.; Musacchia, X. J.

    1979-01-01

    The study examines intestinal transport of sugars (D-glucose and D-galactose) in vitro and assesses organ maintenance in chronically heat-exposed rats. The results suggest that the response of intestinal absorption to heat exposure in the rat involves changes in intestinal weight and in glucose utilization. Despite the reduction in total intestinal weight, the ability of intestinal tissue to transport hexose per unit weight remains stable. Differences in intestinal weight and glucose utilization between pair-fed and heat-exposed animals suggest that the intestinal response to chronic heat exposure is not solely a function of the amount of food consumed. Alterations of hexose transport appear to be related to altered glucose metabolism and not altered transport capacity.

  7. The rule of unity for human intestinal absorption 2: application to pharmaceutical drugs that are marketed as salts.

    PubMed

    Patel, Raj B; Admire, Brittany; Yalkowsky, Samuel H

    2015-01-01

    The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA <0.5) and those that are well absorbed (FA ≥ 0.5). Inspection of the data as well as a receiver operative characteristic (ROC) plot shows that a single critical MAP value can be used for predicting efficient human absorption of drugs. This forms the basis of a simple rule of unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

  8. Identification of intestinal bicarbonate transporters involved in formation of carbonate precipitates to stimulate water absorption in marine teleost fish.

    PubMed

    Kurita, Yukihiro; Nakada, Tsutomu; Kato, Akira; Doi, Hiroyuki; Mistry, Abinash C; Chang, Min-Hwang; Romero, Michael F; Hirose, Shigehisa

    2008-04-01

    Marine teleost fish precipitate divalent cations as carbonate deposits in the intestine to minimize the potential for excessive Ca2+ entry and to stimulate water absorption by reducing luminal osmotic pressure. This carbonate deposit formation, therefore, helps maintain osmoregulation in the seawater (SW) environment and requires controlled secretion of HCO3(-) to match the amount of Ca2+ entering the intestinal lumen. Despite its physiological importance, the process of HCO3(-) secretion has not been characterized at the molecular level. We analyzed the expression of two families of HCO3(-) transporters, Slc4 and Slc26, in fresh-water- and SW-acclimated euryhaline pufferfish, mefugu (Takifugu obscurus), and obtained the following candidate clones: NBCe1 (an Na+-HCO3(-) cotransporter) and Slc26a6A and Slc26a6B (putative Cl(-)/HCO3(-) exchangers). Heterologous expression in Xenopus oocytes showed that Slc26a6A and Slc26a6B have potent HCO3(-)-transporting activity as electrogenic Cl(-)/nHCO3(-) exchangers, whereas mefugu NBCe1 functions as an electrogenic Na+-nHCO3(-) cotransporter. Expression of NBCe1 and Slc26a6A was highly induced in the intestine in SW and expression of Slc26a6B was high in the intestine in SW and fresh water, suggesting their involvement in HCO3(-) secretion and carbonate precipitate formation. Immunohistochemistry showed staining on the apical (Slc26a6A and Slc26a6B) and basolateral (NBCe1) membranes of the intestinal epithelial cells in SW. We therefore propose a mechanism for HCO3(-) transport across the intestinal epithelial cells of marine fish that includes basolateral HCO3(-) uptake (NBCe1) and apical HCO3(-) secretion (Slc26a6A and Slc26a6B). PMID:18216137

  9. The nondigestible disaccharide epilactose increases paracellular Ca absorption via rho-associated kinase- and myosin light chain kinase-dependent mechanisms in rat small intestines.

    PubMed

    Suzuki, Takuya; Nishimukai, Megumi; Takechi, Maki; Taguchi, Hidenori; Hamada, Shigeki; Yokota, Atsushi; Ito, Susumu; Hara, Hiroshi; Matsui, Hirokazu

    2010-02-10

    We previously showed that epilactose, a nondigestible disaccharide, increased calcium (Ca) absorption in the small intestines of rats. Here, we explored the mechanism(s) underlying the epilactose-mediated promotion of Ca absorption in a ligated intestinal segment of anesthetized rats. The addition of epilactose to the luminal solution increased Ca absorption and chromium (Cr)-EDTA permeability, a paracellular indicator, with a strong correlation (R = 0.93) between these changes. Epilactose induced the phosphorylation of myosin regulatory light chains (MLCs), which is known to activate the paracellular route, without any change in the association of tight junction proteins with the actin cytoskeleton. The epilactose-mediated promotion of the Ca absorption was suppressed by specific inhibitors of myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK). These results indicate that epilactose increases paracellular Ca absorption in the small intestine of rats through the induction of MLC phosphorylation via MLCK- and ROCK-dependent mechanisms.

  10. Effects of fasting and semistarvation on the kinetics of active and passive sugar absorption across the small intestine in vivo.

    PubMed Central

    Debnam, E S; Levin, R J

    1975-01-01

    The effects of dietary restriction on the kinetics of absorption in vivo of glucose, galactose and alpha-methyl glucoside were assessed by electrical and chemical methods in the rat jejunum. 2. The 'apparent Km', maximum absorption or Vmax (mu-mole/10 cm. 15 min) and maximum potential difference (p.d.max) were obtained for the jejunal electrogenic active transfer mechanism from the transfer p.d.s and the chemical absorption data corrected for diffusion using various graphical kinetic plots. 3. Fasting for 3 days greatly decreased the 'apparent Kms', obtained from electrical or chemical data, for all the sugars but had no effect on those for L-valine or L-methionine. Semistarvation caused a less pronounced reduction of the 'apparent Kms' for the sugars. The dietary-induced change in 'apparent Km' for glucose was also observed in the fasted hamster. One interpretation of these changes is that the affinity of the carriers for sugars increases during dietary restriction; the greater the level of restriction the greater the increase. 4. Fasting and semistarvation caused large reductions in the Vmax. These reductions were correlated with a reduced enterocyte population estimated by changes in enterocyte column size. 5. The reduction in the Vmax for galactose was mainly accounted for by the decrease in enterocyte population. In the case of glucose, other factors such as reduced enterocyte metabolism or changes in the carriers must be involved to explain the discrepancy between the large decrease in Vmax and the enterocyte column size. 6. Fasting and semi-starvation had complex, differential actions on the p.d.max for glucose, galactose and alpha-methyl glucoside. These changes did not correlate with those observed in the Vmax measured chemically. 7. A standard diet obtained from two commercial sources was found to differ greatly in its effect on the electrogenic transfer system for alpha-methyl glucoside but had no effect on those for galactose and glucose. PMID:1206572

  11. An evaluation of in vitro intestinal absorption of iron, calcium and potassium in chickens receiving gold nanoparticles.

    PubMed

    Sembratowicz, I; Ognik, K; Stępniowska, A

    2016-08-01

    This study evaluated the effect of oral administration of colloidal gold nanoparticles on accumulation of gold in the small intestine and intestinal absorption of iron, calcium and potassium under in vitro conditions. The gold nanoparticles are non-ionic, nanocrystalline, chemically pure particles 5 nm in size, produced in a physical process. In total, 126 one day-old Ross 308 chicks were assigned to 7 experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive gold nanoparticles. Groups: Au-5(7), Au-10(7) and Au-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg l(-1) for group Au-5(7), 10 mg l(-1) for group Au-10(7) and 15 mg l(-1) for group Au-15(7) in 8-14, 22-28 and 36-42 d of life. The birds in groups Au-5(3), Au-10(3) and Au-15(3) received gold nanoparticles in the same amounts, but only in 8-10, 22-24 and 36-38 d of life. The study revealed that nanogold supplied via ingestion leads to dose- and time-dependent accumulation of gold in the intestinal walls. Nanogold present in the jejunum has a negative impact on the absorption of calcium, iron and potassium under in vitro conditions.

  12. Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption.

    PubMed

    Ghosal, Abhisek; Lambrecht, Nils; Subramanya, Sandeep B; Kapadia, Rubina; Said, Hamid M

    2013-01-01

    The Slc5a6 gene expresses a plasma membrane protein involved in the transport of the water-soluble vitamin biotin; the transporter is commonly referred to as the sodium-dependent multivitamin transporter (SMVT) because it also transports pantothenic acid and lipoic acid. The relative contribution of the SMVT system toward carrier-mediated biotin uptake in the native intestine in vivo has not been established. We used a Cre/lox technology to generate an intestine-specific (conditional) SMVT knockout (KO) mouse model to address this issue. The KO mice exhibited absence of expression of SMVT in the intestine compared with sex-matched littermates as well as the expected normal SMVT expression in other tissues. About two-thirds of the KO mice died prematurely between the age of 6 and 10 wk. Growth retardation, decreased bone density, decreased bone length, and decreased biotin status were observed in the KO mice. Microscopic analysis showed histological abnormalities in the small bowel (shortened villi, dysplasia) and cecum (chronic active inflammation, dysplasia) of the KO mice. In vivo (and in vitro) transport studies showed complete inhibition in carrier-mediated biotin uptake in the intestine of the KO mice compared with their control littermates. These studies provide the first in vivo confirmation in native intestine that SMVT is solely responsible for intestinal biotin uptake. These studies also provide evidence for a casual association between SMVT function and normal intestinal health.

  13. SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells.

    PubMed

    Musch, M W; Bookstein, C; Xie, Y; Sellin, J H; Chang, E B

    2001-04-01

    Short-chain fatty acids (SCFA), produced by colonic bacterial flora fermentation of dietary carbohydrates, promote colonic Na absorption through mechanisms not well understood. We hypothesized that SCFA promote increased expression of apical membrane Na/H exchange (NHE), serving as luminal physiological cues for regulating colonic Na absorptive capacity. Studies were performed in human colonic C2/bbe (C2) monolayers and in vivo. In C2 cells exposed to butyrate, acetate, proprionate, or the poorly metabolized SCFA isobutyrate, apical membrane NHE3 activity and protein expression increased in a time- and concentration-dependent manner, whereas no changes were observed for NHE2. In contrast, no significant changes in brush-border hydrolase or villin expression were noted. Analogous to the in vitro findings, rats fed the soluble fiber pectin exhibited a time-dependent increase in colonic NHE3, but not NHE2, protein, mRNA, and brush-border activity. These changes were region-specific, as no changes were observed in the ileum. We conclude that luminal SCFA are important physiological cues for regulating colonic Na absorptive function, allowing the colon to adapt to chronic changes in dietary carbohydrate and Na loads.

  14. Lactobacillus acidophilus ATCC 4356 prevents atherosclerosis via inhibition of intestinal cholesterol absorption in apolipoprotein E-knockout mice.

    PubMed

    Huang, Ying; Wang, Jinfeng; Quan, Guihua; Wang, Xiaojun; Yang, Longfei; Zhong, Lili

    2014-12-01

    The objective of this study was to investigate the effect of Lactobacillus acidophilus ATCC 4356 on the development of atherosclerosis in apolipoprotein E-knockout (ApoE(-/-)) mice. Eight-week-old ApoE(-/-) mice were fed a Western diet with or without L. acidophilus ATCC 4356 daily for 16 weeks. L. acidophilus ATCC 4356 protected ApoE(-/-) mice from atherosclerosis by reducing their plasma cholesterol levels from 923 ± 44 to 581 ± 18 mg/dl, likely via a marked decrease in cholesterol absorption caused by modulation of Niemann-Pick C1-like 1 (NPC1L1). In addition, suppression of cholesterol absorption induced reverse cholesterol transport (RCT) in macrophages through the peroxisome proliferator-activated receptor/liver X receptor (PPAR/LXR) pathway. Fecal lactobacillus and bifidobacterium counts were significantly (P < 0.05) higher in the L. acidophilus ATCC 4356 treatment groups than in the control groups. Furthermore, L. acidophilus ATCC 4356 was detected in the rat small intestine, colon, and feces during the feeding trial. The bacterial levels remained high even after the administration of lactic acid bacteria had been stopped for 2 weeks. These results suggest that administration of L. acidophilus ATCC 4356 can protect against atherosclerosis through the inhibition of intestinal cholesterol absorption. Therefore, L. acidophilus ATCC 4356 may be a potential therapeutic material for preventing the progression of atherosclerosis.

  15. CTG-loaded liposomes as an approach for improving the intestinal absorption of asiaticoside in Centella Total Glucosides.

    PubMed

    Wang, Jiayu; Ma, Changhua; Guo, Chengjie; Yuan, Ruijuan; Zhan, Xueyan

    2016-07-25

    Centella Total Glucosides (CTG),obtained from Centella asiatica (L.), have been shown to possess a multitude of pharmacological activities, however, oral administeration of CTG failed to fulfill their therapeutic potentials due to the low bioavailability. In this study, the author prepared the liposomes encapsulated CTG using the ethanol injection method in order to enhance their intestinal absorption. The average particle size and the polydispersityindex(PDI) of CTG-loaded liposome in a batch are 137.0nm and 0.283, and the CTG-loaded amounts in CTG-loaded liposomes were 0.177mgmL(-1) and the zeta potential of CTG-loaded lipsomes is -21.2mV. The TEM images of CTG-loaded lipsomes showed that CTG-loaded liposomes are round and maintain high structural integrity, and their DSC thermograms indicated that CTG might be incorporated into the aqueous phase of DPPC to become more stable. The everted rat gut sac model was used to study the absorption characteristic of CTG-loaded solution in rat intestines. The cumulative absorption amount (Q) and the cumulative absorption percentage (P%) of asiaticoside in the CTG-loaded liposome was significantly higher than that in CTG (P<0.05), both the steady-state infiltration rate (Jss, μgcm(-2)s(-1)) and the permeability coefficient (Papp, cms(-1)) of asiaticoside in CTG-loaded liposomes were significantly higher than those in CTG (P<0.05), which revealed that the liposomes encapsulated CTG can promote the absorption of asiaticoside in the ileum of the rats by enhancing its transmembrane permeability. The above study will provide the experimental evidence and a reference for the development of the oral dosage forms of Centella total glucosides.

  16. Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption.

