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Sample records for intestinal glucose absorption

  1. 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

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

    PubMed Central

    Chen, Lihong; Tuo, Biguang; Dong, Hui

    2016-01-01

    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 ([Ca2+]cyt) can regulate the absorption of glucose by adjusting GLUT2 and SGLT1. Moreover, the absorption of glucose and homeostasis of Ca2+ in IEC are regulated by cation channels and transporters, such as Ca2+ channels, K+ channels, Na+/Ca2+ 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. PMID:26784222

  3. Inhibitory effect of Ipomoea aquatica extracts on glucose absorption using a perfused rat intestinal preparation.

    PubMed

    Sokeng, S D; Rokeya, B; Hannan, J M A; Junaida, K; Zitech, P; Ali, L; Ngounou, G; Lontsi, D; Kamtchouing, P

    2007-12-01

    Investigations were carried out to evaluate the effect of Ipomoea aquatica aqueous and dichloromethane/methanol extracts on the glucose absorption using a rat intestinal preparation in situ. Extracts orally tested at the dose of 160 mg/kg exerted a significant inhibitory effect on glucose absorption when compared with control animals. The most pronounced effect was observed with the aqueous extract. Ouabain used as reference inhibitor strongly inhibited glucose absorption. On the other hand both plant extracts inhibited the gastrointestinal motility suggesting that the inhibition of glucose absorption is not due to the acceleration of intestinal transit. PMID:17651914

  4. 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. PMID:25656339

  5. Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

    PubMed

    Daumerie, C; Henquin, J C

    1982-03-01

    The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars. PMID:6284563

  6. 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. PMID:25108868

  7. 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. PMID:26487007

  8. 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

  9. Disordered Control of Intestinal Sweet Taste Receptor Expression and Glucose Absorption in Type 2 Diabetes

    PubMed Central

    Young, Richard L.; Chia, Bridgette; Isaacs, Nicole J.; Ma, Jing; Khoo, Joan; Wu, Tongzhi; Horowitz, Michael; Rayner, Christopher K.

    2013-01-01

    We previously established that the intestinal sweet taste receptors (STRs), T1R2 and T1R3, were expressed in distinct epithelial cells in the human proximal intestine and that their transcript levels varied with glycemic status in patients with type 2 diabetes. Here we determined whether STR expression was 1) acutely regulated by changes in luminal and systemic glucose levels, 2) disordered in type 2 diabetes, and 3) linked to glucose absorption. Fourteen healthy subjects and 13 patients with type 2 diabetes were studied twice, at euglycemia (5.2 ± 0.2 mmol/L) or hyperglycemia (12.3 ± 0.2 mmol/L). Endoscopic biopsy specimens were collected from the duodenum at baseline and after a 30-min intraduodenal glucose infusion of 30 g/150 mL water plus 3 g 3-O-methylglucose (3-OMG). STR transcripts were quantified by RT-PCR, and plasma was assayed for 3-OMG concentration. Intestinal STR transcript levels at baseline were unaffected by acute variations in glycemia in healthy subjects and in type 2 diabetic patients. T1R2 transcript levels increased after luminal glucose infusion in both groups during euglycemia (+5.8 × 104 and +5.8 × 104 copies, respectively) but decreased in healthy subjects during hyperglycemia (−1.4 × 104 copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 × 105 copies). Plasma 3-OMG concentrations were significantly higher in type 2 diabetic patients than in healthy control subjects during acute hyperglycemia. Intestinal T1R2 expression is reciprocally regulated by luminal glucose in health according to glycemic status but is disordered in type 2 diabetes during acute hyperglycemia. This defect may enhance glucose absorption in type 2 diabetic patients and exacerbate postprandial hyperglycemia. PMID:23761104

  10. Role of villus microcirculation in intestinal absorption of glucose: coupling of epithelial with endothelial transport

    PubMed Central

    Pappenheimer, J R; Michel, C C

    2003-01-01

    Capillaries in jejunal villi can absorb nutrients at rates several hundred times greater (per gram tissue) than capillaries in other tissues, including contracting skeletal muscle and brain. We here present an integrative hypothesis to account for these exceptionally large trans-endothelial fluxes and their relation to epithelial transport. Equations are developed for estimating concentration gradients of glucose across villus capillary walls, along paracellular channels and across subjunctional lateral membranes of absorptive cells. High concentrations of glucose discharged across lateral membranes to subjunctional intercellular spaces are delivered to abluminal surfaces of villus capillaries by convection-diffusion in intercellular channels without significant loss of concentration. Post-junctional paracellular transport thus provides the series link between epithelial and endothelial transport and makes possible the large trans-endothelial concentration gradients required for absorption to blood. Our analysis demonstrates that increases of villus capillary blood flow and permeability-surface area product (PS) are essential components of absorptive mechanisms: epithelial transport of normal digestive loads could not be sustained without concomitant increases in capillary blood flow and PS. The low rates of intestinal absorption found in anaesthetised animals may be attributed to inhibition of normal villus microvascular responses to epithelial transport. PMID:12937296

  11. 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

  12. Dependence of intestinal glucose absorption on sodium, studied with a new arterial infusion technique

    PubMed Central

    Fisher, R. B.; Gardner, M. L. G.

    1974-01-01

    1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated. 2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974). 3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled. 4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion. 5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline. 6. Ouabain (10-4 M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l. 7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone. 8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration. PMID:4422318

  13. Role of rat intestinal glucoamylase in glucose polymer hydrolysis and absorption.

    PubMed

    Azad, M A; Lebenthal, E

    1990-08-01

    Rice starch is a main source of energy in many lesser developed countries. We studied different chain-lengths of rice glucose polymers (GP) to evaluate their possible use in feeding infants in developing countries. The initial GP of rice (G1 = 4.6, G2 = 4.5, G3 = 15.4, G4 = 7.3, G5 = 17.4, G6-G9 = 9.61 and greater than G9 = 31.3%) was analyzed by HPLC and then separated in a Bio-Gel P-2 column and compared to its short-chain GP of rice (G2 = 22.7, G3 = 28.2, G4 = 14.0, G5 = 16.6, G6 = 11.6, G7-G9 = 6.9%), long-chain GP of rice (greater than G9 = 100%), and D-glucose. Intraduodenal bolus infusion of 10% solution of short-chain rice GP when compared with long-chain rice GP, the initial rice GP, or D-glucose showed significantly higher values at peak absorption time (0 to 30 min) in the portal venous blood glucose response. The portal venous glycemic response of short-chain rice GP compared with D-glucose was as follows: 2.5 +/- 0.1 versus 2.0 +/- 0.2 cm2, area under the portal blood glucose curve at 0-30 min (p less than 0.01). Glucoamylase, the key enzyme for brush-border hydrolysis of short-chain GP, was assessed with a newly modified glucoamylase assay using GP G5-G8 as substrate. Our finding of faster glucose absorption with short-chain rice GP compared with isocaloric D-glucose might have important physiologic implications for carbohydrate absorption. The osmolality of short-chain rice GP is nearly one-fourth that of glucose. This might have important bearing in the design of infant feeding where increased caloric density with low osmolality is desirable. PMID:2118618

  14. Endothelin-1 potently stimulates chloride secretion and inhibits Na(+)-glucose absorption in human intestine in vitro.

    PubMed Central

    Kuhn, M; Fuchs, M; Beck, F X; Martin, S; Jähne, J; Klempnauer, J; Kaever, V; Rechkemmer, G; Forssmann, W G

    1997-01-01

    1. Serosally added synthetic endothelin-1 (ET-1) increased short-circuit current (Isc) across isolated muscle-stripped human colonic mucosa in vitro. Bumetanide inhibited Isc responses, indicating that ET-1 stimulates electrogenic Cl- secretion. 2. In isolated human jejunal mucosa, ET-1 exhibited a concentration-dependent dual action. At low concentrations it induced rapid increases in Isc and these were inhibited by bumetanide. At a higher concentration (0.1 microM), ET-1 provoked a drastic and progressive decrease in Isc below the baseline value. 3. Pretreatment with phlorizin or omission of glucose from the Krebs-Ringer solution at the apical (luminal) side of the jejunal mucosa prevented the decreases in Isc evoked by ET-1, suggesting that the peptide inhibits the glucose-coupled electrogenic Na+ absorption. Indeed, flux experiments with D-[14C]glucose demonstrated that ET-1 decreases jejunal glucose absorption by approximately 80% within 30 min. 4. Electron microprobe analyses of cryosections of human jejunum showed that ET-1 (0.1 microM) evokes a significant decrease in intracellular Na+ concentrations of villus (not crypt) epithelial cells, suggesting that the peptide attenuates apical Na(+)-glucose entry by reducing the activity of the Na(+)-glucose cotransporter, SGLT1. 5. In the presence of tetrodotoxin (TTX), ET-1-induced Cl- secretion was significantly reduced, in both human jejunal and colonic mucosa. However, the inhibitory effect on jejunal Na(+)-glucose absorption was not affected by TTX. 6. ET-1 increases electrogenic Cl- secretion across human intestinal mucosa in vitro. This effect is mediated in part via the activation of enteric nerves. Responses of the human jejunal mucosa to high ET-1 concentrations exhibit a second component, namely the rapid inhibition of electrogenic Na(+)-glucose absorption, which might be mediated by an inhibition of the transport activity of SGLT1. This effect is independent from neuronal mediators. Our results suggest

  15. Aqueous extracts of husks of Plantago ovata reduce hyperglycaemia in type 1 and type 2 diabetes by inhibition of intestinal glucose absorption.