    PubMed

    Shitara, Yoshihisa; Maeda, Kazuya; Ikejiri, Kazuaki; Yoshida, Kenta; Horie, Toshiharu; Sugiyama, Yuichi

    2013-01-01

    Organic anion transporting polypeptide (OATP) family transporters accept a number of drugs and are increasingly being recognized as important factors in governing drug and metabolite pharmacokinetics. OATP1B1 and OATP1B3 play an important role in hepatic drug uptake while OATP2B1 and OATP1A2 might be key players in intestinal absorption and transport across blood-brain barrier of drugs, respectively. To understand the importance of OATPs in the hepatic clearance of drugs, the rate-determining process for elimination should be considered; for some drugs, hepatic uptake clearance rather than metabolic intrinsic clearance is the more important determinant of hepatic clearances. The importance of the unbound concentration ratio (liver/blood), K(p,uu) , of drugs, which is partly governed by OATPs, is exemplified in interpreting the difference in the IC(50) of statins between the hepatocyte and microsome systems for the inhibition of HMG-CoA reductase activity. The intrinsic activity and/or expression level of OATPs are affected by genetic polymorphisms and drug-drug interactions. Their effects on the elimination rate or intestinal absorption rate of drugs may sometimes depend on the substrate drug. This is partly because of the different contribution of OATP isoforms to clearance or intestinal absorption. When the contribution of the OATP-mediated pathway is substantial, the pharmacokinetics of substrate drugs should be greatly affected. This review describes the estimation of the contribution of OATP1B1 to the total hepatic uptake of drugs from the data of fold-increases in the plasma concentration of substrate drugs by the genetic polymorphism of this transporter. To understand the importance of the OATP family transporters, modeling and simulation with a physiologically based pharmacokinetic model are helpful.

  17. Supplementation with difructose anhydride III promotes passive calcium absorption in the small intestine immediately after calving in dairy cows.

    PubMed

    Teramura, M; Wynn, S; Reshalaitihan, M; Kyuno, W; Sato, T; Ohtani, M; Kawashima, C; Hanada, M

    2015-12-01

    The incidence of hypocalcemia increases in high-parity dairy cows because resorption of bone Ca is delayed in these animals, and they appear to have a reduced ability to absorb Ca from the intestine during the early postpartum period. Difructose anhydride (DFA) III has been shown to promote the absorption of intestinal Ca via a paracellular pathway. However, past studies have not reported this effect in peripartum dairy cows. Therefore, we investigated the effect of DFA III supplementation on Ca metabolism during the peripartum period to determine whether DFA III promotes intestinal Ca absorption via this route. Seventy-four multiparous Holstein cows were separated into DFA and control groups based on their parity and body weight. The feed of the DFA group was supplemented with 40g/d of DFA III from -14 to 6d relative to calving. The control group did not receive DFA III. At calving (0h relative to calving), serum Ca declined below 9mg/dL in both groups. However, serum Ca concentrations were greater in the DFA group than in the control group at 6, 12, 24, and 48h relative to calving, and the time required for serum Ca to recover to 9mg/dL during the postpartum period was shorter in the high-parity cows in the DFA group than in those in the control group. Parathyroid hormone concentrations increased immediately after calving in both groups and were greater in the control group than in the DFA group at 12 and 24h relative to calving. Serum 1,25-dihydroxyvitamin D concentrations increased at 0 and 12h relative to calving in both groups and were higher in the control group than in the DFA group at 72h relative to calving. Serum concentrations of the bone-resorption marker cross-linked N-telopeptide of type I collagen (NTX) were not different between the groups during peripartum period, and serum NTX in all cows was lower at 0, 6, 12, 24, 48, and 72h relative to calving than at -21, 4, and 5d relative to calving. Thus, DFA treatment induced faster recovery of serum Ca

  18. Conditional (intestinal-specific) knockout of the riboflavin transporter-3 (RFVT-3) impairs riboflavin absorption.

    PubMed

    Subramanian, Veedamali S; Lambrecht, Nils; Lytle, Christian; Said, Hamid M

    2016-02-15

    Riboflavin (RF) is indispensable for normal cell metabolism, proliferation, and growth. The RFVT-3 protein (product of the Slc52a3 gene) is expressed in the gut with the expression being restricted to the apical membrane domain of the polarized intestinal epithelial cells. The relative contribution of RFVT-3 to total carrier-mediated RF uptake in the native intestine, however, is not clear. We addressed this issue in the current investigation using a conditional (intestinal-specific) RFVT-3 knockout (cKO) mouse model developed by the Cre/Lox approach. All RFVT-3 cKO mice were found to be RF deficient and showed a significant growth and development retardation; also, nearly two-thirds of them died prematurely between the age of 6 and 12 wk. In vivo (intestinal and colonic loops) and in vitro (native isolated intestinal epithelial cells) uptake studies showed a severe inhibition in carrier-mediated RF uptake in the cKO mice compared with control littermates. We also observed a significant increase in the level of expression of oxidative stress-responsive genes in the intestine of the cKO mice compared with control littermates. Supplementation of the RFVT-3 cKO mice with pharmacological doses of RF led to a complete correction of the growth retardation and to normalization in the level of expression of the oxidative stress-responsive genes in the gut. These results show, for the first time, that the RFVT-3 system is the main transporter involved in carrier-mediated RF uptake in the native mouse small and large intestine, and that its dysfunction impairs normal RF body homeostasis.

  19. Absorption characteristic of paeoniflorin-6'-O-benzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats.

    PubMed

    Yang, Xiao-Dan; Wang, Chun; Zhou, Peng; Yu, Jun; Asenso, James; Ma, Yong; Wei, Wei

    2016-09-01

    1. Paeoniflorin-6'-O-benzene sulfonate (CP-25) was synthesized to improve the poor oral absorption of paeoniflorin (Pae). 2. This study was performed to investigate the absorptive behavior and mechanism of CP-25 in in situ single-pass intestinal perfusion in rats, using Pae as a control. 3. The results showed that intestinal absorption of CP-25 was neither segmental nor sex dependent. However, the main segment of intestine that absorbed Pae was the duodenum. Furthermore, passive transport was confirmed to be the main absorption pattern of CP-25. More importantly, the absorption of CP-25 was much higher than Pae in the small intestine. 4. Among the ABC transporter inhibitors, the absorption rate of Pae increased in the presence of P-gp inhibitors verapamil and GF120918, which indicated that Pae was a substrate of P-glycoprotein (P-gp), however, such was not observed in the presence of breast cancer resistance protein and multidrug resistance-associated protein 2. Finally, the ABC transporter inhibitors did not have any significant impact on CP-25 as demonstrated in the parallel studies. 5. CP-25 could improve the poor absorption of Pae, which may be attributed to both the lipid solubility enhancement and its resistance to P-gp-mediated efflux. PMID:26711120

  20. Absorption characteristic of paeoniflorin-6'-O-benzene sulfonate (CP-25) in in situ single-pass intestinal perfusion in rats.

    PubMed

    Yang, Xiao-Dan; Wang, Chun; Zhou, Peng; Yu, Jun; Asenso, James; Ma, Yong; Wei, Wei

    2016-09-01

    1. Paeoniflorin-6'-O-benzene sulfonate (CP-25) was synthesized to improve the poor oral absorption of paeoniflorin (Pae). 2. This study was performed to investigate the absorptive behavior and mechanism of CP-25 in in situ single-pass intestinal perfusion in rats, using Pae as a control. 3. The results showed that intestinal absorption of CP-25 was neither segmental nor sex dependent. However, the main segment of intestine that absorbed Pae was the duodenum. Furthermore, passive transport was confirmed to be the main absorption pattern of CP-25. More importantly, the absorption of CP-25 was much higher than Pae in the small intestine. 4. Among the ABC transporter inhibitors, the absorption rate of Pae increased in the presence of P-gp inhibitors verapamil and GF120918, which indicated that Pae was a substrate of P-glycoprotein (P-gp), however, such was not observed in the presence of breast cancer resistance protein and multidrug resistance-associated protein 2. Finally, the ABC transporter inhibitors did not have any significant impact on CP-25 as demonstrated in the parallel studies. 5. CP-25 could improve the poor absorption of Pae, which may be attributed to both the lipid solubility enhancement and its resistance to P-gp-mediated efflux.

  1. The influence of lactose intolerance and other gastro-intestinal tract disorders on L-thyroxine absorption.

    PubMed

    Ruchała, Marek; Szczepanek-Parulska, Ewelina; Zybek, Ariadna

    2012-01-01

    The preferred treatment for hypothyroidism is oral levothyroxine (LT4) ingestion, in doses that ensure a sustained state of hormonal balance. Many different factors may significantly influence the absorption of LT4, including: interval between the ingestion of the drug and the last meal, eating habits, and different functional and organic pathologies of the gastro-intestinal tract. The main purpose of this paper is to review and systematise the available literature on the subject of the influence of different malabsorption syndromes on the effectiveness of LT4 preparations. The need to use high LT4 doses in the substitutional treatment of hypothyroidism is often the very first sign of one of the pathologies that are connected with malabsorption syndrome, which might have been asymptomatic and undiagnosed previously. Patients who require more than 2 μg/kg body weight of LT4 per day, with constantly increased thyrotropin level, should be diagnosed with the suspicion of pseudomalabsorption or real absorption disorder. An LT4 absorption test, using high doses of LT4, may be useful in the diagnosis of pseudomalabsorption. After excluding non-compliance, the differential diagnosis should include such disorders as lactose intolerance, coeliac disease, atrophic gastritis, Helicobacter pylori infection, bowel resection, inflammatory bowel disease, and parasite infection. Where there is a diagnosis of lactose intolerance, both a low lactose diet and a lactose-free LT4 preparation should be administered to restore euthyroidism or make it possible to decrease the dose of the LT4 preparation. In coeliac disease, a gluten-free diet usually allows a normalisation of the need for LT4, as do eradication of the H. pylori infection or parasite colonisation. In cases of atrophic gastritis or inflammatory bowel disease, treating the underlying diseases and regaining the state of remission may improve the absorption of LT4. In patients after gastro-intestinal tract surgery, a dose of

  2. Intestinal solubility and absorption of poorly water soluble compounds: predictions, challenges and solutions.

    PubMed

    Fagerberg, Jonas H; Bergström, Christel A S

    2015-01-01

    We have explored for which type of compounds biorelevant dissolution profiling in simulated intestinal fluids would accurately predict solubility in human intestinal fluid. In total, 460 solubility values in simulated and aspirated human intestinal fluid for 78 drugs were compiled and analyzed. Significant solubilization in the colloidal structures was obtained in fasted and fed state fluids for drug compounds with a logD(oct)>3. Highly lipophilic compounds with high melting points (Tm > 200 °C) could also be significantly solubilized, but typically such compounds had solubility values in the lower µg/ml range also in the presence of the colloidal structures. On the basis of our analysis, compounds with a logD(oct)>3 should be explored in biorelevant dissolution media to better predict in vivo performance after oral dosing.

  3. Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine.

    PubMed

    Mace, Oliver J; Morgan, Emma L; Affleck, Julie A; Lister, Norma; Kellett, George L

    2007-04-15

    Glucose absorption in rat jejunum involves Ca(2+)- and PKC betaII-dependent insertion of GLUT2 into the apical membrane. Ca(2+)-induced rearrangement of the enterocyte cytoskeleton is thought to enhance paracellular flow. We have therefore investigated the relationships between myosin II regulatory light chain phosphorylation (RLC(20)), absorption of glucose, water and calcium, and mannitol clearance. ML-7, an inhibitor of myosin light chain kinase, diminished the phloretin-sensitive apical GLUT2 but not the phloretin-insensitive SGLT1 component of glucose absorption in rat jejunum perfused with 75 mM glucose. Western blotting and immunocytochemistry revealed marked decreases in RLC(20) phosphorylation in the terminal web and in the levels of apical GLUT2 and PKC betaII, but not SGLT1. Perfusion with phloridzin or 75 mM mannitol, removal of luminal Ca(2+), or inhibition of unidirectional (45)Ca(2+) absorption by nifedipine exerted similar effects. ML-7 had no effect on the absorption of 10 mM Ca(2+), nor clearance of [(14)C]-mannitol, which was less than 0.7% of the rate of glucose absorption. Water absorption did not correlate with (45)Ca(2+) absorption or mannitol clearance. We conclude that the Ca(2+) necessary for contraction of myosin II in the terminal web enters via an L-type channel, most likely Ca(v)1.3, and is dependent on SGLT1. Moreover, terminal web RLC(20) phosphorylation is necessary for apical GLUT2 insertion. The data confirm that glucose absorption by paracellular flow is negligible, and show further that paracellular flow makes no more than a minimal contribution to jejunal Ca(2+) absorption at luminal concentrations prevailing after a meal.

  4. Effects of citronellal, a monoterpenoid in Zanthoxyli Fructus, on the intestinal absorption of digoxin in vitro and in vivo.

    PubMed

    Yoshida, Naoko; Takagi, Akiyoshi; Kitazawa, Hidenori; Kawakami, Junichi; Adachi, Isao

    2006-03-01

    Complementary and alternative medicines can be applied concomitantly with conventional medicines; however, little drug information is available on these interactions. Previously, we reported on the inhibitory effects of an extract and monoterpenoids (e.g., (R)-(+)-citronellal) contained in citrus herbs on P-glycoprotein (P-gp) using P-gp-overexpressed LLC-PK1 cells. The objective of the present study was to investigate the effects of (R)-(+)-citronellal on P-gp-mediated transport in the intestinal absorption process in vitro and in vivo. Transcellular transport of [(3)H]digoxin across Caco-2 cell monolayers was measured in the presence or absence of (R)-(+)-citronellal. (R)-(+)-citronellal reduced the basolateral-to-apical transport and efflux ratio for [(3)H]digoxin significantly. Serum concentration-time profiles and pharmacokinetic parameters of digoxin after intravenous and oral administration were analyzed in rats pretreated with oral (R)-(+)-citronellal. The bioavailability of digoxin after oral administration decreased significantly to 75.8% of that after intravenous administration at the same dose. (R)-(+)-citronellal increased the bioavailability of oral digoxin to 99.9% but had no effects on total body clearance, volume of distribution, or elimination rate. These findings suggest that (R)-(+)-citronellal can increase the bioavailability of oral digoxin based on the blockade of P-gp-mediated efflux of digoxin from intestinal epithelia to the lumen in the absorption process.

  5. Effect of medium-chain glycerides on the membrane transport of D-glucose and sulfanilic acid in the intestinal brush-border membrane vesicles.

    PubMed

    Sagara, K; Higaki, K; Yamazaki, A; Hashida, M; Sezaki, H

    1990-01-01

    To clarify the influence of medium-chain glycerides (MCG) on a biological membrane, we investigated the membrane transport of D-glucose and sulfanilic acid in the brush-border membrane (BBM) vesicles pretreated with MCG. The size distribution of the BBM vesicles determined by electron microscopic observation was not significantly different between the vesicles incorporated with MCG and those of the control. However, the amount of D-glucose taken up by the vesicles at an equilibrated stage (30 min) was significantly decreased in the MCG-treated ones based on unit content of protein. Based on these results we estimated the membrane transport of D-glucose and sulfanilic acid in consideration of vesiculation or filter-capturing efficiency in MCG-treated vesicles. The rates of Na+ gradient-independent D-glucose transport and sulfanilic acid transport were significantly greater in MCG-treated vesicles than in the control. On the other hand, the magnitude of overshooting effect in Na+ gradient-dependent uptake of D-glucose in MCG-treated vesicles was maintained similar to the control. Comparison of kinetic parameters for active D-glucose transport at different concentrations indicated that Km and Vmax were not significantly different between MCG-treated and the control vesicles. These results indicated that passive diffusion of D-glucose and sulfanilic acid was significantly increased but Na(+)-glucose cotransporter was not significantly changed by the incorporation of MCG in the intestinal BBM vesicles.

  6. Adolescence: How do we increase intestinal calcium absorption to allow for bone mineral mass accumulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An increase in calcium absorptive efficiency (fractional absorption of dietary calcium) during adolescence is associated with a rapid increase in total body bone mineral mass (BMM) accumulation. This increase occurs across a range of calcium intakes. It appears to be principally mediated by hormonal...

  7. HCO (3)(-) secretion and CaCO3 precipitation play major roles in intestinal water absorption in marine teleost fish in vivo.

    PubMed

    Whittamore, Jonathan M; Cooper, Christopher A; Wilson, Rod W

    2010-04-01

    The intestine of marine teleosts must effectively absorb fluid from ingested seawater to avoid dehydration. This fluid transport has been almost exclusively characterized as driven by NaCl absorption. However, an additional feature of the osmoregulatory role of the intestine is substantial net HCO(3)(-) secretion. This is suggested to drive additional fluid absorption directly (via Cl(-)/HCO(3)(-) exchange) and indirectly by precipitating ingested Ca(2+) as CaCO(3), thus creating the osmotic gradient for additional fluid absorption. The present study tested this hypothesis by perfusing the intestine of the European flounder in vivo with varying [Ca(2+)]: 10 (control), 40, and 90 mM. Fractional fluid absorption increased from 47% (control) to 73% (90 mM Ca(2+)), where almost all secreted HCO(3)(-) was excreted as CaCO(3). This additional fluid absorption could not be explained by NaCl cotransport. Instead, a significant positive relationship between Na(+)-independent fluid absorption and total HCO(3)(-) secretion was consistent with the predicted roles for anion exchange and CaCO(3) precipitation. Further analysis suggested that Na(+)-independent fluid absorption could be accounted for by net Cl(-) and H(+) absorption (from Cl(-)/HCO(3)(-) exchange and CO(2) hydration, respectively). There was no evidence to suggest that CaCO(3) alone was responsible for driving fluid absorption. However, by preventing the accumulation of luminal Ca(2+) it played a vital role by dynamically maintaining a favorable osmotic gradient all along the intestine, which permits substantially higher rates of solute-linked fluid absorption. To overcome the resulting hyperosmotic and highly acidic absorbate, it is proposed that plasma HCO(3)(-) buffers the absorbed H(+) (from HCO(3)(-) production), and consequently reduces the osmolarity of the absorbed fluid entering the body. PMID:20130226

  8. High or low dietary carbohydrate:protein ratios during first-feeding affect glucose metabolism and intestinal microbiota in juvenile rainbow trout.

    PubMed

    Geurden, I; Mennigen, J; Plagnes-Juan, E; Veron, V; Cerezo, T; Mazurais, D; Zambonino-Infante, J; Gatesoupe, J; Skiba-Cassy, S; Panserat, S

    2014-10-01

    Based on the concept of nutritional programming in mammals, we tested whether an acute hyperglucidic-hypoproteic stimulus during first feeding could induce long-term changes in nutrient metabolism in rainbow trout. Trout alevins received during the five first days of exogenous feeding either a hyperglucidic (40% gelatinized starch + 20% glucose) and hypoproteic (20%) diet (VLP diet) or a high-protein (60%) glucose-free diet (HP diet, control). Following a common 105-day period on a commercial diet, both groups were then challenged (65 days) with a carbohydrate-rich diet (28%). Short- and long-term effects of the early stimuli were evaluated in terms of metabolic marker gene expressions and intestinal microbiota as initial gut colonisation is essential for regulating the development of the digestive system. In whole alevins (short term), diet VLP relative to HP rapidly increased gene expressions of glycolytic enzymes, while those involved in gluconeogenesis and amino acid catabolism decreased. However, none of these genes showed persistent molecular adaptation in the liver of challenged juveniles (long term). By contrast, muscle of challenged juveniles subjected previously to the VLP stimulus displayed downregulated expression of markers of glycolysis and glucose transport (not seen in the short term). These fish also had higher plasma glucose (9 h postprandial), suggesting impaired glucose homeostasis induced by the early stimulus. The early stimulus did not modify the expression of the analysed metabolism-related microRNAs, but had short- and long-term effects on intestinal fungi (not bacteria) profiles. In summary, our data show that a short hyperglucidic-hypoproteic stimulus during early life may have a long-term influence on muscle glucose metabolism and intestinal microbiota in trout.

  9. High or low dietary carbohydrate:protein ratios during first-feeding affect glucose metabolism and intestinal microbiota in juvenile rainbow trout.

    PubMed

    Geurden, I; Mennigen, J; Plagnes-Juan, E; Veron, V; Cerezo, T; Mazurais, D; Zambonino-Infante, J; Gatesoupe, J; Skiba-Cassy, S; Panserat, S

    2014-10-01

    Based on the concept of nutritional programming in mammals, we tested whether an acute hyperglucidic-hypoproteic stimulus during first feeding could induce long-term changes in nutrient metabolism in rainbow trout. Trout alevins received during the five first days of exogenous feeding either a hyperglucidic (40% gelatinized starch + 20% glucose) and hypoproteic (20%) diet (VLP diet) or a high-protein (60%) glucose-free diet (HP diet, control). Following a common 105-day period on a commercial diet, both groups were then challenged (65 days) with a carbohydrate-rich diet (28%). Short- and long-term effects of the early stimuli were evaluated in terms of metabolic marker gene expressions and intestinal microbiota as initial gut colonisation is essential for regulating the development of the digestive system. In whole alevins (short term), diet VLP relative to HP rapidly increased gene expressions of glycolytic enzymes, while those involved in gluconeogenesis and amino acid catabolism decreased. However, none of these genes showed persistent molecular adaptation in the liver of challenged juveniles (long term). By contrast, muscle of challenged juveniles subjected previously to the VLP stimulus displayed downregulated expression of markers of glycolysis and glucose transport (not seen in the short term). These fish also had higher plasma glucose (9 h postprandial), suggesting impaired glucose homeostasis induced by the early stimulus. The early stimulus did not modify the expression of the analysed metabolism-related microRNAs, but had short- and long-term effects on intestinal fungi (not bacteria) profiles. In summary, our data show that a short hyperglucidic-hypoproteic stimulus during early life may have a long-term influence on muscle glucose metabolism and intestinal microbiota in trout. PMID:25274323

  10. Fate of ingested fluids: factors affecting gastric emptying and intestinal absorption of beverages in humans.

    PubMed

    Leiper, John B

    2015-09-01

    The volume of fluid ingested for rehydration is essential in determining the restoration of euhydration because it must be in excess of the water lost since the individual was last euhydrated. The formulation of any ingested beverage is also important as this affects the rate at which the fluid is emptied from the stomach, absorbed in the small intestine, and hence assimilated into the body water pool. This review highlights the essential role of the gastrointestinal tract in the maintenance of hydration status.

  11. Dependence of intestinal iron absorption on the valency state of iron.

    PubMed

    Wollenberg, P; Rummel, W

    1987-11-01

    1. In rats iron was absorbed after administration into the gut lumen as ferric iron bound to serum albumin, to nitrilotriacetic acid, and to 8-OH-quinoline sulfonic acid, or as isolated diferri-transferrin. 2. Iron absorption from 59Fe-labelled transferrin was inhibited by the addition of rat plasma. 3. The inhibitory component in the rat plasma turned out to be ceruloplasmin (ferrous iron oxidase, EC 1.16.2.1). 4. The absorption of iron from these ferric iron complexes was also inhibited by addition to the incubation medium of ferrozine, a strong anionic Fe(II)-ligand. 5. Uptake and absorptive utilization of transferrin-bound ferric iron was decreased after a prewash of the gut lumen and could be restored by the addition of ascorbate to the incubation medium. 6. The conclusion was drawn from these results that luminal reduction precedes ferric iron absorption and that this is a prerequisite for the uptake into the mucosa.

  12. Evaluation of intestinal absorption of ginsenoside Rg1 incorporated in microemulison using parallel artificial membrane permeability assay.

    PubMed

    Han, Min; Fu, Shao; Gao, Jian-Qing; Fang, Xiao-Ling

    2009-06-01

    In the present study, ginsenoside Rg(1) (Rg(1)), a naturally occurring drug which is hardly absorbed in gastrointestinal (GI) tract due to its high hydrophilicity and low membrane permeability, was incorporated in different compositions of water-in-oil microemulsions (MEs). And parallel artificial membrane permeability assay (PAMPA) that have been mainly utilized for the evaluation of in vitro permeability of early drug candidates was introduced in present study, as well as rat in vivo pharmacokinetics and in vitro permeability measurements, to investigate the effect of w/o ME on Rg(1) absorption. Correlation between various models as mentioned above was further performed to estimate the feasibility of PAMPA in the application of pharmaceutical preparation studies. After being administrated intraduodenally to rats, most of MEs can enhance the intestinal absorption of Rg(1) to various extents with relative bioavailability (F(re)) ranging from 268 to 1270% using drug solution as control. This enhanced absorption of Rg(1) may be related to its increased membrane permeability induced by ME as exhibited in the PAMPA and rat in vitro permeability measurements. Meanwhile, rat in vivo pharmacokinetics-PAMPA correlation (r(2)=0.6082) is significant (p<0.05) for ME, representing a potential prospect for the application of PAMPA in the study of pharmaceutical preparation in some conditions. PMID:19483317

  13. Dissolution and absorption modeling: model expansion to simulate the effects of precipitation, water absorption, longitudinally changing intestinal permeability, and controlled release on drug absorption.

    PubMed

    Johnson, Kevin C

    2003-09-01

    A previously described model for simulating drug dissolution, absorption, and pharmacokinetics has been expanded beyond the original application of simulating immediate-release dosage forms to include simulation of drug precipitation, water absorption from the gastrointestinal tract, changing gastrointestinal permeability, disintegration, and controlled-release and dissolution from a GITS-type dosage form. A mathematical description of the model is presented as well as a retrospective analysis of nifedipine to demonstrate the utility of the model. The fourth-order Runge-Kutta numerical method was used to solve the series of coupled differential equations used to simulate the process of dissolution, absorption, and drug disposition. The model was able to simulate the clinically demonstrated effect for drug particle size on nifedipine plasma concentrations for an immediate-release dosage form. Further simulations indicated that drug particle size was less important for a GITS-type dosage form at a release rate of 1.7 mg/hr compared to rate of 17 mg/hr. Hypothetical calculations simulated the potential effect of drug precipitation, water absorption, and changing permeability on drug plasma concentrations. The expanded model increases the utility of a previously described model in providing guidance in drug development and selection.

  14. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx.

    PubMed

    Kuhre, Rune Ehrenreich; Bechmann, Louise Ellegaard; Wewer Albrechtsen, Nicolai Jacob; Hartmann, Bolette; Holst, Jens Juul

    2015-06-15

    Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-α-D-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct KATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of KATP channels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.

  15. Comparative study of the intestinal absorption of three salts of calcium in young and elderly women.

    PubMed

    Praet, J P; Peretz, A; Mets, T; Rozenberg, S

    1998-04-01

    A daily ingestion of 1000 to 1500 mg elemental calcium associated with vitamin D supplement is presently considered to be the adequate and least expensive therapy for senile osteoporosis. There exists only scarce data about calcium absorption with available calcium salts in elderly patients. We have compared the digestive absorption of calcium (Ca) citrate in soluble and solid form and calcium gluconolactate-carbonate in 15 young and 20 elderly, healthy women using the oral calcium loading test. The subjects were divided into two groups. In the first group, the absorption of solid Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) both in young (n = 7) and elderly women (n = 10). In the second group, the absorption of soluble Ca citrate (1000 mg Ca element) was compared to the absorption of Ca gluconolactate-carbonate (1000 mg Ca element) in young (n = 8) and elderly (n = 10) women. In the preload phase, basal calciuria was increased in elderly women (p < 0.01) although basal calcemia was similar in young and elderly women. After oral administration of the calcium salts, an increase in plasma Ca was observed in both groups which was greater for soluble Ca citrate and Ca gluconolactate than for solid Ca citrate. In young women, the increase in plasma calcium was significantly higher with soluble Ca citrate compared to Ca gluconolactate (p < 0.05). In elderly women, the postload calciuria was significantly higher for soluble Ca citrate (p < 0.05) and Ca gluconolactate (p < 0.05) compared to solid Ca citrate. A similar pattern was observed in young women, although it was not significant. In conclusion, an oral load of 1000 mg soluble Ca citrate and Ca gluconolactate-carbonate induces significant biochemical changes suggesting a better digestive absorption compared to Ca citrate in solid form, both in young and elderly women. We did not observe different response, between young and old patients. PMID

  16. Transcellular oxalate and Cl- absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate.

    PubMed

    Freel, Robert W; Whittamore, Jonathan M; Hatch, Marguerite

    2013-10-01

    Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA in intestinal oxalate and Cl(-) transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild-type (WT) and DRA knockout (KO) mice. In WT mice, all segments demonstrated net oxalate and Cl(-) absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion, which was consistently, and solely, due to a significant reduction in the absorptive unidirectional fluxes. In KO mice, daily urinary oxalate excretion was reduced 66% compared with that in WT mice, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and Cl(-) absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscore the importance of transcellular intestinal oxalate absorption, in general, and, more specifically, the importance of the DRA exchanger in oxalate homeostasis.