    PubMed

    Hannan, J M A; Ali, L; Khaleque, J; Akhter, M; Flatt, P R; Abdel-Wahab, Y H A

    2006-07-01

    Plantago ovata has been reported to reduce postprandial glucose concentrations in diabetic patients. In the present study, the efficacy and possible modes of action of hot-water extracts of husk of P. ovata were evaluated. The administration of P. ovata (0.5 g/kg body weight) significantly improved glucose tolerance in normal, type 1 and type 2 diabetic rat models. When the extract was administered orally with sucrose solution, it suppressed postprandial blood glucose and retarded small intestinal absorption without inducing the influx of sucrose into the large intestine. The extract significantly reduced glucose absorption in the gut during in situ perfusion of small intestine in non-diabetic rats. In 28 d chronic feeding studies in type 2 diabetic rat models, the extract reduced serum atherogenic lipids and NEFA but had no effect on plasma insulin and total antioxidant status. No effect of the extract was evident on intestinal disaccharidase activity. Furthermore, the extract did not stimulate insulin secretion in perfused rat pancreas, isolated rat islets or clonal beta cells. Neither did the extract affect glucose transport in 3T3 adipocytes. In conclusion, aqueous extracts of P. ovata reduce hyperglycaemia in diabetes via inhibition of intestinal glucose absorption and enhancement of motility. These attributes indicate that P. ovata may be a useful source of active components to provide new opportunities for diabetes therapy. PMID:16870001

  16. 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.

  17. Intestinal folate absorption

    PubMed Central

    Strum, Williamson; Nixon, Peter F.; Bertino, Joseph B.; Binder, Henry J.

    1971-01-01

    Intestinal absorption of the monoglutamate form of the principal dietary and circulating folate compound, 5-methyltetrahydrofolic acid (5-MTHF), was studied in the rat utilizing a synthetic highly purified radiolabeled diastereoisomer. Chromatography confirmed that the compound was not altered after transfer from the mucosa to the serosa. Accumulation against a concentration gradient was not observed in duodenal, jejunal, or ileal segments at 5-MTHF concentration from 0.5 to 500 nmoles/liter. Unidirectional transmural flux determination also did not indicate a significant net flux. Mucosal to serosal transfer of 5-MTHF was similar in all segments of the intestine and increased in a linear fashion with increased initial mucosal concentrations. Further, no alteration in 5-MTHF transfer was found when studied in the presence of metabolic inhibitors or folate compounds. These results indicate that 5-MTHF is not absorbed by the rat small intestine by a carrier-mediated system and suggest that 5-MTHF transfer most likely represents diffusion. Images PMID:5564397

  18. The Intestinal Absorption of Folates

    PubMed Central

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I. David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

  19. The intestinal absorption of folates.

    PubMed

    Visentin, Michele; Diop-Bove, Ndeye; Zhao, Rongbao; Goldman, I David

    2014-01-01

    The properties of intestinal folate absorption were documented decades ago. However, it was only recently that the proton-coupled folate transporter (PCFT) was identified and its critical role in folate transport across the apical brush-border membrane of the proximal small intestine established by the loss-of-function mutations identified in the PCFT gene in subjects with hereditary folate malabsorption and, more recently, by the Pcft-null mouse. This article reviews the current understanding of the properties of PCFT-mediated transport and how they differ from those of the reduced folate carrier. Other processes that contribute to the transport of folates across the enterocyte, along with the contribution of the enterohepatic circulation, are considered. Important unresolved issues are addressed, including the mechanism of intestinal folate absorption in the absence of PCFT and regulation of PCFT gene expression. The impact of a variety of ions, organic molecules, and drugs on PCFT-mediated folate transport is described. PMID:24512081

  20. 1-deoxynojirimycin inhibits glucose absorption and accelerates glucose metabolism in streptozotocin-induced diabetic mice

    PubMed Central

    Li, You-Gui; Ji, Dong-Feng; Zhong, Shi; Lin, Tian-Bao; Lv, Zhi-Qiang; Hu, Gui-Yan; Wang, Xin

    2013-01-01

    We investigated the role of 1-deoxynojirimycin (DNJ) on glucose absorption and metabolism in normal and diabetic mice. Oral and intravenous glucose tolerance tests and labeled 13C6-glucose uptake assays suggested that DNJ inhibited intestinal glucose absorption in intestine. We also showed that DNJ down-regulated intestinal SGLT1, Na+/K+-ATP and GLUT2 mRNA and protein expression. Pretreatment with DNJ (50 mg/kg) increased the activity, mRNA and protein levels of hepatic glycolysis enzymes (GK, PFK, PK, PDE1) and decreased the expression of gluconeogenesis enzymes (PEPCK, G-6-Pase). Assays of protein expression in hepatic cells and in vitro tests with purified enzymes indicated that the increased activity of glucose glycolysis enzymes was resulted from the relative increase in protein expression, rather than from direct enzyme activation. These results suggest that DNJ inhibits intestinal glucose absorption and accelerates hepatic glucose metabolism by directly regulating the expression of proteins involved in glucose transport systems, glycolysis and gluconeogenesis enzymes. PMID:23536174

  1. 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

  2. Effects of insulin-like growth factor-I and its analogue, long-R3-IGF-I, on intestinal absorption of 3-O-methyl-D-glucose are less pronounced than gut mucosal growth responses.

    PubMed

    Garnaut, Sonja M; Howarth, Gordon S; Read, Leanna C

    2002-03-01

    The relationship between insulin-like growth factor-I (IGF-I) peptide-induced increases in bowel mass and functional improvement is unclear. We utilised three independent methods to investigate the effects of IGF-I peptides on intestinal absorption of the glucose analogue, 3-O-methyl-D-glucose (3MG) in rats. Rats received vehicle, IGF-I or the more potent analogue, long-R3-IGF-I via subcutaneously implanted mini-pump, for 7 days, at which time intestinal absorption was assessed by: (1) plasma 3MG appearance following oral gavage, (2) single-pass- or (3) recirculating-perfusion of a jejunal segment. 3MG (320 or 800 mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R3-IGF-I. With the lower 3MG dose, only long-R3-IGF-I increased (40%) the initial rate of 3MG appearance in plasma. IGF-I had no significant effect, whilst at the higher 3MG dose neither peptide was effective. Utilising perfusion techniques, long-R3-IGF-I, but not IGF-I, significantly increased 3MG uptake per cm of jejunum by up to 69%, although significance was lost when expressed as a function of tissue weight. Long-R3-IGF-I, but not native IGF-I, enhanced 3MG absorption from the intestinal lumen, presumably reflecting an increased mucosal mass rather than an up-regulation of specific epithelial glucose transporters. PMID:11999215

  3. 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

  4. Nutrient absorption and intestinal adaptation with ageing.

    PubMed

    Woudstra, Trudy; Thomson, Alan B R

    2002-02-01

    Malabsorption of carbohydrates, lipids, amino acids, minerals and vitamins has been described in the elderly. The ability of the intestine to adapt may be impaired in the elderly and this may lead to further malnutrition. Dietary manipulation may prove to be useful to enhance the needed intestinal absorption with ageing. There is an age-associated increase in the prevalence of dyslipidaemia as well as diabetes. These conditions may benefit from nutritional intervention targeted at reducing the absorption of some nutrients. With the continued characterization of the proteins involved in sterol and fatty acid absorption, therapeutic interventions to modify absorption may become available in the future. PMID:11977925

  5. 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

  6. 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…

  7. Mechanisms of intestinal calcium absorption.

    PubMed

    Bronner, Felix

    2003-02-01

    Calcium is absorbed in the mammalian small intestine by two general mechanisms: a transcellular active transport process, located largely in the duodenum and upper jejunum; and a paracellular, passive process that functions throughout the length of the intestine. The transcellular process involves three major steps: entry across the brush border, mediated by a molecular structure termed CaT1, intracellular diffusion, mediated largely by the cytosolic calcium-binding protein (calbindinD(9k) or CaBP); and extrusion, mediated largely by the CaATPase. Chyme travels down the intestinal lumen in approximately 3 h, spending only minutes in the duodenum, but over 2 h in the distal half of the small intestine. When calcium intake is low, transcellular calcium transport accounts for a substantial fraction of the absorbed calcium. When calcium intake is high, transcellular transport accounts for only a minor portion of the absorbed calcium, because of the short sojourn time and because CaT1 and CaBP, both rate-limiting, are downregulated when calcium intake is high. Biosynthesis of CaBP is fully and CaT1 function is approximately 90% vitamin D-dependent. At high calcium intakes CaT1 and CaBP are downregulated because 1,25(OH)(2)D(3), the active vitamin D metabolite, is downregulated. PMID:12520541

  8. 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.

  9. 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

  10. 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

  11. Effects of dietary starch source on electrophysiological intestinal epithelial properties and intestinal glucose uptake in growing goats.