  17. Slowly digestible starch diets alter proximal glucosidase activity and glucose absorption

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sucrase-isomaltase (Si) and maltase-glucoamylase (Mgam) are mucosal glucosidases required for digestion of starch to glucose. Ablation of maltase-Mgam reduces in vivo starch digestion. We tested whether slowly digestible starch diets induce changes in glucosidase activities. Rice starch was encaps...

  18. The Small Intestinal Epithelia of Beef Steers Differentially Express Sugar Transporter Messenger Ribonucleic Acid in Response to Abomasal Versus Ruminal Infusion of Starch Hydrolysate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In mammals, the absorption of mono¬saccharides from small intestinal lumen involves at least 3 sugar transporters (SugT): sodium-dependent glucose transporter 1 (SGLT1; gene SLC5A1) transports glucose and galactose, whereas glucose transporter (GLUT) 5 (GLUT5; gene SLC2A5) transports fructose, acros...

  19. Interaction of taurine on baclofen intestinal absorption: a nonlinear mathematical treatment using differential equations to describe kinetic inhibition models.

    PubMed

    Moll-Navarro, M J; Merino, M; Casabó, V G; Nácher, A; Polache, A

    1996-11-01

    Previous studies showed that the in situ absorption of baclofen in rat jejunum was inhibited by beta-alanine, a nonessential amino acid, and therefore mediated, at least in part, by some beta-amino acid carrier. In this paper a similar study was undertaken using taurine, a sulfonic beta-amino acid, in order to evaluate its effect and to establish a general inhibition model. To achieve this goal, remaining concentrations of inhibitor were also measured and incorporated into the model. Previously, kinetic absorption in situ parameters for taurine in free solution were obtained: Vm = 27.73 +/- 9.99 mM h-1, K(m) = 8.06 +/- 2.82 mM, Ka (passive difussion component) = 0.40 +/- 0.28 h-1. Isotonic solutions containing 0.5 mM baclofen with starting taurine concentrations ranging from 0 to 100 mM were perfused in rat jejunum, and the remaining concentrations of both compounds were measured. The apparent rate pseudoconstant of the drug clearly decreased as the remaining taurine concentration increased. The interaction can be described as a complete competitive inhibition plus a second component, K, noninhibited, K = 0.58 (+/- 0.03) h-1, Ki = 20.62 (+/- 4.04) mM, Vmi = 28.12 (+/- 6.12) mM h-1, Kmi = 11.71 (+/- 2.53) mM, Kai = 0.47 (+/- 0.10) h-1. A residual absorption of baclofen in the presence of high taurine concentrations was observed, which should be attributed to another transport system not associated with the taurine carrier. In order to elucidate whether or not taurine and beta-alanine carriers are two separate entities that baclofen can use for absorption, further experiments using beta-alanine and taurine together as inhibitors (baclofen, 0.5 mM; beta-alanine, 50 mM, and taurine, 50 mM) were developed. Results indicated that baclofen and both amino acids share the same carrier in the intestinal absorption process. We have completed studies using leucine, taurine, and GABA together as inhibitors of drug absorption. An isotonic perfusion solution of 0.5 mM baclofen in

  20. Translating Human Effective Jejunal Intestinal Permeability to Surface-Dependent Intrinsic Permeability: a Pragmatic Method for a More Mechanistic Prediction of Regional Oral Drug Absorption.

    PubMed

    Olivares-Morales, Andrés; Lennernäs, Hans; Aarons, Leon; Rostami-Hodjegan, Amin

    2015-09-01

    Regional intestinal effective permeability (P(eff)) values are key for the understanding of drug absorption along the whole length of the human gastrointestinal (GI) tract. The distal regions of the GI tract (i.e. ileum, ascending-transverse colon) represent the main sites for GI absorption when there is incomplete absorption in the upper GI tract, e.g. for modified release formulations. In this work, a new and pragmatic method for the estimation of (passive) intestinal permeability in the different intestinal regions is being proposed, by translating the observed differences in the available mucosal surface area along the human GI tract into corrections of the historical determined jejunal P(eff) values. These new intestinal P(eff) values or "intrinsic" P(eff)(P(eff,int)) were subsequently employed for the prediction of the ileal absorption clearance (CL(abs,ileum)) for a set of structurally diverse compounds. Additionally, the method was combined with a semi-mechanistic absorption PBPK model for the prediction of the fraction absorbed (f(abs)). The results showed that P(eff,int) can successfully be employed for the prediction of the ileal CL(abs) and the f(abs). P(eff,int) also showed to be a robust predictor of the f(abs) when the colonic absorption was allowed in the PBPK model, reducing the overprediction of f(abs) observed for lowly permeable compounds when using the historical P(eff) values. Due to its simplicity, this approach provides a useful alternative for the bottom-up prediction of GI drug absorption, especially when the distal GI tract plays a crucial role for a drug's GI absorption.

  1. The effect of canola meal tannins on the intestinal absorption capacity of broilers using a D-xylose test.

    PubMed

    Mansoori, B; Rogiewicz, A; Slominski, B A

    2015-12-01

    In three D-xylose absorption experiments, the effect of 1% HCl/methanol, 70% methanol or 70% acetone extracts of canola meal (CM) or 70% acetone extract of soybean meal (SBM) containing polyphenols, phenolic acids, tannins and phytic acid on intestinal absorption capacity of broilers was determined. In Exp. 1, the experimental groups received orally D-xylose solution alone or with methanol/HCl, methanol or acetone extracts of CM. In Exp. 2, the experimental groups received D-xylose alone or with acetone extracts of CM or SBM. In Exp. 3, the experimental groups received D-xylose plus sucrose solution or D-xylose plus acetone extracts of CM or SBM. In Exps. 2 and 3, the CM extracts contained 2.7 and 2.6, 2.4 and 2.3, 3.2 and 3.2, and 2.4 and 2.2 times higher polyphenols, phenolic acids, tannins and condensed tannins than the corresponding SBM extracts respectively. Blood samples were collected in 40-min intervals, and plasma D-xylose was measured. Compared to the Control, plasma D-xylose in Exp. 1 was lower (p < 0.001) by 81, 69 and 73% at 40-min, by 41, 44 and 37% at 80-min and by 22, 31, and 23% at 120-min post-ingestion of the HCl/methanol, methanol and acetone extracts respectively. In both Exps. 2 and 3, plasma D-xylose level was lower (p < 0.001) in groups dosed with CM extract or SBM extract at each time of blood collection, when compared to the respective Control group. However, in Exp. 3, birds dosed with SBM extract had higher plasma D-xylose than CM extract-dosed birds by 28, 8 and 21% at 40, 80 and 120 min respectively (p < 0.01). In conclusion, although CM extract caused a lower absorption of D-xylose, based on 5 to 10% of CM inclusion levels in practical broiler rations, the soluble bioactive components of CM will likely have minor impact on the absorption capacity of the chicken intestine.

  2. Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.

    PubMed

    Takatsuka, Shinya; Kitazawa, Takeo; Morita, Takahiro; Horikiri, Yuji; Yoshino, Hiroyuki

    2006-01-01

    The effect of co-administration of a mucolytic agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a mucolytic agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs. PMID:16289777

  3. Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.

    PubMed

    Takatsuka, Shinya; Kitazawa, Takeo; Morita, Takahiro; Horikiri, Yuji; Yoshino, Hiroyuki

    2006-01-01

    The effect of co-administration of a mucolytic agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a mucolytic agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs.

  4. Effects of glycerides on the intestinal absorption of cyclosporine a using the in-situ mesenteric vein cannulated rat model.

    PubMed

    Ghorab, Mamdouh M; Abdel-Salam, Heba M; Abdel-Moate, Mohamed M

    2005-07-01

    The purpose of this study was to evaluate and compare the effect of glycerides with different fatty acid distributions (e.g. Arlacel 186, Capmul GMO and Captex 350) on Cyclosporine absorption in rat ileum segment using the modified single-pass intestinal perfusion with mesenteric vein cannulation. Drug concentration in the perfusate and blood plasma was analyzed by HPLC; and permeability coefficients were calculated from drug appearance in blood (P(blood)) and disappearance from perfusate (P(lumen)). Particle size was measured using Malvern Zetasaizer 1000HSA. Rheologic properties were measured using Brookfield viscometer. The results show that the average particle sizes after dilution (100 folds) of formulae containing Arlacel 186, Capmul GMO and Captex 350 and containing 0.8 mM CsA were 260+/-35.8, 130+/-11.4 and 37.5+/-6.0 nm, respectively. The polydispersity index was 0.6, 0.7 and 0.108 for formulations with Arlacel 186, Capmul GMO and Captex 350, respectively. CsA permeability coefficients (P(blood)) calculated from drug appearance in the blood in presence of Arlacel 186, Capmul GMO and Captex 350 were 0.3x10(-6), 1.0x10(-6) and 1.7x10(-6) cm2/sec, respectively. Phenol red was used as a water marker to determine net water absorption and secretion. Its constant concentration suggested that formulation did not alter intestinal water flux. From the results we can conclude that degree of glyceride esterification has a potential impact on the average particle size distribution and polydispersity of the formed micelles on dilution, which on turn contribute to the interaction between membrane and drug.

  5. Effects of the mucoadhesive polymer polycarbophil on the intestinal absorption of a peptide drug in the rat.

    PubMed

    Lehr, C M; Bouwstra, J A; Kok, W; De Boer, A G; Tukker, J J; Verhoef, J C; Breimer, D D; Junginger, H E

    1992-05-01

    The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.

  6. Absorption Mechanism of a Physical Complex of Monomeric Insulin and Deoxycholyl-l-lysyl-methylester in the Small Intestine.

    PubMed

    Mahmud, Foyez; Jeon, Ok-Cheol; Al-Hilal, Taslim A; Kweon, Seho; Yang, Victor C; Lee, Dong Soo; Byun, Youngro

    2015-06-01

    Currently, oral administration of insulin still remains the best option to avoid the burden of repeated subcutaneous injections and to improve its pharmacokinetics. The objective of the present investigation was to demonstrate the absorption mechanism of insulin in the physical complexation of deoxycholyl-l-lysyl-methylester (DCK) for oral delivery. The oral insulin/DCK complex was prepared by making a physical complex of insulin aspart with DCK through ion-pair interaction in water. For the cellular uptake study, fluorescein-labeled insulin or DCK were prepared according to a standard protocol and applied to Caco-2 or MDCK cell lines. For the PK/PD studies, we performed intrajejunal administration of different formulation of insulin/DCK complex to diabetic rats. The resulting insulin and DCK complex demonstrated greatly enhanced lipophilicity as well as increased permeation across Caco-2 monolayers. The immunofluorescence study revealed the distribution of the complex in the cytoplasm of Caco-2 cells. Moreover, in the apical sodium bile acid transporter (ASBT) transfected MDCK, the insulin/DCK complex showed interaction with ASBT, and also demonstrated absorption through passive diffusion. We could not find that any evidence of endocytosis in relation to the uptake of insulin complex in vitro. In the rat intestine model, the highest absorption of insulin complex was observed in the jejunum at 1 h and then in the ileum at 2-4 h. In PK/PD study, the complex showed a similar PK profile to that of SC insulin. Overall, the study showed that the effect of DCK on enhancing the absorption of insulin resulted from transcellular processes as well as bile acid transporter activity.

  7. Involvement of the Niacin Receptor GPR109a in the LocalControl of Glucose Uptake in Small Intestine of Type 2Diabetic Mice.

    PubMed

    Wong, Tung Po; Chan, Leo Ka Yu; Leung, Po Sing

    2015-09-08

    Niacin is a popular nutritional supplement known to reduce the risk of cardiovascular diseases by enhancing high-density lipoprotein levels. Despite such health benefits, niacin impairs fasting blood glucose. In type 2 diabetes (T2DM), an increase in jejunal glucose transport has been well documented; however, this is intriguingly decreased during niacin deficient state. In this regard, the role of the niacin receptor GPR109a in T2DM jejunal glucose transport remains unknown. Therefore, the effects of diabetes and high-glucose conditions on GPR109a expression were studied using jejunal enterocytes of 10-week-old m+/db and db/db mice, as well as Caco-2 cells cultured in 5.6 or 25.2 mM glucose concentrations. Expression of the target genes and proteins were quantified using real-time polymerase chain reaction (RT-PCR) and Western blotting. Glucose uptake in Caco-2 cells and everted mouse jejunum was measured using liquid scintillation counting. 10-week T2DM increased mRNA and protein expression levels of GPR109a in jejunum by 195.0% and 75.9%, respectively, as compared with the respective m+/db control; high-glucose concentrations increased mRNA and protein expression of GPR109a in Caco-2 cells by 130.2% and 69.0%, respectively, which was also confirmed by immunohistochemistry. In conclusion, the enhanced GPR109a expression in jejunal enterocytes of T2DM mice and high-glucose treated Caco-2 cells suggests that GPR109a is involved in elevating intestinal glucose transport observed in diabetes.

  8. Near-Infrared Studies of Glucose and Sucrose in Aqueous Solutions: Water Displacement Effect and Red Shift in Water Absorption from Water-Solute Interaction

    NASA Astrophysics Data System (ADS)

    Jung, Youngeui; Hwang, Jungseek

    2013-02-01

    We use near infrared spectroscopy to obtain concentration dependent glucose absorption spectra in their aqueous solutions in the near-infrared range (3800 - 7500 cm^{-1}). We introduce a new method to obtain reliable glucose absorption bands from aqueous glucose solutions without measuring the water displacement coefficients of glucose separately. Additionally, we are able to extract the water displacement coefficients of glucose, and this may give a new general method using spectroscopy techniques applicable to other water soluble materials. We also observe red shifts in the absorption bands of water in the hydration shell around solute molecules, which comes from contribution of the interacting water molecules around the glucose molecules in solutions. The intensity of the red shift get larger as the concentration increases, which indicates that as the concentration increases more water molecules are involved in the interaction. However, the red shift in frequency does not seem to depend significantly on the concentration up to our highest concentration. We also performed the same measurements and analysis with sucrose instead of glucose as solute and compare.

  9. Near-infrared studies of glucose and sucrose in aqueous solutions: water displacement effect and red shift in water absorption from water-solute interaction.

    PubMed

    Jung, Youngeui; Hwang, Jungseek

    2013-02-01

    We used near infrared spectroscopy to obtain concentration dependent glucose absorption spectra in aqueous solutions in the near-infrared range (3800-7500 cm(-1)). Here we introduce a new method to obtain reliable glucose absorption bands from aqueous glucose solutions without measuring the water displacement coefficients of glucose separately. Additionally, we were able to extract the water displacement coefficients of glucose, and this may offer a new general method using spectroscopy techniques applicable to other water-soluble materials. We also observed red shifts in the absorption bands of water in the hydration shell around solute molecules, which comes from the contribution of the interacting water molecules around the glucose molecules in solutions. The intensity of the red shift gets larger as the concentration increases, which indicates that as the concentration increases more water molecules are involved in the interaction. However, the red shift in frequency does not seem to depend significantly on the concentration. We also performed the same measurements and analysis with sucrose instead of glucose as solute and compared.

  10. Middle infrared, quantum cascade laser optoelectronic absorption system for monitoring glucose in serum.

    PubMed

    Martin, W Blake; Mirov, Sergey; Venugopalan, Ramakrishna

    2005-07-01

    Advances in middle infrared technology are leading researchers beyond the Fourier transform infrared spectrometer and to the quantum cascade laser. While most research focuses on gas-phase detection, recent research explores its use for condensed-phase matter studies. This work investigates its use for monitoring biologically relevant samples of glucose in serum. Samples with physiological glucose concentrations were monitored with a laser at 1036 cm-1. A 0.992 R2 linearity value was observed. In addition, using another laser at 1194 cm-1 as a measure of the background spectroscopic characteristics, a linearity of 0.998 R2 was observed. The average predictive standard errors of the mean (SEM) were 32.5 and 24.7 mg/dL, respectively, for each method. Quantum cascade lasers could be used to develop middle infrared devices for uses beyond the confines of the laboratory.

  11. Isotope concentrations from 24-h urine and 3-h serum samples can be used to measure intestinal magnesium absorption in postmenopausal women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a >/= 6-d stool or 3-d urine collection. We evaluated alternative meth...

  12. Ontogenic Changes of Villus Growth, Lactase Activity, and Intestinal Glucose Transporters in Preterm and Term Born Calves with or without Prolonged Colostrum Feeding.

    PubMed

    Steinhoff-Wagner, Julia; Schönhusen, Ulrike; Zitnan, Rudolf; Hudakova, Monika; Pfannkuche, Helga; Hammon, Harald M

    2015-01-01

    Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking.

  13. Ontogenic Changes of Villus Growth, Lactase Activity, and Intestinal Glucose Transporters in Preterm and Term Born Calves with or without Prolonged Colostrum Feeding

    PubMed Central

    Steinhoff-Wagner, Julia; Schönhusen, Ulrike; Zitnan, Rudolf; Hudakova, Monika; Pfannkuche, Helga; Hammon, Harald M.

    2015-01-01

    Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking. PMID:26011395

  14. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine.

    PubMed

    Frank, Daniel N; Bales, Elise S; Monks, Jenifer; Jackman, Matthew J; MacLean, Paul S; Ir, Diana; Robertson, Charles E; Orlicky, David J; McManaman, James L

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity.

  15. Perilipin-2 Modulates Lipid Absorption and Microbiome Responses in the Mouse Intestine

    PubMed Central

    Frank, Daniel N.; Bales, Elise S.; Monks, Jenifer; Jackman, Matthew J.; MacLean, Paul S.; Ir, Diana; Robertson, Charles E.; Orlicky, David J.; McManaman, James L.

    2015-01-01

    Obesity and its co-morbidities, such as fatty liver disease, are increasingly prevalent worldwide health problems. Intestinal microorganisms have emerged as critical factors linking diet to host physiology and metabolic function, particularly in the context of lipid homeostasis. We previously demonstrated that deletion of the cytoplasmic lipid drop (CLD) protein Perilipin-2 (Plin2) in mice largely abrogates long-term deleterious effects of a high fat (HF) diet. Here we test the hypotheses that Plin2 function impacts the earliest steps of HF diet-mediated pathogenesis as well as the dynamics of diet-associated changes in gut microbiome diversity and function. WT and perilipin-2 null mice raised on a standard chow diet were randomized to either low fat (LF) or HF diets. After four days, animals were assessed for changes in physiological (body weight, energy balance, and fecal triglyceride levels), histochemical (enterocyte CLD content), and fecal microbiome parameters. Plin2-null mice had significantly lower respiratory exchange ratios, diminished frequencies of enterocyte CLDs, and increased fecal triglyceride levels compared with WT mice. Microbiome analyses, employing both 16S rRNA profiling and metagenomic deep sequencing, indicated that dietary fat content and Plin2 genotype were significantly and independently associated with gut microbiome composition, diversity, and functional differences. These data demonstrate that Plin2 modulates rapid effects of diet on fecal lipid levels, enterocyte CLD contents, and fuel utilization properties of mice that correlate with structural and functional differences in their gut microbial communities. Collectively, the data provide evidence of Plin2 regulated intestinal lipid uptake, which contributes to rapid changes in the gut microbial communities implicated in diet-induced obesity. PMID:26147095

  16. Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA).

    PubMed

    Petit, Charlotte; Bujard, Alban; Skalicka-Woźniak, Krystyna; Cretton, Sylvian; Houriet, Joëlle; Christen, Philippe; Carrupt, Pierre-Alain; Wolfender, Jean-Luc

    2016-03-01

    At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high

  17. Effects of fasting on intestinal transfer of sugars and amino acids in vitro

    PubMed Central

    Newey, H.; Sanford, P. A.; Smyth, D. H.

    1970-01-01

    1. Transfer of sugars, amino acids and fluid and metabolism of glucose were studied with everted sacs of small intestine prepared from fed and 3-day fasted rats. 2. In the absence of glucose there was some evidence for increased intestinal transfer of sugars and amino acids in fasted animals. In the presence of glucose there was in general decrease in transfer of amino acids and fluid. 3. In fasted animals glucose transfer was reduced except in the lower ileum, and there was a general reduction in glucose metabolism. 4. Because of the large reduction in gut weight in fasted animals, expressing transfer on a weight basis is considered not to be a valid procedure in studying the effects of fasting on intestinal transfer. 5. The results have been discussed in relation to effects of fasting on energy availability, efficiency of transfer mechanisms, permeability of the intestine and the value of in vitro methods in the study of physiological absorption. PMID:5499792

  18. 25-Hydroxyvitamin D level does not reflect intestinal calcium absorption: an assay using strontium as a surrogate marker.

    PubMed

    Camargo, Marília Brasilio Rodrigues; Vilaça, Tatiane; Hayashi, Lilian Fukusima; Rocha, Olguita G Ferreira; Lazaretti-Castro, Marise

    2015-05-01

    There is conflicting evidence as to the optimal serum 25-hydroxyvitamin D [25(OH)D] concentration for intestinal calcium absorption (Abs-Ca). Our purpose was to assess the relationship between vitamin D status and Abs-Ca in postmenopausal women. Fifty volunteers with low bone mass were grouped according to their serum 25(OH)D concentration as follows: mild deficient, <50 nmol/L (DEF) and sufficient, ≥75 nmol/L (SUF). The subjects were submitted to an oral strontium overload test to assess their Abs-Ca. Fasting blood samples were obtained to perform the relevant hormonal and biochemical tests. After the subjects received the test solution, blood samples were drawn at 30, 60, 120, and 240 min to determine the strontium concentrations. Abs-Ca was indirectly expressed as the area under the serum strontium concentration curve (AUC). A repeated measures ANOVA was performed to determine the differences among the groups. Pearson's correlation and multiple linear regression analysis were used to study the associations between the variables. The mean 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations differed between the groups (SUF vs. DEF) as follows: 98.7 ± 18.2 vs. 38.4 ± 8.5 nmol/L (p < 0.001) and 36.2 ± 10.2 vs. 24.9 ± 4.6 pg/mL (p < 0.001), respectively. There was no statistically significant difference between the groups for parathyroid hormone and AUC. Only 1,25(OH)2D influenced the strontium absorption in the last 2 h of the test. In the studied population, no correlation between levels of 25(OH)D and Abs-Ca was found. Only 1,25(OH)2D influenced Abs-Ca as measured by a strontium absorption test.

  19. Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

    PubMed Central

    Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

    2006-01-01

    Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

  20. Effect of dietary fat on plasma glutathione peroxidase levels and intestinal absorption of /sup 75/Se-labeled sodium selenite in chicks

    SciTech Connect

    Mutanen, M.L.; Mykkaenen, H.M.

    1984-05-01

    The effect of dietary fat on the availability of selenium was investigated in chicks fed either 4 or 20% butter, olive oil, rape oil, corn oil or sunflower oil in the diet for 3 weeks after hatching. Plasma glutathione peroxidase (GSH-Px) activity was used as an indicator of the body selenium status. In addition, the intestinal absorption of sodium selenite (/sup 75/Se-labeled) was determined by using both the in vivo ligated loop procedure and oral administration of the isotope. The plasma GSH-Px levels increased with increasing proportion of the polyunsaturated fatty acids in the diet. Increasing the amount of fat from 4 to 20% significantly enhanced the GSH-Px activity in the groups receiving butter or olive oil, but had no effect in animals fed the unsaturated fats. The absorption of (/sup 75/Se)selenite from the ligated duodenal loops tended to be reduced in chicks fed corn oil or sunflower oil as compared to the animals receiving butter in their diet. On the other hand, the type of dietary fat did not appear to affect the absorption of the orally administered selenite. The present study demonstrates that the type of dietary fat can affect the plasma GSH-Px levels in chicks without altering the intestinal absorption of selenite. However, the results on the absorption of the intraduodenally injected sodium selenite suggest that dietary fat plays some role in the intestinal transport of selenium.

  1. The effect of different fatty acids on the intestinal lymphatic absorption of cyclosporin-A after oral administration in the rat

    SciTech Connect

    Jensen, B.K.

    1988-01-01

    Four studies were conducted in male Sprague-Dawley rats to evaluate the effect of saturated fatty acids (FA) of varying chain lengths on cyclosporin-A (CSA) intestinal lymphatic absorption. {sup 3}H-CSA was given to thoracic duct-ligated and sham rats in a nonlipid-(NL) or busyric (BA), octanoic (OA), lauric (LA), palmitic (PA), or stearic (SA) acid dosage form ({sup 14}C-FA) in an oral absorption study. The dosage forms were given to thoracic duct cannulated (TDC) rats to assess CSA intestinal lymphatic absorption. CSA blood-to-lymph transfer was assessed by intravenous {sup 3}H-CSA in TDC rats. Colchicine pretreated TDC rats received CSA in the NL and PA dosage forms. CSA and FA concentrations in blood and lymph were measured radiometrically. CSA and FA in the chylomicron and aqueous fractions were determined from ultracentrifugation of pooled lymph samples.

  2. Characteristics of reversible absorption-enhancing effect of sodium nitroprusside in rat small intestine.

    PubMed

    Takizawa, Yusuke; Kishimoto, Hisanao; Kitazato, Takuya; Ishizaka, Haruka; Kamiya, Naomi; Ito, Yasuhiko; Tomita, Mikio; Hayashi, Masahiro

    2013-07-16

    Nitric oxide (NO) donors increase the permeability of water-soluble compounds with neither loss of cell viability nor lactate dehydrogenase release. In addition, the rectal absorption of insulin has been reported to be remarkably enhanced in the presence of NO donors such as 1-Hydroxy-3-(3-aminopropyl)-3-isopropyltriazene 2-oxide (NOC5) and N-Ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC12). In this study, we examined the effect of sodium nitroprusside (SNP), which is used in clinical situations as a vasodilator, as a model NO donor on the ileal mucosa of rats. We used an in situ closed loop method in rat ileum to study changes in the permeability of fluorescein isothiocyanate dextran 4000 (FD-4) as a paracellular marker. The effect of SNP (1 and 10mg/kg) on the protein expression level of the claudin family was examined by Western blotting. The membrane permeation of FD-4 was increased but no mucosal lesion was observed upon the administration of SNP. Moreover, the protein expression level of the claudin family was not changed by the administration of SNP. When SNP was removed 2h after its administration, no significant change in the membrane permeation of FD-4 was observed. Moreover, no decrease of ileal membrane resistance or disruption of membrane structure was observed. The absorption-enhancing effect of SNP was associated with low injury and low toxicity. The reversibility of the effect of SNP was observed. Consequently, it was shown that SNP can be a useful absorption enhancer.

  3. Viscosity-mediated negative food effect on oral absorption of poorly-permeable drugs with an absorption window in the proximal intestine: In vitro experimental simulation and computational verification.

    PubMed

    Cvijić, Sandra; Parojčić, Jelena; Langguth, Peter

    2014-09-30

    Concomitant food intake can diminish oral absorption of drugs with limited permeability and an absorption window in the proximal intestine, due to viscosity-mediated decrease in dosage form disintegration time and drug dissolution rate. Three poorly-permeable drugs (atenolol, metformin hydrochloride, and furosemide) exhibiting negative food effect, and one highly-soluble and highly-permeable (metoprolol tartrate), serving as a negative control, were selected for the study. In vitro and in silico tools were used to evaluate the influence of media viscosity on drug bioperformance under fasted and fed conditions. The obtained results demonstrated that increased medium viscosity in the presence of food is one of the key factors limiting oral absorption of drugs with limited permeability and absorption restricted to the upper parts of the intestine, while having negligible effect on pharmacokinetic profile of drugs with pH- and site-independent absorption. Dissolution medium pH 4.6 with the addition of hydroxypropyl methylcellulose was suggested to simulate postprandial gastric conditions for drugs whose solubility under these conditions is not the limiting factor for drug absorption. In addition, drug formulation was found to be an interfering factor in relation to the impact of medium viscosity on the rate and extent of drug absorption.