    PubMed

    Klinger, Stefanie; Zurich, Meike; Schröder, Bernd; Breves, Gerhard

    2013-08-01

    In ruminants, the potential benefit of by-pass starch to improve energy supply is under discussion. As efficient intestinal starch digestion and monosaccharide absorption are important prerequisites for an energetic benefit compared to ruminal fermentation, this study was conducted to characterise potential adaptations of intestinal tissues to different dietary starch sources qualitatively. The Ussing chamber technique was used to determine electrophysiological parameters of jejunal tissues and glucose flux rates. Kinetics of sodium-dependent glucose uptake into isolated brush-border membrane vesicles (BBMV) were calculated, and the expression level of sodium-dependent glucose transporter 1 (SGLT1) was determined. Samples were collected from goats that were assigned to three dietary treatments differing in starch content (hay/concentrate) and starch source (wheat/corn). Additionally, ingesta samples were analysed for starch and glucose contents. Jejunal tissues from hay-fed animals showed higher tissue conductances (G t) and numerically higher short-circuit currents (I sc). Unidirectional glucose flux rates were higher for hay-fed animals, whereas net flux rates were unaffected. The maximal glucose transport capacity into BBMV was increased for concentrate-fed animals, but the affinity and SGLT1 expression were not affected. Our results may indicate an adaptation of glucose uptake via SGLT1 to variations in dietary starch but it could not be excluded that intestinal uptake capacity was saturated under the given conditions or that the measured capacity was sufficient for absorption of available glucose. PMID:23879718

  12. Intestinal Absorption and Metabolism of Epimedium Flavonoids in Osteoporosis Rats.

    PubMed

    Zhou, Jing; Ma, Yi Hua; Zhou, Zhong; Chen, Yan; Wang, Ying; Gao, Xia

    2015-10-01

    Herba Epimdii is a traditional Chinese medicine used to treat osteoporosis. Its main pharmacological ingredients are flavonoids. In previous studies conducted in healthy animals, we showed that epimedium flavonoids could be hydrolyzed into secondary glycosides or aglycon by intestinal flora or enzymes, thereby enhancing their absorption and antiosteoporosis activity. To study the medicine in the pathologic state, epimedium flavonoids were incubated with intestinal mucosa and feces in vitro and intestinal perfusion in situ to explore the differences in absorption and metabolism between sham and osteoporosis rats. For osteoporosis rats, the hydrolysis rates of icariin, epimedin A, epimedin B, and epimedin C incubated with intestinal flora for 1 hour were reduced by 0.19, 0.26, 0.19, and 0.14, respectively, compared with that in sham rats. Hydrolysis rates were reduced by 0.21, 0.24, 0.08, and 0.31 for icariin, epimedin A, epimedin B, and epimedin C incubated with duodenal enzymes for 1 hour and by 0.13, 0.09, 0.07, and 0.47 for icariin, epimedin A, epimedin B, and epimedin C incubated with jejunum enzymes, respectively, compared with the sham group. In addition, the apparent permeability coefficient and elimination percentage of the four epimedium flavonoids in the duodenum, jejunum, ileum, and colon decreased by 29%-44%, 32%-50%, 40%-56%, and 27%-53% compared with that in sham rats, respectively. The main metabolites of the four epimedium flavonoids were the same for the two groups after intestinal perfusion, or flora and enzyme incubation. In conclusion, the amount and activity of intestinal flora and enzymes changed in ovariectomized rats, which affected the intestinal absorption and hydrolysis of epimedium flavonoids whose structures contain 7-glucose. PMID:26135008

  13. [Suppression of glucose absorption by various health teas in rats].

    PubMed

    Matsuura, Toshiki; Yoshikawa, Yukako; Masui, Hironori; Sano, Mitsuaki

    2004-04-01

    The inhibitory effects on the intestinal digestion and absorption of sugar of health teas that claim beneficial dietary and diabetes-controlling effects were compared in rats using portal cannulae. The measured durations were the times during which the elevation of portal glucose levels resulting from continuous intragastric infusion of sucrose or maltose was suppressed by concentrated teas. The teas investigated included salacia oblonga, mulberry, guava, gymunema, taheebo, yacon, and banaba. The duration of the inhibitory effect on the sucrose load of salacia oblonga, mulberry, and guava were 110 min, 20 min, and 10 min, respectively. In contrast, gymunema, taheebo, yacon, and banaba had no significant effect on the continuous infusion of sucrose. These results suggest that there is considerable difference in the efficacy of commercial health teas in influencing glucose absorption. PMID:15067185

  14. 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

  15. 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

  16. 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

  17. Intestinal Lipid Absorption and Lipoprotein Formation

    PubMed Central

    Hussain, M. Mahmood

    2014-01-01

    Purpose of review The purpose of this review is to summarize evidence for the presence of two pathways of lipid absorption and their regulation. Recent findings Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine followed by the uptake of hydrolyzed products by enterocytes. Lipids are re-synthesized in the endoplasmic reticulum and are either secreted with chylomicrons and high density lipoproteins or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are critically dependent on MTP and ABCA1, respectively, and are regulated independently. Gene ablation studies showed that MTP function and chylomicron assembly is essential for the absorption of triglyceride and retinyl esters. Ablation of MTP abolishes triglyceride absorption and results in massive triglyceride accumulation in enterocytes. Although majority of phospholipid, cholesterol and vitamin E are absorbed through the chylomicron pathway, a significant amount of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and secretion is increased by the enhanced availability of fatty acids, whereas HDL pathway is upregulated by LXR agonists. Intestinal insulin resistance increases chylomicron and might reduce HDL production. Summary Triglycerides are exclusively transported via the chylomicron pathway and this process is critically dependent on MTP. Besides chylomicrons, absorption of phospholipids, free cholesterol, retinol, and vitamin E also involves high density lipoproteins. These two pathways are complementary and are regulated independently. They may be targeted to lower lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis and other disorders. PMID:24751933

  18. The digestive adaptation of flying vertebrates: High intestinal paracellular absorption compensates for smaller guts

    PubMed Central

    Caviedes-Vidal, Enrique; McWhorter, Todd J.; Lavin, Shana R.; Chediack, Juan G.; Tracy, Christopher R.; Karasov, William H.

    2007-01-01

    Anecdotal evidence suggests that birds have smaller intestines than mammals. In the present analysis, we show that small birds and bats have significantly shorter small intestines and less small intestine nominal (smooth bore tube) surface area than similarly sized nonflying mammals. The corresponding >50% reduction in intestinal volume and hence mass of digesta carried is advantageous because the energetic costs of flight increase with load carried. But, a central dilemma is how birds and bats satisfy relatively high energy needs with less absorptive surface area. Here, we further show that an enhanced paracellular pathway for intestinal absorption of water-soluble nutrients such as glucose and amino acids may compensate for reduced small intestines in volant vertebrates. The evidence is that l-rhamnose and other similarly sized, metabolically inert, nonactively transported monosaccharides are absorbed significantly more in small birds and bats than in nonflying mammals. To broaden our comparison and test the veracity of our finding we surveyed the literature for other similar studies of paracellular absorption. The patterns found in our focal species held up when we included other species surveyed in our analysis. Significantly greater amplification of digestive surface area by villi in small birds, also uncovered by our analysis, may provide one mechanistic explanation for the observation of higher paracellular absorption relative to nonflying mammals. It appears that reduced intestinal size and relatively enhanced intestinal paracellular absorption can be added to the suite of adaptations that have evolved in actively flying vertebrates. PMID:18025481

  19. The Glucagon-Like Peptide 1 Receptor Agonist Exenatide Inhibits Small Intestinal Motility, Flow, Transit, and Absorption of Glucose in Healthy Subjects and Patients With Type 2 Diabetes: A Randomized Controlled Trial.

    PubMed

    Thazhath, Sony S; Marathe, Chinmay S; Wu, Tongzhi; Chang, Jessica; Khoo, Joan; Kuo, Paul; Checklin, Helen L; Bound, Michelle J; Rigda, Rachael S; Crouch, Benjamin; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2016-01-01

    The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 μg) or saline (-30 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq (99m)Tc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia. PMID:26470783

  20. Defective intestinal amino acid absorption in Ace2 null mice.

    PubMed

    Singer, Dustin; Camargo, Simone M R; Ramadan, Tamara; Schäfer, Matthias; Mariotta, Luca; Herzog, Brigitte; Huggel, Katja; Wolfer, David; Werner, Sabine; Penninger, Josef M; Verrey, François

    2012-09-15

    Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations

  1. 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. PMID:25576062

  2. Foregut Exclusion Disrupts Intestinal Glucose Sensing and Alters Portal Nutrient and Hormonal Milieu

    PubMed Central

    Pal, Atanu; Rhoads, David B.