  4. The Effects of Boron Derivatives on Lipid Absorption from the Intestine and on Bile Lipids and Bile Acids of Sprague Dawley Rats

    PubMed Central

    Hall, Iris H.; Reynolds, David J.; Wong, O. T.; Sood, A.; Spielvogel, B. F.

    1995-01-01

    N,N-dimethyl-n-octadecylamine borane 1 at 8 mg/kg/day, tetrakis-u-(trimethylamine boranecarboxylato)-bis(trimethyl-carboxyborane)-dicopper(II) 2 at 2.5 mg/kg/day and trimethylamine-carboxyborane 3 at 8 mg/kg/day were evaluated for their effects on bile lipids, bile acids, small intestinal absorption of cholesterol and cholic acid and liver and small intestinal enzyme activities involved in lipid metabolism. The agent administered orally elevated rat bile excretion of lipids, e.g. cholesterol and phospholipids, and compounds 2 and 3 increased the bile flow rate. These agents altered the composition of the bile acids, but there was no significant increase in lithocholic acid which is most lithogenic agent in rats. The three agents did decrease cholesterol absorption from isolated in situ intestinal duodenum loops in the presence of drug. Hepatic and small intestinal mucosa enzyme activities, e.g. ATP-dependent citrate lyase, acyl CoA cholesterol acyl transferase, cholsterol-7-α -hydroxylase, sn glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and lipoprotein lipase, were reduced. However, the boron derivatives 1 and 3 decreased hepatic HMG-CoA reductase activity, the regulatory enzyme for cholesterol synthesis, but the compounds had no effects on small intestinal mucosa HMG-CoA reductase activity. There was no evidence of hepatic cell damage afforded by the drugs based on clinical chemistry values which would induce alterations in bile acid concentrations after treatment of the rat. PMID:18472747

  5. Effects of steroids and sex reversal on intestinal absorption of L-(/sup 14/C)leucine in vivo, in rainbow trout, Salmo gairdneri

    SciTech Connect

    Habibi, H.R.; Ince, B.W.

    1983-12-01

    The effects of steroids (17 alpha-methyltestosterone (MT), 17 beta-oestradiol (E2)), and of sex reversal (XX male) on intestinal absorption and accumulation of L-(/sup 14/C)leucine (5 mM), were investigated in unanaesthetized rainbow trout (Salmo gairdneri), using an in vivo gut perfusion technique. Each steroid was luminally perfused through the gut at a concentration of 50 micrograms/ml perfusate, during five separate perfusions carried out on the same fish at 30-min intervals (perfusion periods 1 to 5), for a total of 120 min at 14 degrees. Experiments were also conducted on masculinized, genetically female trout (XX male) with steroid-free perfusate. MT treatment significantly increased the intestinal absorption of radioleucine during periods 1 and 2, whilst E2 was without effect. Neither MT nor E2 influenced intestinal accumulation (mid- and hindgut) of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. Sex reversal, however, whilst having no effect on leucine absorption, nevertheless significantly increased intestinal accumulation of radioleucine, and accumulation of /sup 14/C-solutes in skeletal muscle. The effects observed in the present study are in agreement with previous work in trout using everted gut sac preparations. It is suggested that the growth-promoting effects of anabolic-androgenic steroids in fish may be partly explained by their action on gastrointestinal function.

  6. Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine.

    PubMed

    Madsen, Jan L; Sjögreen-Gleisner, Katarina; Elema, Dennis R; Søndergaard, Lasse R; Rasmussen, Palle; Fuglsang, Stefan; Ljungberg, Michael; Damgaard, Morten

    2014-02-01

    Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [⁷⁵Se]L-SeMet ([⁷⁵Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [⁷⁵Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3)% of the administered activity of [⁷⁵Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1)% of the activity. Time-activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

  7. Effect of compounds affecting ABCA1 expression and CETP activity on the HDL pathway involved in intestinal absorption of lutein and zeaxanthin.

    PubMed

    Niesor, Eric J; Chaput, Evelyne; Mary, Jean-Luc; Staempfli, Andreas; Topp, Andreas; Stauffer, Andrea; Wang, Haiyan; Durrwell, Alexandre

    2014-12-01

    The antioxidant xanthophylls lutein and zeaxanthin are absorbed from the diet in a process involving lipoprotein formation. Selective mechanisms exist for their intestinal uptake and tissue-selective distribution, but these are poorly understood. We investigated the role of high-density lipoprotein (HDL), apolipoprotein (apo) A1 and ATP-binding cassette transporter (ABC) A1 in intestinal uptake of lutein in a human polarized intestinal cell culture and a hamster model. Animals received dietary lutein and zeaxanthin and either a liver X receptor (LXR) agonist or statin, which up- or down-regulate intestinal ABCA1 expression, respectively. The role of HDL was studied following treatment with the cholesteryl ester transfer protein (CETP) modulator dalcetrapib or the CETP inhibitor anacetrapib. In vitro, intestinal ABCA1 at the basolateral surface of enterocytes transferred lutein and zeaxanthin to apoA1, not to mature HDL. In hamsters, plasma lutein and zeaxanthin levels were markedly increased with the LXR agonist and decreased with simvastatin. Dalcetrapib, but not anacetrapib, increased plasma and liver lutein and zeaxanthin levels. ABCA1 expression and apoA1 acceptor activity are important initial steps in intestinal uptake and maintenance of lutein and zeaxanthin levels by an HDL-dependent pathway. Their absorption may be improved by physiological and pharmacological interventions affecting HDL metabolism.

  8. Nano-sized water-in-oil-in-water emulsion enhances intestinal absorption of calcein, a high solubility and low permeability compound.

    PubMed

    Koga, Kenjiro; Takarada, Nobuo; Takada, Kanji

    2010-02-01

    Our goal was to develop safe and stable multilayer emulsions capable of enhancing intestinal absorption of biopharmaceutics classification system (BCS) class III drugs. First, w/o emulsions were prepared using calcein as a model BCS class III compound and condensed ricinoleic acid tetraglycerin ester as a hydrophobic emulsifier. Then water-in-oil-in-water (w/o/w) emulsions were prepared with shirasu porous glass (SPG) membranes. Particle size analyses and calcein leakage from oil droplets in w/o/w emulsions led us to select stearic acid hexaglycerin esters (HS-11) and Gelucire 44/14 as hydrophilic emulsifiers. Analyses of the absorption-enhancing effects of w/o/w emulsions on intestinal calcein absorption in rats showed that calcein bioavailability after intraduodenal (i.d.) administration of HS-11 or Gelucire 44/14+polyvinyl alcohol (PVA) w/o/w emulsions prepared with 0.1-microm pore-sized SPGs was significantly higher than that of the calcein control. However, serum calcein concentration vs. time profiles after i.d. administration of w/o/w emulsions prepared with 1.1-microm and 30-microm pore-sized SPGs and an emulsion prepared with a calcein-containing outer water phase were comparable to control profiles. These results suggested that HS-11 or Gelucire 44/14+PVA are safe outer water phase additives and that 0.1-microm pore-sized SPGs are important for preparing w/o/w emulsions that enhanced intestinal calcein absorption.

  9. Influence of intoxication with vanadium compounds on the intestinal absorption of calcium in the rat

    SciTech Connect

    Witkowska, D.; Oledzka, R.; Pietrzyk, B.

    1986-12-01

    Calcium is transferred to the plasma after absorption from the gastrointestinal tract and by resorption from the bone. It is recognized that many environmental poisons, e.g. heavy metal, pesticides etc. cause alterations in calcium homeosthasis in human beings and experimental animals. Although vanadium is not considered to be as important a health hazard to man as lead or cadmium it must be nevertheless regarded as a dangerous pollutant. There exists an obvious risk of pollution by and poisoning due to the high vanadium content of crude oil and the industrial use of vanadium as a steel additive. The toxic effects of this element and its compounds in many biological systems have been reviewed in detail but little is known about vanadium influence on calcium metabolism. The present study was undertaken to determine the effect of various treatments with vanadium compounds, containing vanadium as VO/sup 2 +/ (VOSO/sub 4/) and VO/sub 3/ (NaVO/sub 3/) ions, exert on calcium transport through the rat duodenum.

  10. Enhancing the intestinal absorption of molecules containing the polar guanidino functionality: a double-targeted prodrug approach

    PubMed Central

    Sun, Jing; Dahan, Arik; Amidon, Gordon L.

    2011-01-01

    A prodrug strategy was applied to guanidino-containing analogs to increase oral absorption via hPEPT1 and hVACVase. L-Valine, L-isoleucine and L-phenylalanine esters of [3-(hydroxymethyl)phenyl]guanidine (3-HPG) were synthesized and evaluated for transport and activation. In HeLa/hPEPT1 cells, Val-3-HPG and Ile-3-HPG exhibited high affinity to hPEPT1 (IC50: 0.65 and 0.63 mM, respectively), and all three L-amino acid esters showed higher uptake (2.6- to 9-fold) than the parent compound 3-HPG. Val-3-HPG and Ile-3-HPG demonstrated remarkable Caco-2 permeability enhancement, and Val-3-HPG exhibited comparable permeability to valacyclovir. In rat perfusion studies, Val-3-HPG and Ile-3-HPG permeabilities were significantly higher than 3-HPG, and exceeded/matched the high-permeability standard metoprolol, respectively. All the L-amino acid 3-HPG esters were effectively activated in HeLa and Caco-2 cell homogenates, and were found to be good substrates of hVACVase (kcat/Km in mM−1·s−1: Val-3-HPG, 3370; Ile-3-HPG, 1580; Phe-3-HPG, 1660). In conclusion, a prodrug strategy is effective at increasing the intestinal permeability of polar guanidino analogs via targeting hPEPT1 for transport and hVACVase for activation. PMID:19957998

  11. In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

    PubMed

    López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

    2016-06-15

    Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer.

  12. In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

    PubMed

    López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

    2016-06-15

    Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer. PMID:27191052

  13. Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake.

    PubMed Central

    Berglund, M; Akesson, A; Nermell, B; Vahter, M

    1994-01-01

    Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. Figure 3. A Figure 3. B Figure 4. Figure 5. PMID:7713018

  14. Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

    PubMed

    Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

    2015-01-01

    We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

  15. Selenium (Se) deficiency alters intestinal diaphorase activity in mice infected with the intestinal parasitic worm Heligmosomoides polygyrus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mice fed a diet deficient in Se show reduced resistance to a secondary infection with H. polygyrus. IL-4 and IL-13-dependent- increases in intestinal smooth muscle hyper-contractility and decreased glucose absorption correlate with expulsion of the adult worm following a challenge infection. Selen...

  16. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    PubMed

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  17. [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

    PubMed

    Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

    2015-08-01

    This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract. PMID:26677717

  18. [Traditional Chinese medicine pairs (III)--effect of extract of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix on intestinal absorption in rats].

    PubMed

    Chen, Yi-hang; Li, Meng-xuan; Meng, Zhao-qing; Yang, Jiao-jiao; Huang, Wen-zhe; Wang, Zhen-zhong; Wang, Yue-sheng; Xiao, Wei

    2015-08-01

    This study focused on the intestinal absorption of traditional Chinese medicines (TCM) to reveal the scientific connotation of the compatibility of TCM pairs. The single pass intestinal perfusion (SPIP) was used in rats to compare the absorption of single extracts from Puerariae Lobatae Radix, single extracts from Ginseng Radix et Rhizoma, combined extracts from Puerariae Lobatae Radix and Ginseng Radix et Rhizoma and Puerariae Lobatae Radix and Ginseng Radix et Rhizoma mixture in rats. The content of puerarin, ginsenoside Rg1, ginsenoside Re and ginsenoside Rb1 in liquid were tested by HPLC. The speed constant (Ka) and apparent permeability coefficients (Papp) were calculated and compared. Specifically, the order of puerarin Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Puerariae Lobatae Radix > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix; the order of ginsenosides Ka and Papp values from high to low was Ginseng Radix et Rhizoma and Puerariae Lobatae Radix mixture > single extracts from Ginseng Radix et Rhizoma > combined extracts from Ginseng Radix et Rhizoma and Puerariae Lobatae Radix. The combined administration of Ginseng Radix et Rhizoma and Puerariae Lobatae Radix may improve the absorption in the intestinal tract.

  19. Investigation of the effects of soluble fibers on the absorption of resveratrol and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) in the Caco-2 cellular model of intestinal absorption.

    PubMed

    Willenberg, Ina; Wonik, Jasmin; Schebb, Nils Helge

    2015-01-01

    Soluble fibers are known to modulate intestinal absorption of non-polar compounds in the small intestine. Little is known about the modulation of absorption of more polar compounds. In the present study, we applied the Caco-2-transwell-system in order to investigate the modulation of intestinal bioavailability by soluble fibers. The system was tested using pectin and carrageenan as model soluble fibers at a concentration of 0.1% (w/v), which did not compromise the integrity of the cell monolayer. Modulation of absorption was evaluated for the heterocyclic amine aromatic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PHIP) and the polyphenol resveratrol. Neither pectin nor carrageenan reduced the high flux of PHIP, apparent permeability coefficient (Papp) of 16 × 10(-6) cm s(-1). The low Papp of resveratrol was reduced by both soluble fibers, particularly by pectin. These results suggest that the low bioavailability of polyphenols could be further reduced by soluble fibers. Because of their co-occurrence in several fruits, these findings warrant further research.

  20. Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.

    PubMed

    Wernstedt Asterholm, Ingrid; Kim-Muller, Ja Young; Rutkowski, Joseph M; Crewe, Clair; Tao, Caroline; Scherer, Philipp E

    2016-09-01

    Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype. PMID:27397737

  1. Lgr5 positive stem cells sorted from small intestines of diabetic mice differentiate into higher proportion of absorptive cells and Paneth cells in vitro.