    2015-01-01

    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. PMID:25576062

  3. Mechanisms and regulation of intestinal iron absorption.

    PubMed

    Morgan, Evan H; Oates, Phillip S

    2002-01-01

    Iron absorption from the small intestine is regulated according to the body's needs, increasing in iron deficiency and decreasing in iron overload. It has been proposed that the efficiency of absorption is determined by the amount of iron acquired by developing enterocytes when they are in the crypts of Lieberkůhn and that this regulates expression of iron transporters such as DMT1 in mature enterocytes of the intestinal villi. In the crypts the cells take up iron from plasma transferrin by receptor-mediated endocytosis, a process that is influenced by the hemochromatosis protein, HFE. Hence, the availability of plasma transferrin-bound iron and the expression and function of transferrin receptors (TfR1), HFE and DMT1 should all contribute to the absorptive capacity of villus enterocytes. These aspects of the regulation and mechanism of iron absorption were investigated in genetically normal rats and mice, and in Belgrade anemic (b/b) rats and HFE knockout mice. In most experiments the function of the TfR1 was assessed by the uptake of radiolabeled transferrin-bound iron given intravenously. Absorption of non-heme iron was measured using closed in situ duodenal loops. The expression and cellular distribution of DMT1 and TfR1 were determined by in situ hybridisation and immunohistochemistry. The uptake of transferrin-bound iron and expression of functional TfR1 was shown to occur mainly in crypt cells and to be proportional to the plasma concentration of iron. It was not impaired by the mutation of DMT1 that occurs in b/b rats but was impaired in HFE knockout mice. Iron absorption was increased in these mice but was still influenced by the level of iron stores, as in normal mice. These results are in accordance with the proposed regulation of iron absorption and suggest that DMT1 is not the only iron transporter operating within endosomes of crypt cells. This view was supported by the failure to detect DMT1 mRNA or protein in crypt cells. Expression of DMT1 m

  4. Intestinal gluconeogenesis and glucose transport according to body fuel availability in rats

    PubMed Central

    Habold, Caroline; Foltzer-Jourdainne, Charlotte; Le Maho, Yvon; Lignot, Jean-Hervé; Oudart, Hugues

    2005-01-01

    Intestinal hexose absorption and gluconeogenesis have been studied in relation to refeeding after two different fasting phases: a long period of protein sparing during which energy expenditure is derived from lipid oxidation (phase II), and a later phase characterized by a rise in plasma corticosterone triggering protein catabolism (phase III). Such a switch in body fuel uses, leading to changes in body reserves and gluconeogenic precursors, could modulate intestinal gluconeogenesis and glucose transport. The gene and protein levels, and the cellular localization of the sodium–glucose cotransporter SGLT1, and of GLUT5 and GLUT2, as well as that of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (Glc6Pase) were measured. PEPCK and Glc6Pase activities were also determined. In phase III fasted rats, SGLT1 was up-regulated and intestinal glucose uptake rates were higher than in phase II fasted and fed rats. PEPCK and Glc6Pase mRNA, protein levels and activities also increased in phase III. GLUT5 and GLUT2 were down-regulated throughout the fast, but increased after refeeding, with GLUT2 recruited to the apical membrane. The increase in SGLT1 expression during phase III may allow glucose absorption at low concentrations as soon as food is available. Furthermore, an increased epithelial permeability due to fasting may induce a paracellular movement of glucose. In the absence of intestinal GLUT2 during fasting, Glc6Pase could be involved in glucose release to the bloodstream via membrane trafficking. Finally, refeeding triggered GLUT2 and GLUT5 synthesis and apical recruitment of GLUT2, to absorb larger amounts of hexoses. PMID:15878950

  5. 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

  6. Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes.

    PubMed

    Zuckerman, Marc J; Menzies, Ian S; Ho, Hoi; Gregory, Gavin G; Casner, Nancy A; Crane, Roger S; Hernandez, Jesus A

    2004-04-01

    Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects

  7. 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

  8. [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

  9. Bile Diversion in Roux-en-Y Gastric Bypass Modulates Sodium-Dependent Glucose Intestinal Uptake.

    PubMed

    Baud, Gregory; Daoudi, Mehdi; Hubert, Thomas; Raverdy, Violeta; Pigeyre, Marie; Hervieux, Erik; Devienne, Magalie; Ghunaim, Mohamed; Bonner, Caroline; Quenon, Audrey; Pigny, Pascal; Klein, André; Kerr-Conte, Julie; Gmyr, Valery; Caiazzo, Robert; Pattou, François

    2016-03-01

    Gastro-intestinal exclusion by Roux-en-Y gastric bypass (RYGB) improves glucose metabolism, independent of weight loss. Although changes in intestinal bile trafficking have been shown to play a role, the underlying mechanisms are unclear. We performed RYGB in minipigs and showed that the intestinal uptake of ingested glucose is blunted in the bile-deprived alimentary limb (AL). Glucose uptake in the AL was restored by the addition of bile, and this effect was abolished when active glucose intestinal transport was blocked with phlorizin. Sodium-glucose cotransporter 1 remained expressed in the AL, while intraluminal sodium content was markedly decreased. Adding sodium to the AL had the same effect as bile on glucose uptake. It also increased postprandial blood glucose response in conscious minipigs following RYGB. The decrease in intestinal uptake of glucose after RYGB was confirmed in humans. Our results demonstrate that bile diversion affects postprandial glucose metabolism by modulating sodium-glucose intestinal cotransport. PMID:26924216

  10. 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. PMID:24731596

  11. Tacrolimus Induces Insulin Resistance and Increases the Glucose Absorption in the Jejunum: A Potential Mechanism of the Diabetogenic Effects

    PubMed Central

    Zhang, Yaohui; Chen, Hao; He, Ningning; Chen, Hui; Song, Penghong; Wang, Yan; Yan, Sheng; Zheng, Shusen

    2015-01-01

    Background The use of the immunosuppressive drug tacrolimus (TAC) is related to new onset diabetes after transplantation. Herein, we examined the effect of intraperitoneal administered TAC on intestinal glucose absorption in mice. Methods Animals received low, medium, or high dose TAC (0.5, 1, or 5 mg/kg/d, respectively), or 0.9% saline solution (control) for 14 days. Oral glucose tolerance test (OGTT), insulin concentration test, and serum TAC concentration measurements was performed after 14 days of TAC exposure. Plasma insulin was assessed and electrogenic glucose absorption were measured by the sodium-dependent increase of the short-circuit current. Expression levels of the glucose transporters sodium glucose co-transporter (SGLT) 1, glucose transporter (GLUT) 2, and GLUT5 were also determined. Results Oral glucose absorption assessed by OGTT was significantly enhanced in the low, medium, and high groups. Serum insulin was elevated in the medium and high group compared with the control. Moreover, glucose-induced Isc was significantly higher in TAC administrated groups, which indicates that SGLT1 activity increased. Transcription levels and protein abundance of SGLT1 in the experimental groups also increased compared with the control. Conclusions TAC induced insulin resistance and strengthened intestinal glucose absorption by increasing the activity and expression of the glucose transporter, SGLT1. PMID:26599323

  12. 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. PMID:26256322

  13. Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man.

    PubMed Central

    Flourie, B; Vidon, N; Florent, C H; Bernier, J J

    1984-01-01

    The effect of high methoxy apple pectin, a carbohydrate gelling agent, on the intestinal absorption of glucose, water, and sodium was studied in man. The effect of intraluminal fibre was evaluated in 22 healthy volunteers by the intestinal perfusion technique under an occlusive balloon. The test solutions (NaCl 130 mM, KCl 5 mM, glucose or mannitol 30 mM, PEG 4000 5 g/l) were perfused just beyond the ligament of Treitz at a rate of 10 ml/min. A 25 cm segment was studied. Three concentrations of pectin were tested: 6, 10, and 15 g/l. The effect of this pectin at two concentrations, 6 and 10 g/l, on the jejunal unstirred layer thickness was evaluated in nine other healthy subjects by an electrical technique. In mannitol solution, pectin reversed water and sodium absorption, whatever its concentration was, while in glucose solution it significantly reduced absorption of water and sodium at 10 and 15 g/l only (p less than 0.01). It significantly reduced glucose absorption at all concentrations (p less than 0.01). This reduction was found to be correlated with the solution viscosity (p less than 0.01). Pectin did not alter the glucose dependent sodium transport but increased significantly (p less than 0.001) the unstirred layer thickness. These results suggested that, in healthy man, pectin acutely given may impair intestinal absorption by means of an increased unstirred layer resistance. This effect could contribute to the diminished postprandial glycaemia observed in human subjects fed pectin. PMID:6432635

  14. Effect of pectin on jejunal glucose absorption and unstirred layer thickness in normal man.

    PubMed

    Flourie, B; Vidon, N; Florent, C H; Bernier, J J

    1984-09-01

    The effect of high methoxy apple pectin, a carbohydrate gelling agent, on the intestinal absorption of glucose, water, and sodium was studied in man. The effect of intraluminal fibre was evaluated in 22 healthy volunteers by the intestinal perfusion technique under an occlusive balloon. The test solutions (NaCl 130 mM, KCl 5 mM, glucose or mannitol 30 mM, PEG 4000 5 g/l) were perfused just beyond the ligament of Treitz at a rate of 10 ml/min. A 25 cm segment was studied. Three concentrations of pectin were tested: 6, 10, and 15 g/l. The effect of this pectin at two concentrations, 6 and 10 g/l, on the jejunal unstirred layer thickness was evaluated in nine other healthy subjects by an electrical technique. In mannitol solution, pectin reversed water and sodium absorption, whatever its concentration was, while in glucose solution it significantly reduced absorption of water and sodium at 10 and 15 g/l only (p less than 0.01). It significantly reduced glucose absorption at all concentrations (p less than 0.01). This reduction was found to be correlated with the solution viscosity (p less than 0.01). Pectin did not alter the glucose dependent sodium transport but increased significantly (p less than 0.001) the unstirred layer thickness. These results suggested that, in healthy man, pectin acutely given may impair intestinal absorption by means of an increased unstirred layer resistance. This effect could contribute to the diminished postprandial glycaemia observed in human subjects fed pectin. PMID:6432635

  15. 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.