    PubMed

    Zhong, Xian-Yang; Yu, Tao; Zhong, Wa; Li, Jie-Yao; Xia, Zhong-Sheng; Yuan, Yu-Hong; Yu, Zhong; Chen, Qi-Kui

    2015-08-01

    Intestinal epithelial stem cells (IESCs) can differentiate into all types of intestinal epithelial cells (IECs) and Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a marker for IESC. Previous studies reported enhanced proliferation of IECs in diabetic mice. In this study, the in vitro differentiation of Lgr5 positive IESCs sorted from diabetic mice was further investigated. The diabetic mouse model was induced by streptozotocin (STZ), and crypt IECs were isolated from small intestines. Subsequently, Lgr5 positive IESCs were detected by flow cytometry (FCM) and sorted by magnetic activated cell sorting (MACS). Differentiation of the sorted IESCs was investigated by detecting the IEC markers in the diabetic mice using immunostaining, quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), and Western blot analysis, which was compared with normal mice. We found that the proportion of Lgr5 positive cells in the crypt IECs of diabetic mice was higher than that of control mice (P < 0.05). Lgr5 positive IESCs could be significantly enriched in Lgr5 positive cell fraction sorted by MACS. Furthermore, the absorptive cell marker sucrase-isomaltase (SI) and the Paneth cell marker lysozyme 1 (Lyz1) were more highly expressed in the differentiated cells derived from Lgr5 positive IESCs of diabetic mice in vitro (P < 0.05). We demonstrate that the number of Lgr5 positive IESCs is significantly increased in the small intestines of STZ-induced diabetic mice. Lgr5 positive IESCs sorted from the diabetic mice can differentiate into a higher proportion of absorptive cells and Paneth cells in vitro. We characterized the expression of Lgr5 in the small intestine of diabetic mice, and sorted Lgr5 positive intestinal epithelial stem cells (IESCs) for investigating their differentiation in vitro. We proved that the quantity of Lgr5 positive IESCs was significantly increased in the small intestines of diabetic mice. IESCs sorted from the

  2. Sodium/glucose cotransporter-1, sweet receptor, and disaccharidase expression in the intestine of the domestic dog and cat: two species of different dietary habit.

    PubMed

    Batchelor, D J; Al-Rammahi, M; Moran, A W; Brand, J G; Li, X; Haskins, M; German, A J; Shirazi-Beechey, S P

    2011-01-01

    The domestic cat (Felis catus), a carnivore, naturally eats a very low carbohydrate diet. In contrast, the dog (Canis familiaris), a carno-omnivore, has a varied diet. This study was performed to determine the expression of the intestinal brush border membrane sodium/glucose cotransporter, SGLT1, sweet receptor, T1R2/T1R3, and disaccharidases in these species adapted to contrasting diets. The expression (this includes function) of SGLT1, sucrase, maltase and lactase were determined using purified brush border membrane vesicles and by quantitative immunohistochemistry of fixed tissues. The pattern of expression of subunits of the sweet receptor T1R2 and T1R3 was assessed using fluorescent immunohistochemistry. In proximal, middle, and distal small intestine, SGLT1 function in dogs was 1.9- to 2.3-fold higher than in cats (P = 0.037, P = 0.0011, P = 0.027, respectively), and SGLT1 protein abundance followed an identical pattern. Both cats and dogs express T1R3 in a subset of intestinal epithelial cells, and dogs, but not cats, express T1R2. In proximal and middle regions, there were 3.1- and 1.6-fold higher lactase (P = 0.006 and P = 0.019), 4.4- and 2.9-fold higher sucrase (both P < 0.0001), and 4.6- and 3.1-fold higher maltase activity (P = 0.0026 and P = 0.0005), respectively, in the intestine of dogs compared with cats. Dogs have a potential higher capacity to digest and absorb carbohydrates than cats. Cats may suffer from carbohydrate malabsorption following ingestion of high-carbohydrate meals. However, dogs have a digestive ability to cope with diets containing significant levels of carbohydrate.

  3. Large intestine (colon) (image)

    MedlinePlus

    ... portion of the digestive system most responsible for absorption of water from the indigestible residue of food. The ileocecal valve of the ileum (small intestine) passes material into the large intestine at the ...

  4. Intestinal absorption and blood clearance of L-histidine-related compounds after ingestion of anserine in humans and comparison to anserine-containing diets.

    PubMed

    Kubomura, Daiki; Matahira, Yoshiharu; Masui, Ayano; Matsuda, Hideki

    2009-03-11

    Anserine is a bioactive dipeptide found in muscles and brains of vertebrates, but little is known about the kinetics of its absorption into blood and the clearance after the ingestion of anserine or anserine-containing diets. This study investigated time-dependent changes in the concentrations of l-histidine-related compounds from deproteinized blood. The concentration of anserine peaked and then decreased to zero, whereas the concentration of pi-methylhistidine gradually increased, at which point anserine was not detected. Thus, ingested anserine is absorbed intact in human blood and is hydrolyzed to pi-methylhistidine and beta-alanine by serum and tissue carnosinases. Moreover, the crossover study suggests that there was no significant difference in absorption under curves of anserine between anserine alone and anserine-containing diet, whereas there was significant difference in the peak concentration of anserine. This is the first study to demonstrate intestinal absorption and blood clearance of anserine. PMID:19256552

  5. Increased calcium absorption in prehypertensive spontaneously hypertensive rat. Role of serum 1,25-dihydroxyvitamin D3 levels and intestinal brush border membrane fluidity.

    PubMed Central

    Lau, K; Langman, C B; Gafter, U; Dudeja, P K; Brasitus, T A

    1986-01-01

    Changes in Ca absorption have been described in the spontaneously hypertensive rat (SHR) compared with Wistar-Kyoto (WKy) rats. In 3.5-wk-old SHR and age-matched WKy controls, we measured direct arterial blood pressure, Ca absorption, and serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels and small intestine brush border membrane (BBM) fluidity and lipid composition. The two objectives were (a) to define the nature of the absorptive changes before detectable hypertension and (b) to evaluate the potential mechanism(s). We found that even at this normotensive stage (106 +/- 4 vs. 107 +/- 2 torr for the female and 109 +/- 3 vs. 104 +/- 3 torr for the male), the SHR (a) absorbed more Ca (1.46 +/- 0.06 vs. 1.14 +/- 0.08 mmol/d and 1.53 +/- 0.06 vs. 1.28 +/- 0.06 mmol/d, respectively) and retained more Ca, (b) had higher serum 1,25(OH)2D3 levels (340 +/- 36 vs. 160 +/- 18 pg/ml and 230 +/- 25 vs. 150 +/- 16 pg/ml, respectively), and (c) possessed BBM with increased fluidity and with reduced fatty acyl saturation index owing to decreased stearic (32.2 +/- 2.6% vs. 38.2 +/- 0.9%) but increased linoleic acids (12.2 +/- 2.0% vs. 7.6 +/- 1.6%). These results demonstrate increased Ca absorption in prehypertensive SHR associated with increased serum 1,25(OH)2D3 levels, increased intestinal BBM fluidity, and reduced saturation index, which singly or in combination could produce the changes in intestinal Ca transport. PMID:3760184

  6. Intestinal absorption mechanism of mirabegron, a potent and selective β₃-adrenoceptor agonist: involvement of human efflux and/or influx transport systems.

    PubMed

    Takusagawa, Shin; Ushigome, Fumihiko; Nemoto, Hiroyuki; Takahashi, Yutaka; Li, Qun; Kerbusch, Virginie; Miyashita, Aiji; Iwatsubo, Takafumi; Usui, Takashi

    2013-05-01

    Mirabegron, a weak-basic compound, is a potent and selective β3-adrenoceptor agonist for the treatment of overactive bladder. Mirabegron extended release formulation shows dose-dependent oral bioavailability in humans, which is likely attributable to saturation of intestinal efflux abilities leading to higher absorption with higher doses. This study evaluated the membrane permeability of mirabegron and investigated the involvement of human intestinal transport proteins in the membrane permeation of mirabegron. Transcellular transport and cellular/vesicular uptake assays were performed using Caco-2 cells and/or human intestinal efflux (P-glycoprotein [P-gp], breast cancer resistance protein [BCRP], and multidrug resistance associated protein 2 [MRP2]) and influx (peptide transporter 1 [PEPT1], OATP1A2, and OATP2B1) transporter-expressing cells, vesicles, or Xenopus laevis oocytes. The absorptive permeability coefficients of mirabegron in Caco-2 cells (1.68-1.83 × 10(-6) cm/s) at the apical and basal pH of 6.5 and 7.4, respectively, were slightly higher than those of nadolol (0.97-1.41 × 10(-6) cm/s), a low permeability reference standard, but lower than those of metoprolol and propranolol (both ranged from 8.49 to 11.6 × 10(-6) cm/s), low/high permeability boundary reference standards. Increasing buffer pH at the apical side from 5.5 to 8.0 gradually increased the absorptive permeation of mirabegron from 0.226 to 1.66 × 10(-6) cm/s, but was still less than the value in the opposite direction (11.0-14.2 × 10(-6) cm/s). The time- and concentration-dependent transport of mirabegron was observed in P-gp-expressing cells and OATP1A2-expressing oocytes with apparent Km values of 294 and 8.59 μM, respectively. In contrast, no clear BCRP-, MRP2-, PEPT1-, or OATP2B1-mediated uptake of mirabegron was observed in their expressing vesicles or cells. These findings suggest that mirabegron has low-to-moderate membrane permeability and P-gp is likely to be involved in its

  7. The 2',4',6'-trihydroxyacetophenone isolated from Myrcia multiflora has antiobesity and mixed hypolipidemic effects with the reduction of lipid intestinal absorption.

    PubMed

    Ferreira, Eduardo Antonio; Gris, Eliana Fortes; Rebello, Jussara Matos; Correia, João Francisco; de Oliveira, Luis Flávio; Filho, Danilo Wilhelm; Pedrosa, Rozangela Curi

    2011-09-01

    This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2',4',6'-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG-CoA reductase inhibitor or orlistat (26 and 34 %), a gastrointestinal lipase inhibitor. In addition, in the chronic assay with a high-fat diet, THA reduced cholesterol and triglyceride levels (32 and 61 %, respectively) while lovastatin showed a decrease of 35 and 49 %, respectively. THA also caused a reduction in weight gain very similar to orlistat (40 and 38 %, respectively) when the animals were submitted to a high-fat diet. Moreover, THA showed a stronger and continuous pancreatic lipase inhibitory activity when compared with orlistat, causing inhibition of this enzyme during 6 hours associated to a significant reduction of triglyceride serum levels. The IN VIVO antiobesity and hypolipidemic effects of THA may be partly mediated by delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity. PMID:21472649

  8. Mechanisms of calcium absorption by anterior and posterior segments of the intestinal tract of juvenile lake sturgeon.

    PubMed

    Genz, Janet; Carriere, Benjamin; Anderson, W Gary

    2013-10-01

    Rapid growth in juvenile fish increases calcium demand, and the intestine may play a role in calcium homeostasis at this life stage, in addition to branchial and renal transport. This study examined calcium flux in the gastrointestinal tract (GIT) of freshwater juvenile lake sturgeon acclimated to 0.14, 0.34, and 2.26mmol L(-1) environmental calcium. Net Ca(2+) flux did not differ due to environmental [Ca(2+)] in either the anterior or posterior intestine. Blocking the apical epithelial calcium channel (ECaC) with ruthenium red (RR, 8.5μmol L(-1)) significantly decreased Ca(2+) influx in the anterior intestine, but exposure to the plasma membrane Ca(2+)-ATP-ase (PMCA) inhibitor trifluoperazine (TFP, 10mmol L(-1)) had no effect at any environmental [Ca(2+)], nor did inhibition of the Na(+)-Ca(2+) exchanger (NCX) with KB-R7943 (10μmol L(-1)). Neither RR nor TFP affected Ca(2+) uptake by the posterior intestine in any of the treatment groups, but KB-R7943 reduced net calcium flux in the posterior intestine at all environmental [Ca(2+)]. Thus, basolateral Ca(2+) influx in the posterior GIT of lake sturgeon relies more heavily on NCX than PMCA. Furthermore, the differing pharmacological effects in the anterior and posterior intestine suggest that the dominant transporters responsible for calcium uptake vary over the length of the GIT in lake sturgeon.

  9. The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium.

    PubMed

    Ognik, Katarzyna; Stępniowska, Anna; Cholewińska, Ewelina; Kozłowski, Krzysztof

    2016-09-01

    Copper nanoparticles used as a dietary supplement for poultry could affect the absorption of mineral elements. Hence the aim of the study was to determine the effect of administration of copper nanoparticles to chickens in drinking water on intestinal absorption of iron, zinc, and calcium. The experiment was carried out on 126 chicks assigned to seven experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive copper nanoparticles. Groups: Cu-5(7), Cu-10(7), and Cu-15(7) received gold nanoparticles in their drinking water in the amounts of 5 mg/L for group Cu-5(7), 10 mg/L for group Cu-10(7), and 15 mg/L for group Cu-15(7) during 8 to 14, 22 to 28, and 36 of 42 days of the life of the chicks. The birds in groups Cu-5(3), Cu-10(3), and Cu-15(3) received copper nanoparticles in the same amounts, but only during 8 to 10, 22 to 24, and 36 to 38 days of life. Blood for analysis was collected from the wing vein of all chicks at the age of 42 days. After the rearing period (day 42), six birds from each experimental group with body weight similar to the group average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. Oral administration of copper nanoparticles to chickens in the amount of 5, 10, and 15 mg/L led to accumulation of this element in the intestinal walls. The highest level of copper nanoparticles applied increased Cu content in the blood plasma of the birds. The in vitro study suggests that copper accumulated in the intestines reduces absorption of calcium and zinc, but does not affect iron absorption. PMID:27307476

  10. Circadian regulation of intestinal lipid absorption by apolipoprotein AIV involves forkhead transcription factors A2 and O1 and microsomal triglyceride transfer protein.

    PubMed

    Pan, Xiaoyue; Munshi, Mohamed Khalid; Iqbal, Jahangir; Queiroz, Joyce; Sirwi, Alaa Ahmed; Shah, Shrenik; Younus, Abdullah; Hussain, M Mahmood

    2013-07-12

    We have shown previously that Clock, microsomal triglyceride transfer protein (MTP), and nocturnin are involved in the circadian regulation of intestinal lipid absorption. Here, we clarified the role of apolipoprotein AIV (apoAIV) in the diurnal regulation of plasma lipids and intestinal lipid absorption in mice. Plasma triglyceride in apoAIV(-/-) mice showed diurnal variations similar to apoAIV(+/+) mice; however, the increases in plasma triglyceride at night were significantly lower in these mice. ApoAIV(-/-) mice absorbed fewer lipids at night and showed blunted response to daytime feeding. To explain reasons for these lower responses, we measured MTP expression; intestinal MTP was low at night, and its induction after food entrainment was less in apoAIV(-/-) mice. Conversely, apoAIV overexpression increased MTP mRNA in hepatoma cells, indicating transcriptional regulation. Mechanistic studies revealed that sequences between -204/-775 bp in the MTP promoter respond to apoAIV and that apoAIV enhances expression of FoxA2 and FoxO1 transcription factors and their binding to the identified cis elements in the MTP promoter at night. Knockdown of FoxA2 and FoxO1 abolished apoAIV-mediated MTP induction. Similarly, knockdown of apoAIV in differentiated Caco-2 cells reduced MTP, FoxA2, and FoxO1 mRNA levels, cellular MTP activity, and media apoB. Moreover, FoxA2 and FoxO1 expression showed diurnal variations, and their expression was significantly lower in apoAIV(-/-) mice. These data indicate that apoAIV modulates diurnal changes in lipid absorption by regulating forkhead transcription factors and MTP and that inhibition of apoAIV expression might reduce plasma lipids.

  11. Hypolipidemic Effect of a Blue-Green Alga (Nostoc commune) Is Attributed to Its Nonlipid Fraction by Decreasing Intestinal Cholesterol Absorption in C57BL/6J Mice.

    PubMed

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Weller, Curtis L; Carr, Timothy P; Park, Young-Ki; Lee, Ji-Young

    2015-11-01

    We previously demonstrated that Nostoc commune var. sphaeroids Kützing (NO), a blue-green alga (BGA), exerts a hypolipidemic effect in vivo and its lipid extract regulates the expression of genes involved in cholesterol and lipid metabolism in vitro. The objective of this study was to investigate whether the hypolipidemic effect of NO is attributed to an algal lipid or a delipidated fraction in vivo compared with Spirulina platensis (SP). Male C57BL/6J mice were fed an AIN-93M diet containing 2.5% or 5% of BGA (w/w) or a lipid extract equivalent to 5% of BGA for 4 weeks to measure plasma and liver lipids, hepatic gene expression, intestinal cholesterol absorption, and fecal sterol excretion. Plasma total cholesterol (TC) was significantly lower in 2.5% and 5% NO-fed groups, while plasma triglyceride (TG) levels were decreased in the 5% NO group compared with controls. However, neither NO organic extract (NOE) nor SP-fed groups altered plasma lipids. Hepatic mRNA levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), carnitine palmitoyltransferase-1α, and acyl-CoA oxidase 1 were induced in 5% NO-fed mice, while there were no significant changes in hepatic lipogenic gene expression between groups. NO, but not NOE and SP groups, significantly decreased intestinal cholesterol absorption. When HepG2 cells and primary mouse hepatocytes were incubated with NOE and SP organic extract (SPE), there were marked decreases in protein levels of HMGR, low-density lipoprotein receptor, and fatty acid synthase. In conclusion, the nonlipid fraction of NO exerts TC and TG-lowering effects primarily by inhibiting intestinal cholesterol absorption and by increasing hepatic fatty acid oxidation, respectively. PMID:26161942

  12. Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice.

    PubMed

    Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R; Petersen, Max C; Nasiri, Ali; Butrico, Gina M; Abulizi, Abudukadier; Harmon, Daniel B; Lu, Canying; Mantell, Benjamin S; Hartman, Douglas J; Camporez, João-Paulo G; O'Doherty, Robert M; Cline, Gary W; Shulman, Gerald I; Jurczak, Michael J

    2016-07-01

    Mitochondrial dysfunction is associated with many human diseases and results from mismatch of damage and repair over the life of the organelle. PARK2 is a ubiquitin E3 ligase that regulates mitophagy, a repair mechanism that selectively degrades damaged mitochondria. Deletion of PARK2 in multiple in vivo models results in susceptibility to stress-induced mitochondrial and cellular dysfunction. Surprisingly, Park2 knockout (KO) mice are protected from nutritional stress and do not develop obesity, hepatic steatosis or insulin resistance when fed a high-fat diet (HFD). However, these phenomena are casually related and the physiological basis for this phenotype is unknown. We therefore undertook a series of acute HFD studies to more completely understand the physiology of Park2 KO during nutritional stress. We find that intestinal lipid absorption is impaired in Park2 KO mice as evidenced by increased fecal lipids and reduced plasma triglycerides after intragastric fat challenge. Park2 KO mice developed hepatic steatosis in response to intravenous lipid infusion as well as during incubation of primary hepatocytes with fatty acids, suggesting that hepatic protection from nutritional stress was secondary to changes in energy balance due to altered intestinal triglyceride absorption. Park2 KO mice showed reduced adiposity after 1-wk HFD, as well as improved hepatic and peripheral insulin sensitivity. These studies suggest that changes in intestinal lipid absorption may play a primary role in protection from nutritional stress in Park2 KO mice by preventing HFD-induced weight gain and highlight the need for tissue-specific models to address the role of PARK2 during metabolic stress. PMID:27166280

  13. [Comparative studies on the enzymatic absorption of protein hydrolysates in the small intestine of the rat. 3. The absorption trypsins thermatatic and trypsin-thermatatic hydrolysates of a fava bean protein isolate compared to an equimolar mixture of free amino acids].

    PubMed

    Proll, J; Friedrich, M; Noack, J; Noack, R

    1985-01-01

    Tryptic, thermitatic, and tryptic-thermitatic Faba bean protein hydrolyzates as well as their equimolar mixture of amino acids were perfused through proximal and distal parts of the intestine (10 cm length) of non-narcotized rats. The total amino-acid concentration of the perfused solution was 50 mM. The absorption of nitrogen and total amino acids from the tryptic and tryptic-thermitatic hydrolyzates was lower than that from the amino-acid mixture, the absorption from the thermitatic hydrolyzate was in accordance with that from the amino-acid mixture. The absorption pattern of the amino acids which preferably undergo a peptidic absorption is similar with the three hydrolyzates: in the proximal intestinal part this concerns glutamic acid and serine, in the distal intestinal part--methionine, alanine, glycin, and serine. The absorption pattern of the amino acids is different between the three hydrolyzates and the amino-acid mixture. Between the absorption pattern of the amino acids from the three hydrolyzates little differences were evident only in the proximal intestinal part. The coefficients of variation of the tryptic-thermitatic hydrolyzates are in accordance with those of the amino-acid mixture, whereas that of the thermitatic hydrolyzates is significantly lower. In the distal intestinal part all supplied forms are more rapidly absorbed than in the proximal part of the intestine.

  14. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    PubMed

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard.

  15. [Carbohydrate absorption and malabsorption (author's transl)].

    PubMed

    Caspary, W F

    1977-06-01

    Starch is digested intraluminally by alpha-amylase to maltose, maltotriose, and alpha-limit dextrins. These products, as well as the disaccharides sucrose and lactose, undergo enzymatic hydrolysis to monosaccharides at the brush border surface. The monosaccharides enter the absorbing cell by specific transport mechanisms ("carriers"). Primary carbohydrate (CH) intolerance is characterized by the congenital or acquired absence of individual brush border enzymes or of monosaccharide "carriers" without morphologic abnormalities of the intestinal villus: lactose, sucrose and trehalose intolerance and glucose-galactose malabsorption (brush border diseases). Secondary CH intolerance arises when surface digestion and absorption are reduced due to structural changes of the intestinal mucosa: e.g., decrease or absence of villi with sprue and reduction of the absorbing surface with intestinal resection. Watery diarrhea is the lead symptom. Many drugs delay or interfere with CH absorption. This action may be viewed either as an unwanted side effect or as a welcome therapeutic principle.

  16. Effect of colchicine on rat small intestinal absorptive cells. II. Distribution of label after incorporation of (/sup 3/H)fucose into plasma membrane glycoproteins

    SciTech Connect

    Ellinger, A.; Pavelka, M.; Gangl, A.

    1983-12-01

    By means of radioautography the influence was tested of various periods (5, 15, 30, 40 min, 2 hr) of pretreatment with colchicine, administered intraperitoneally to rats at a dosage of 0.5 mg/100 g of body weight, on the intracellular pathway of (/sup 3/H)fucose in absorptive cells of the small intestine. Administration of colchicine for 30 min and longer time intervals causes delay in the insertion of (/sup 3/H)fucose into the oligosaccharide chains of glycoconjugates in the Golgi apparatus, and results in redistribution of the label apparent over the different portions of the plasma membrane. In controls, at 2 and 4 hr after administration of (/sup 3/H)fucose the apical plasma membrane is strongly labeled. Colchicine causes equalization of the reaction of apical and basolateral regions of the plasma membrane: the number of silver grains attributable to the apical plasma membrane is reduced; following treatment with colchicine, apical portions of the plasma membrane comprise 31.6 +/- 1.8% of the silver grains, 38.6 +/- 3.8% are attributable to basolateral membrane regions. The colchicine-induced equalization of the density of label of apical and basolateral regions of the plasma membrane, in addition to the occurrence of basolateral microvillus borders, suggests microtubules to be important in the maintenance of the polar organization of small intestinal absorptive cells.

  17. Comparison of a Computer Simulation Program and a Traditional Laboratory Practical Class for Teaching the Principles of Intestinal Absorption.

    ERIC Educational Resources Information Center

    Dewhurst, D. G.; And Others

    1994-01-01

    Evaluates the effectiveness of an interactive computer-assisted learning program for undergraduate students that simulates experiments performed using isolated, everted sacs of rat small intestine. The program is designed to offer an alternative student-centered approach to traditional laboratory-based practical classes. Knowledge gain of students…

  18. Coassimilation of dietary fat and benzo(a)pyrene in the small intestine: an absorption model using the killifish

    SciTech Connect

    Vetter, R.D.; Carey, M.C.; Patton, J.S.

    1985-04-01

    Benzo(a)pyrene (BP) was dissolved in dietary fat and fed in a single dose to killifish (Fundulus heteroclitus). Fluorescence microscopic examinations of small intestinal content and frozen sections of whole small intestine revealed that during fat digestion BP was codispersed in liquid crystalline product phases produced during lipolysis and then coabsorbed with dietary lipid followed by its reappearance in intracellular fat droplets. During the time that the absorbed fat remained in the enterocytes, BP fluorescence was initially concentrated in the intracellular fat droplets and then spread throughout the cytosol of the enterocytes. Tissue analyses showed that BP was rapidly metabolized in the intestine and transported to the gallbladder. These studies show that separation of a dissolved hydrophobic carcinogen from dietary fat occurs primarily after the fat has been digested, dispersed, absorbed, and reassembled in the enterocyte. The inability of the enterocyte to discriminate between dietary fat and dissolved carcinogenic compounds may be a partial explanation of the observed link between high fat diets and the incidence of some cancers. In vertebrates, the intestine and not the liver, appears to be the major site of metabolism of dietary polycyclic aromatic hydrocarbons (PAHs).

  19. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    PubMed

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates.

  20. Cholesterol esterification by ACAT2 is essential for efficient intestinal cholesterol absorption: evidence from thoracic lymph duct cannulation[S

    PubMed Central

    Nguyen, Tam M.; Sawyer, Janet K.; Kelley, Kathryn L.; Davis, Matthew A.; Rudel, Lawrence L.

    2012-01-01

    The hypothesis tested in this study was that cholesterol esterification by ACAT2 would increase cholesterol absorption efficiency by providing cholesteryl ester (CE) for incorporation into chylomicrons. The assumption was that absorption would be proportional to Acat2 gene dosage. Male ACAT2+/+, ACAT2+/−, and ACAT2−/− mice were fed a diet containing 20% of energy as palm oil with 0.2% (w/w) cholesterol. Cholesterol absorption efficiency was measured by fecal dual-isotope and thoracic lymph duct cannulation (TLDC) methods using [3H]sitosterol and [14C]cholesterol tracers. Excellent agreement among individual mice was found for cholesterol absorption measured by both techniques. Cholesterol absorption efficiency in ACAT2−/− mice was 16% compared with 46–47% in ACAT2+/+ and ACAT2+/− mice. Chylomicrons from ACAT2+/+ and ACAT2+/− mice carried ∼80% of total sterol mass as CE, whereas ACAT2−/− chylomicrons carried >90% of sterol mass in the unesterified form. The total percentage of chylomicron mass as CE was reduced from 12% in the presence of ACAT2 to ∼1% in ACAT2−/− mice. Altogether, the data demonstrate that ACAT2 increases cholesterol absorption efficiency by providing CE for chylomicron transport, but one copy of the Acat2 gene, providing ∼50% of ACAT2 mRNA and enzyme activity, was as effective as two copies in promoting cholesterol absorption. PMID:22045928

  1. A high retinol dietary intake increases its apical absorption by the proximal small intestine of juvenile sunshine bass (Morone chrysops x M. saxatilis).

    PubMed

    Buddington, Randal K; Buddington, Karyl K; Deng, Dong-Fang; Hemre, Gro-Ingunn; Wilson, Robert P

    2002-09-01

    The relationship between dietary intake and systemic availability of retinol is likely to be complex because although retinol is an essential nutrient, it is toxic at high levels. The present study determined whether rates of transapical retinol absorption are modulated so that availability is increased at low dietary levels, but decreased when dietary intake is excessive. Juvenile hybrid striped bass were fed for 6 wk diets with 568 (below), 1657 (approximating the requirement) and 40,244 (excessive) micro g/kg dry diet of trans retinol. Proximal small intestine segments were used to measure rates of retinol absorption and tissue concentrations. Initial and final body mass did not differ among groups; deficiency and toxicity symptoms were not observed. Uptake of tracer retinol was inhibited by unlabeled retinol, indicating the presence of saturable, carrier-mediated absorption. Increasing dietary levels of retinol increased the rates of absorption measured at 0.05 mmol/L [8.04 +/- 0.65; 15.2 +/- 1.53; 25.1 +/- 3.4 pmol/(mg. min) for below, approximating and exceeding the retinol requirement; P < 0.0001]; this resulted in higher tissue concentrations of all-trans retinol (0.21 +/- 0.03, 0.49 +/- 0.21 and 338 +/- 89 pmol/g; P < 0.0001) and dehydro-retinol (0.11 +/- 0.04, 0.91 +/- 0.04, and 454 +/- 109 pmol/g; P < 0.001). These findings suggest that the systemic availability of various dietary levels of retinol is modulated after transapical absorption.