  16. 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.

  17. Reciprocal regulation of the primary sodium absorptive pathways in rat intestinal epithelial cells.

    PubMed

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit; Sundaram, Uma

    2011-03-01

    Sodium absorption in the mammalian small intestine occurs predominantly by two primary pathways that include Na/H exchange (NHE3) and Na-glucose cotransport (SGLT1) on the brush border membrane (BBM) of villus cells. However, whether NHE3 and SGLT1 function together to regulate intestinal sodium absorption is unknown. Nontransformed small intestinal epithelial cells (IEC-18) were transfected with either NHE3 or SGLT1 small interfering RNAs (siRNAs) and were grown in confluent monolayers on transwell plates to measure the effects on Na absorption. Uptake studies were performed as well as molecular studies to determine the effects on NHE3 and SGLT1 activity. When IEC-18 monolayers were transfected with silencing NHE3 RNA, the cells demonstrated decreased NHE3 activity as well as decreased NHE3 mRNA and protein. However, in NHE3 siRNA-transected cells, SGLT1 activity, mRNA, and protein in the BBM were significantly increased. Thus, inhibition of NHE3 expression regulates the expression and function of SGLT1 in the BBM of intestinal epithelial cells. In addition, IEC-18 cells transected with silencing SGLT1 RNA demonstrated an inhibition of Na-dependent glucose uptake and a decrease in SGLT1 activity, mRNA, and protein levels. However, in these cells, Na/H exchange activity was significantly increased. Furthermore, NHE3 mRNA and protein levels were also increased. Therefore, the inhibition of SGLT1 expression stimulates the transcription and function of NHE3 and vice versa in the BBM of intestinal epithelial cells. Thus this study demonstrates that the major sodium absorptive pathways together function to regulate sodium absorption in epithelial cells. PMID:21148403

  18. Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

    SciTech Connect

    Radziuk, J.; Bondy, D.C.

    1982-11-01

    The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with (1-/sup 14/C)glucose and measuring glucose clearance using plasma levels of infused (3-/sup 3/H)glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation. That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery.

  19. 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

  20. 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

  1. 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

  2. The effect of some beverage extracts on intestinal iron absorption.

    PubMed

    el-Shobaki, F A; Saleh, Z A; Saleh, N

    1990-12-01

    The effect of some beverage extracts namely anise, mint, caraway, cumin, tilia, liquorice, karkade and tea, on the absorption of iron was tested in tied-off intestinal segments of rats. The rate of intestinal iron absorption was calculated in terms of an absorption index. The tannin, phytic acid and ascorbic acid contents of these beverages were analysed. The results show that anise, mint, caraway, cumin, tilia, liquorice, arranged in decreasing order of their effect, promoted the absorption of iron. Karkade did not exert an appreciable effect while tea inhibited absorption. The results are discussed in relation to the content of these beverages of tannins, phytic or ascorbic acids. It is recommended to offer these beverages to children and also to adults as a preventive agent to iron deficiency anemia. Also can be used for the preparation of bioavailable medicinal iron. PMID:2080638

  3. Intestinal absorption of dolichol from emulsions and liposomes in rats.

    PubMed

    Kimura, T; Takeda, K; Kageyu, A; Toda, M; Kurosaki, Y; Nakayama, T

    1989-02-01

    The intestinal absorption of dolichol from various dosage forms was investigated using the intestinal loop and everted sac methods in the rat. The in situ loop experiments showed that the absorption of dolichol from a triglyceride emulsion was dependent on the chain-length of the triglyceride; the absorption from a tri-n-butyrin emulsion in 1 h was 18.0% of the dose; and the absorption from an HCO-60 suspension was 4.3%. The liposomal preparation enhanced the absorption up to 39.1% of the dose. In in vitro experiments, 25.0% and 13.2% of dolichol were taken up by everted sacs of the jejunum and the ileum, respectively. On the other hand, phospholipids composing liposomes were not absorbed under these conditions. The above results suggest that the absorption mechanism from liposomal preparations may be as follows: dolichol is released from the liposomes into the aqueous phase adjacent to the surface of the intestine and is subsequently partitioned into the intestinal tissue. PMID:2743494

  4. 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.

  5. The mechanisms of sodium absorption in the human small intestine

    PubMed Central

    Fordtran, John S.; Rector, Floyd C.; Carter, Norman W.

    1968-01-01

    The present studies were designed to characterize sodium transport in the jejunum and ileum of humans with respect to the effects of water flow, sodium concentration, addition of glucose and galactose, and variations in aniomic composition of luminal fluid. In the ileum, sodium absorption occurred against very steep electrochemical gradients (110 mEq/liter, 5-15 mv), was unaffected by the rate or direction of water flow, and was not stimulated by addition of glucose, galactose, or bicarbonate. These findings led to the conclusion that there is an efficiently active sodium transport across a membrane that is relatively impermeable to sodium. In contrast, jejunal sodium (chloride) absorption can take place against only the modest concentration gradient of 13 mEq/liter, was dramatically influenced by water movement, and was stimulated by addition of glucose, galactose, and bicarbonate. The stimulatory effect of glucose and galactose was evident even when net water movement was inhibited to zero by mannitol. These observations led to the conclusion that a small fraction of jejunal sodium absorption was mediated by active transport coupled either to active absorption of bicarbonate or active secretion of hydrogen ions. The major part of sodium absorption, i.e. sodium chloride absorption, appeared to be mediated by a process of bulk flow of solution along osmotic pressure gradients. The stimulatory effect of glucose and galactose, even at zero water flow, was explained by a model in which the active transport of monosaccharide generates a local osmotic force for the absorption of solution (NaCl and water) from the jejunal lumen, which, in the presence of mannitol, is counterbalanced by a reverse flow of pure solvent (H2O) through a parallel set of channels which are impermeable to sodium. Support for the model was obtained by the demonstration that glucose and bicarbonate stimulated the absorption of the nonactively transported solute urea even when net water flow was

  6. 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.

  7. Intestinal scavenger receptors are involved in vitamin K1 absorption.

    PubMed

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-10-31

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone. PMID:25228690

  8. Intestinal Scavenger Receptors Are Involved in Vitamin K1 Absorption*

    PubMed Central

    Goncalves, Aurélie; Margier, Marielle; Roi, Stéphanie; Collet, Xavier; Niot, Isabelle; Goupy, Pascale; Caris-Veyrat, Catherine; Reboul, Emmanuelle

    2014-01-01

    Vitamin K1 (phylloquinone) intestinal absorption is thought to be mediated by a carrier protein that still remains to be identified. Apical transport of vitamin K1 was examined using Caco-2 TC-7 cell monolayers as a model of human intestinal epithelium and in transfected HEK cells. Phylloquinone uptake was then measured ex vivo using mouse intestinal explants. Finally, vitamin K1 absorption was compared between wild-type mice and mice overexpressing scavenger receptor class B type I (SR-BI) in the intestine and mice deficient in cluster determinant 36 (CD36). Phylloquinone uptake by Caco-2 cells was saturable and was significantly impaired by co-incubation with α-tocopherol (and vice versa). Anti-human SR-BI antibodies and BLT1 (a chemical inhibitor of lipid transport via SR-BI) blocked up to 85% of vitamin K1 uptake. BLT1 also decreased phylloquinone apical efflux by ∼80%. Transfection of HEK cells with SR-BI and CD36 significantly enhanced vitamin K1 uptake, which was subsequently decreased by the addition of BLT1 or sulfo-N-succinimidyl oleate (CD36 inhibitor), respectively. Similar results were obtained in mouse intestinal explants. In vivo, the phylloquinone postprandial response was significantly higher, and the proximal intestine mucosa phylloquinone content 4 h after gavage was increased in mice overexpressing SR-BI compared with controls. Phylloquinone postprandial response was also significantly increased in CD36-deficient mice compared with wild-type mice, but their vitamin K1 intestinal content remained unchanged. Overall, the present data demonstrate for the first time that intestinal scavenger receptors participate in the absorption of dietary phylloquinone. PMID:25228690

  9. Recent developments in intestinal calcium absorption.

    PubMed

    Bronner, Felix

    2009-02-01

    Calcium absorption proceeds by transcellular and paracellular flux, with the latter accounting for most absorbed calcium when calcium intake is adequate. Vitamin D helps regulate transcellular calcium transport by increasing calcium uptake via a luminal calcium channel and by inducing the cytosolic calcium transporting protein, calbindinD(9k). Recent studies utilizing knockout mice have challenged the functional importance of the channel and calbindin. To integrate the new findings with many previous studies, the function of the two molecules must be evaluated in the calcium transport and economy of mice. When calcium intake is high, transcellular calcium transport contributes little to total calcium absorption. Therefore, increasing calcium intake seems the most effective nutritional approach to ensure adequate absorption and prevent bone loss. PMID:19178653

  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. PMID:25033063

  11. Intestinal Sodium Glucose Cotransporter 1 Inhibition Enhances Glucagon-Like Peptide-1 Secretion in Normal and Diabetic Rodents.

    PubMed

    Oguma, Takahiro; Nakayama, Keiko; Kuriyama, Chiaki; Matsushita, Yasuaki; Yoshida, Kumiko; Hikida, Kumiko; Obokata, Naoyuki; Tsuda-Tsukimoto, Minoru; Saito, Akira; Arakawa, Kenji; Ueta, Kiichiro; Shiotani, Masaharu

    2015-09-01

    The sodium glucose cotransporter (SGLT) 1 plays a major role in glucose absorption and incretin hormone release in the gastrointestinal tract; however, the impact of SGLT1 inhibition on plasma glucagon-like peptide-1 (GLP-1) levels in vivo is controversial. We analyzed the effects of SGLT1 inhibitors on GLP-1 secretion in normoglycemic and hyperglycemic rodents using phloridzin, CGMI [3-(4-cyclopropylphenylmethyl)-1-(β-d-glucopyranosyl)-4-methylindole], and canagliflozin. These compounds are SGLT2 inhibitors with moderate SGLT1 inhibitory activity, and their IC50 values against rat SGLT1 and mouse SGLT1 were 609 and 760 nM for phloridzin, 39.4 and 41.5 nM for CGMI, and 555 and 613 nM for canagliflozin, respectively. Oral administration of these inhibitors markedly enhanced and prolonged the glucose-induced plasma active GLP-1 (aGLP-1) increase in combination treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, in normoglycemic mice and rats. CGMI, the most potent SGLT1 inhibitor among them, enhanced glucose-induced, but not fat-induced, plasma aGLP-1 increase at a lower dose compared with canagliflozin. Both CGMI and canagliflozin delayed intestinal glucose absorption after oral administration in normoglycemic rats. The combined treatment of canagliflozin and a DPP4 inhibitor increased plasma aGLP-1 levels and improved glucose tolerance compared with single treatment in both 8- and 13-week-old Zucker diabetic fatty rats. These results suggest that transient inhibition of intestinal SGLT1 promotes GLP-1 secretion by delaying glucose absorption and that concomitant inhibition of intestinal SGLT1 and DPP4 is a novel therapeutic option for glycemic control in type 2 diabetes mellitus. PMID:26105952

  12. A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.

    PubMed

    Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

    2014-10-15

    A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out

  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. Quantitation of small intestinal permeability during normal human drug absorption

    PubMed Central

    2013-01-01

    Background Understanding the quantitative relationship between a drug’s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (“Averaged Model” (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4 cm/sec) corresponding to an unstirred layer of only 45 μm. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH 7.4, suggesting

  15. Glutathione plays a role in the chick intestinal calcium absorption.

    PubMed

    Tolosa de Talamoni, N; Marchionatti, A; Baudino, V; Alisio, A

    1996-10-01

    DL-buthionine-S,R-sulfoximine (BSO) administration to vitamin D-deficient chicks treated with cholecalciferol produces a rapid decrease in the Ca2+ transfer from lumen-to-plasma and in the intestinal glutathione content. This response was reversed by addition of glutathione monoester to the intestinal sac. Variables related to the Ca2+ homeostasis such as plasma Ca and P, and intestinal calbindin D28k were not modified by BSO given to vitamin D-deficient chicks treated with cholecalciferol. Intestinal alkaline phosphatase activity, on the contrary, was highly reduced by BSO in vitamin D-deficient chicks treated with vitamin D3. This effect showed time and dose-dependency. Although the mechanism/s of action of BSO on the intestinal Ca absorption is unknown, it is quite possible that thiol groups of protein involved in the Ca2+ transport are affected by the GSH depletion and/or by block of the antioxidant ability of vitamin D3. Thus, reactive oxygen compounds would be increased and, therefore, the Ca2+ movement from lumen to plasma decreases. PMID:8916550

  16. Activation of rat intestinal mucosal mast cells by fat absorption.

    PubMed

    Ji, Yong; Sakata, Yasuhisa; Yang, Qing; Li, Xiaoming; Xu, Min; Yoder, Stephanie; Langhans, Wolfgang; Tso, Patrick

    2012-06-01

    Previous studies have linked certain types of gut mucosal immune cells with fat intake. We determined whether fat absorption activates intestinal mucosal mast cells (MMC), a key component of the gut mucosal immune system. Conscious intestinal lymph fistula rats were used. The mesenteric lymph ducts were cannulated, and the intraduodenal (i.d.) tubes were installed for the infusion of Liposyn II 20% (an intralipid emulsion). Lymphatic concentrations of histamine, rat MMC protease II (RMCPII), a specific marker of rat intestinal MMC degranulation, and prostaglandin D(2) (PGD(2)) were measured by ELISA. Intestinal MMC degranulation was visualized by immunofluorescent microscopy of jejunum sections taken at 1 h after Liposyn II gavage. Intraduodenal bolus infusion of Liposyn II 20% (4.4 kcal/3 ml) induced approximately a onefold increase in lymphatic histamine and PGD(2), ∼20-fold increase in lymphatic RMCPII, but only onefold increase in peripheral serum RMCPII concentrations. Release of RMCPII into lymph increased dose dependently with the amount of lipid fed. In addition, i.d. infusion of long-chain triacylglycerol trilinolein (C18:2 n-6, the major composite in Liposyn II) significantly increased the lymphatic RMCPII concentration, whereas medium-chain triacylglycerol tricaprylin (C8:0) did not alter lymph RMCPII secretion. Immunohistochemistry image revealed the degranulation of MMC into lamina propria after lipid feeding. These novel findings indicate that intestinal MMC are activated and degranulate to release MMC mediators to the circulation during fat absorption. This action of fatty acid is dose and chain length dependent. PMID:22461027

  17. 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

  18. 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

  19. 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 Central

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

    2014-01-01

    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

  20. Intestinal calcium absorption of women during lactation and after weaning.

    PubMed

    Kalkwarf, H J; Specker, B L; Heubi, J E; Vieira, N E; Yergey, A L

    1996-04-01

    We investigated whether intestinal calcium absorption and serum 1,25-dihydroxycholecalciferol (calcitriol) concentrations are higher in women during lactation and after weaning to compensate for calcium lost in breast milk. Measurements were obtained at 4.6 mo postpartum in 24 lactating women and 24 nonlactating women, at 9.6 mo postpartum in 24 lactating women (2.6 mo after complete weaning) and 24 nonlactating women. One-half of the women in each group were randomly assigned to receive 1 g supplemental Ca/d as calcium carbonate. Fractional calcium absorption was measured by using stable isotopic tracers 42Ca and 44Ca. Fractional absorption was 0.32+/-0.02 (+/-SEM) in both lactating and nonlactating women, but was higher in lactating women after weaning (0.37+/-0.02) compared with nonlactating postpartum control subjects (0.31+/-0.02). These effects were independent of calcium intake. Changes in serum calcitriol paralleled changes in fractional absorption. There were no differences in calcitriol concentrations between lactating and nonlactating women, but calcitriol was greater in women after weaning compared with postpartum control subjects. Lactating women who had resumed menses had higher fractional absorption and serum calcitriol than did lactating women who had not. Serum calcium and phosphorus concentrations were greater in lactating compared with nonlactating women; there were no differences between groups after weaning. We conclude that lactation stimulates increases in fractional calcium absorption and serum calcitriol, but the responses are only apparent after weaning or the resumption of menses. PMID:8599316

  1. 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

  2. Downregulation of mouse intestinal Na(+)-coupled glucose transporter SGLT1 by gum arabic (Acacia Senegal).

    PubMed

    Nasir, Omaima; Artunc, Ferruh; Wang, Kan; Rexhepaj, Rexhep; Föller, Michael; Ebrahim, Ammar; Kempe, Daniela S; Biswas, Raja; Bhandaru, Madhuri; Walter, Michael; Mohebbi, Nilufar; Wagner, Carsten A; Saeed, Amal M; Lang, Florian

    2010-01-01

    Intestinal Na(+)-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity. PMID:20110681

  3. Mechanistic and regulatory aspects of intestinal iron absorption

    PubMed Central

    Gulec, Sukru; Anderson, Gregory J.

    2014-01-01

    Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands. PMID:24994858

  4. The mechanism of intestinal absorption of phosphatidylcholine in rats

    PubMed Central

    Parthasarathy, Sampath; Subbaiah, Papasani V.; Ganguly, Jagannath

    1974-01-01

    1. The mechanism of absorption of phosphatidylcholine was studied in rats by injecting into the intestine phosphatidylcholine specifically labelled either in the fatty acid or in the glycerol moiety or with 32P, when considerable amounts of 1-acyl-lysophosphatidylcholine were found in the intestinal lumen. 2-([14C]Acyl)phosphatidylcholine gave markedly more radioactive unesterified fatty acids in the lumen, compared with the 1-([14C]acyl) derivative. Some of the radioactivity from either the fatty acid or the glycerol moiety of the injected phosphatidylcholine appeared in the mucosal triacylglycerols. 2. Injection of 32P-labelled phosphatidylcholine or 32P-labelled lysophosphatidylcholine led to the appearance of radioactive glycerylphosphorylcholine, glycerophosphate and Pi in the mucosa. 3. Rat mucosa was found to contain a highly active glycerylphosphorylcholine diesterase. 4. It was concluded that the dietary phosphatidylcholine is hydrolysed in the intestinal lumen by the pancreatic phospholipase A to 1-acylglycerylphosphorylcholine, which on entering the mucosal cell is partly reacylated to phosphatidylcholine, and the rest is further hydrolysed to glycerylphosphorylcholine, glycerophosphate, glycerol and Pi. The fatty acids and glycerophosphate are then reassembled to give triacylglycerols via the Kennedy (1961) pathway. PMID:4374941

  5. Intestinal absorption of chromium as affected by wheat bran

    SciTech Connect

    Keim, K.S.; Holloway, C.L.; Hegsted, M.

    1986-03-01

    This study was designed to investigate the influence of dietary fiber, as found in wheat bran, on the absorption of chromium. Twenty male Sprague-Dawley rats were divided into two groups of 10. The control was fed a semi-purified diet containing casein, methionine, cornstarch, sucrose, corn oil, mineral and vitamin mix, and choline bitartrate. The experimental group was fed the same diet but with soft red winter wheat bran added to a level of 35% of the diet at the expense of sucrose. To determine chromium absorption and uptake by selected tissues, rats were fasted for 24 hr, fed 5 g of the respective diet, 2 hr later intubated with 100..mu..Ci of Cr-51of sacrificed 24 hr later. The rats wee housed in metabolic cages after the Cr-51 intubation. The addition of wheat brand to the diet did not significantly affect chromium absorption as measured by percent dose of Cr-51 in the 24 hr urine. The percent dose in the control group was 0.68 +/- 0.20% (mean +/- SEM) and in the experimental group 0.63 +/- 0.24% (mean +/-SEM) (N.S.). The cr-51 uptake of liver, spleen, jejunum, and blood was not statistically different between groups. These results indicate that dietary fiber as found in wheat bran does not impair intestinal absorption of chromium.

  6. 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.

  7. [The current concepts on the absorption of monosaccharides, amino acids and peptides in the mammalian small intestine].

    PubMed

    Timofeeva, N M; Iezuitova, N N; Gromova, L V

    2000-01-01

    The review is mainly devoted to the development of ideas about absorption, or transport, of basic nutrients in the small intestine in humans and higher animal. The absorption processes have been characterized on the example of such substances, vital for organism, as carbohydrates and proteins. The review considers a molecular structure of transporters--protein molecules, which take part in a transfer of the products of lumenal and membrane digestion of carbohydrates (glucose, galactose, fructose) and proteins (amino acids, oligopeptides) across the enterocyte membranes. An information is presented about genetic disturbances of transport of certain amino acids during such diseases as Hartnup disease, cystinuria, and iminoglycineuria. PMID:11094795

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

    PubMed Central

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

    2012-01-01

    SUMMARY 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 extra-intestinal 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. PMID:22980325

  9. [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. PMID:27071269

  10. 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

  11. Dietary Fructose Inhibits Intestinal Calcium Absorption and Induces Vitamin D Insufficiency in CKD

    PubMed Central

    Douard, Veronique; Asgerally, Abbas; Sabbagh, Yves; Sugiura, Shozo; Shapses, Sue A.; Casirola, Donatella

    2010-01-01

    Renal disease leads to perturbations in calcium and phosphate homeostasis and vitamin D metabolism. Dietary fructose aggravates chronic kidney disease (CKD), but whether it also worsens CKD-induced derangements in calcium and phosphate homeostasis is unknown. Here, we fed rats diets containing 60% glucose or fructose for 1 mo beginning 6 wk after 5/6 nephrectomy or sham operation. Nephrectomized rats had markedly greater kidney weight, blood urea nitrogen, and serum levels of creatinine, phosphate, and calcium-phosphate product; dietary fructose significantly exacerbated all of these outcomes. Expression and activity of intestinal phosphate transporter, which did not change after nephrectomy or dietary fructose, did not correlate with hyperphosphatemia in 5/6-nephrectomized rats. Intestinal transport of calcium, however, decreased with dietary fructose, probably because of fructose-mediated downregulation of calbindin 9k. Serum calcium levels, however, were unaffected by nephrectomy and diet. Finally, only 5/6-nephrectomized rats that received dietary fructose demonstrated marked reductions in 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 levels, despite upregulation of 1α-hydroxylase. In summary, excess dietary fructose inhibits intestinal calcium absorption, induces marked vitamin D insufficiency in CKD, and exacerbates other classical symptoms of the disease. Future studies should evaluate the relevance of monitoring fructose consumption in patients with CKD. PMID:19959720

  12. Effects of luminal glucose versus nonnutritive infusates on jejunal mass and absorption in the rat.

    PubMed

    Richter, G C; Levine, G M; Shiau, Y F

    1983-11-01

    These studies were designed to better understand the effects of luminal nutrition on intestinal mass and function. Parenterally nourished rats received a midjejunal infusion of either 0.9% saline, 10% glucose, 10% 3-O-methyl glucose, or 30% glucose. A fifth group underwent sham operation. After 7 days, intestinal mass and in vitro glucose and leucine uptake were measured in the intestine just distal to the infusion site. Luminal infusion led to greater intestinal mass in all groups compared to controls, but only the 10% and 30% glucose groups had significantly greater overall glucose uptake. Kinetic analysis revealed a greater apparent maximal transport rate in both glucose groups. The 30% glucose group had a greater apparent maximal transport rate for leucine and permeability for glucose and leucine. These data confirmed that "work load," in addition to luminal nutrition, maintains intestinal mass. However, adaptation of intestinal transport is more specific and appears to be regulated both by substrate metabolism and caloric density. PMID:6413290

  13. 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

  14. 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

  15. Vascular perfused segments of human intestine as a tool for drug absorption.

    PubMed

    Wei, Yansheng; Neves, Liomar A A; Franklin, Tammy; Klyuchnikova, Nadya; Placzek, Benjamin; Hughes, Helen M; Curtis, C Gerald

    2009-04-01

    Blood-based vascular perfusion of isolated segments of human jejunum was developed as a tool for drug absorption studies before clinical trials. Acceptance criteria for viable human gut preparations included stable blood flow, arterial pressure, glucose utilization, active peristalsis, oxygen uptake, less than 3% absorption of a 70,000 mol. wt. dextran, and a ratio of first-order absorption rate constants (k(a)) of antipyrine to terbutaline of > or =1.4. Mannitol absorption was less than that of antipyrine but larger than that of terbutaline and could not be used as a negative control in absorption studies with human intestine. In separate perfusions (n = 3) a cassette of nine drugs was administered into the gut lumen, and the net absorption of each drug into the circulation was measured over 75 min. Using the mean values of k(a), the test compounds could be ranked into four groups: group 1: sulfasalazine and furosemide, k(a) = 3.9 to 4.0 x 10(-3) min(-1); group 2: cimetidine, timolol, nadolol, and ranitidine, k(a) = 6.4 to 8.3 x 10(-3) min(-1); group 3: atenolol and metoprolol, k(a) = 9.6 x 10(-3) min(-1); and group 4: theophylline, k(a) = 17.5 x 10(-3) min(-1). The rationale for evaluating yet another oral absorption system was as follows: first, a human gut segment with an intact vascular system is the closest system available to a clinical trial without performing one; and second, the data generated would be a direct measure of net drug transport from the gut lumen into the vascular circulation under near physiological conditions, which is not possible in models lacking a blood supply. PMID:19118133

  16. Enhancement of intestinal water absorption and sodium transport by glycerol in rats.

    PubMed

    Wapnir, R A; Sia, M C; Fisher, S E

    1996-12-01

    Glycerol (Gly) is a hydrophilic, absorbable, and energy-rich solute that could make water absorption more efficient. We investigated the use of Gly in a high-energy beverage containing corn syrup (CS) by using a small intestine perfusion procedure in the rat, an approach shown earlier to provide good preclinical information. The effectiveness of several formulations with Gly and CS was compared with commercial products and to experimental formulas where Gly substituted for glucose (Glc). The CS-Gly combination was more effective than preparations on the market containing sucrose and Glc-fructose syrups (G-P and G-L, respectively) in maintaining a net water absorption balance in the test jejunal segment [CS-Gly = 0.21 +/- 0.226, G-L = -1.516 +/- 0.467, and G-P = -0.299 +/- 0.106 (SE) microliter.min-1.cm-1 (P = 0.0113)] and in reducing sodium release into the lumen [CS-Gly = -133.2 +/- 16.2, G-L = -226.7 +/- 25.2, and G-P = -245.6 +/- 23.4 nmol.min-1.cm-1 (P = 0.0022)]. In other preparations, at equal CS concentrations (60 and 80 g/l, respectively), Gly clearly improved net water absorption over a comparable Glc-containing product [CS60-Gly = 0.422 +/- 0.136 and CS80-Gly = 0.666 +/- 0.378 vs. CS60-Glc = -0.282 +/- 0.200 and CS80-Glc = -1.046 +/- 0.480 microliters.min-1.cm-1 (P = 0.0019)]. On the basis of the data of this rat intestine perfusion model, Gly could be a useful ingredient in energy-rich beverages and might enhance fluid absorption in humans. PMID:9018501

  17. 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. PMID:22980325

  18. 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

  19. [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. PMID:25993803

  20. [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

  1. 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.

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

    PubMed

    Ferrebee, Courtney B; Dawson, Paul A

    2015-03-01

    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

  3. 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

  4. Effect of intestinal fluid flux on ibuprofen absorption in the rat intestine.

    PubMed

    Lane, Majella E; Levis, Karl A; Corrigan, Owen I

    2006-02-17

    Previously the apparent permeability coefficient (P(app)) of ibuprofen was observed to vary depending on the perfusion medium employed. The present work explores the possible contributions to these differences. Studies were undertaken using an in situ single pass rat gut technique. Lumenal drug concentrations and plasma drug levels were assayed by HPLC. Absorption rate constants (k(0)) were determined from fractions of drug unabsorbed from the intestineat steady state. Plasma data were fitted to a two compartment open model with zero-order input. Significant differences in net fluid flux were observed between the various buffered perfusion media, with fluxes varying from -0.044+/-0.006 ml min(-1) to +0.057+/-0.013 ml min(-1), the lower and negative values occurring for lower pH media and the larger positive values tending to occur with media of higher pH. A linear relationship was found between the P(app) of ibuprofen and net water flux (y=1.13+11.3x; r(2)=0.80). Apparent zero-order rate constants for ibuprofen appearance in plasma correlated well with absorption rate constants estimated from steady state lumenal drug concentration [k(0(gut))]. From the linear relationship between P(app) and fluid flux a normalized P(app) for ibuprofen (i.e. the P(app) in the absence of net fluid flux) of 1.1 x 10(-4)cms(-1) was determined Net lumenal fluid flux is dependent on perfusion medium composition and significantly alters ibuprofen absorption. The differences observed for P(app) were reflected in systemic drug absorption concentrations. The findings of these studies underline the importance of standardizing the osmolarity of experimental media used for the determination of intestinal permeability data. PMID:16376032

  5. 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. PMID:27041321

  6. 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)

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

    PubMed

    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

  8. 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

  9. Effects of Onion (Allium cepa L.) Extract Administration on Intestinal α-Glucosidases Activities and Spikes in Postprandial Blood Glucose Levels in SD Rats Model

    PubMed Central

    Kim, Sun-Ho; Jo, Sung-Hoon; Kwon, Young-In; Hwang, Jae-Kwan

    2011-01-01

    Diets high in calories and sweetened foods with disaccharides frequently lead to exaggerated postprandial spikes in blood glucose. This state induces immediate oxidant stress and free radicals which trigger oxidative stress-linked diabetic complications. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase and α-glucosidases, in the digestive organs. Therefore, the inhibitory activity of Korean onion (Allium cepa L.) extract against rat intestinal α-glucosidases, such as sucrase, maltase, and porcine pancreatic α-amylase were investigated in vitro and in vivo. The content of quercetin in ethyl alcohol extract of onion skin (EOS) was 6.04 g/100 g dried weight of onion skin. The in vitro half-maximal inhibitory concentrations (IC50) of EOS and quercetin, a major phenolic in onion, on rat intestinal sucrase were 0.40 and 0.11 mg/mL, respectively. The postprandial blood glucose lowering effects of EOS and quercetin were compared to a known type 2 diabetes drug (Acarbose), a strong α-glucosidase inhibitor in the Sprague-Dawley (SD) rat model. In rats fed on sucrose, EOS significantly reduced the blood glucose spike after sucrose loading. The area under the blood glucose-time curve (AUClast) in EOS-treated SD rats (0.5 g-EOS/kg) was significantly lower than in untreated SD rats (259.6 ± 5.1 vs. 283.1 ± 19.2 h·mg/dL). The AUClast in quercetin-treated SD rats (0.5 g-quercetin/kg) was similar to in EOS-treated group (256.1 ± 3.2 vs. 259.6 ± 5.1 h·mg/dL). Results from this study indicates that although quercetin does have blood glucose lowering potential via α-glucosidase inhibition, there are other bioactive compounds present in onion skin. Furthermore, the effects of two weeks administration of EOS in a high carbohydrate-dietary mixture (Pico 5053) on sucrase and maltase activities in intestine were evaluated in SD rat model. Compared to

  10. Effect of ethanolic extract of Cryptolepis sanguinolenta stem on in vivo and in vitro glucose absorption and transport: Mechanism of its antidiabetic activity

    PubMed Central

    Ajayi, A. F.; Akhigbe, R. E.; Adewumi, O. M.; Okeleji, L. O.; Mujaidu, K. B.; Olaleye, S. B.

    2012-01-01

    Objective: Extracts from various morphological parts of Cryptolepis sanguinolenta are widely used traditionally in folklore medicine in many parts of the world for the management, control, and/or treatment of a plethora of human ailments, including diabetes mellitus. In order to scientifically appraise some of the ethnomedical uses of Cryptolepis sanguinolenta, the present study was undertaken to investigate its influence at varying doses on intestinal glucose absorption and transport in relation to its hypoglycemic and hypolipidemic effects in rat experimental paradigms. Materials and Methods: The animals used were divided into four groups. Control animals received 2 ml of distilled water, while treated groups received 50, 150, and 250 mg/kg bw of Cryptolepis sanguinolenta extract per oral respectively daily for 21 days. Results: Cryptolepis sanguinolenta led to a significant decrease in glucose transport and absorption. It also caused significant reductions in plasma glucose, total cholesterol, triglyceride, and LDL cholesterol. Biochemical changes observed were suggestive of dose dependence. Histopathological studies also showed increased sizes of β cells of the pancreas. Conclusion: The findings in these normoglycemic laboratory animals suggest that Cryptolepis sanguinolenta has hypoglycemic and hypolipidemic activities, possibly by reducing glucose absorption and transport, and enhancing the structural and functional abilities of the β cells. This is the first study to report the effect of Cryptolepis sanguinolenta on intestinal glucose absorption. This effect could be attributed to its major bioactive principle, cryptolepine, an indoloquinoline alkaloid. This study thus lends credence to the use of Cryptolepis sanguinolenta in the management of diabetes mellitus. PMID:22701855

  11. 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

  12. Characterization of intestinal absorption of mizoribine mediated by concentrative nucleoside transporters in rats.

    PubMed

    Mori, Nobuhiro; Yokooji, Tomoharu; Kamio, Yoshihiro; Murakami, Teruo

    2008-05-31

    Mizoribine, an imidazole nucleoside, is an inhibitor of purine synthesis and has been used as an orally available immunosuppressive agent in human renal transplantation. In the present study, the intestinal absorption of mizoribine was characterized by examining the contribution of concentrative nucleoside transporters (CNT1, CNT2) in rats. When mizoribine was administered orally in conscious rats, the bioavailability of mizoribine estimated by urinary excretion percentage of unchanged mizoribine was a dose dependent: 53.1+/-6.0% at 5 mg/kg and 24.0+/-5.1% at 20 mg/kg. In in-situ loop studies, the disappearance rate, or absorption rate, of mizoribine from the intestinal lumen was comparable between 1 and 5 mg/kg, but significantly lower at 25 mg/kg. Coadministration of adenosine (a substrate of both CNT1 and CNT2), thymidine (a CNT1 substrate) and inosine (a CNT2 substrate) significantly suppressed the intestinal mizoribine absorption, depending on the nucleoside concentrations coadministered. Gemcitabine (a pyrimidine nucleoside analogue, a CNT1 substrate) and ribavirin (a purine nucleoside analog, a CNT2 substrate) also significantly suppressed the mizoribine intestinal absorption. Bile salts such as sodium cholate and sodium glycocholate (10 mM) also significantly suppressed the intestinal mizoribine absorption, but not ribavirin absorption. Mizoribine is an amphoteric compound, however, the suppression of intestinal absorption by bile salts was not ascribed to the electrostatic interaction or micellar formation between mizoribine and bile salts. In conclusion, the intestinal absorption of mizoribine is mediated by CNT1 and CNT2, and nucleoside-derived drugs such as gemcitabine and ribavirin can suppress the intestinal absorption of mizoribine. Bile salts such as sodium glycocholate were also found to cause interaction with mizoribine. PMID:18371949

  13. Lack of relationship between activity of intestinal alkaline phosphatase and calcium or phosphate absorption.

    PubMed

    Asteggiano, C; Tolosa, N; Pereira, R; Moreno, J; Cañas, F

    1981-01-01

    The effects of vitamin D3 and the aqueous extract of Solanum malacoxylon on intestinal alkaline phosphatase and tissue phosphate content were studied on rachitic chicks treated with large doses of ethane-1-hydroxy-1,1 diphosphonate (EHDP). The EHDP treatment blocks the increase of intestinal calcium or phosphate absorption induced by the vitamin D3, while it has no effects on the rise of intestinal alkaline phosphatase activity or the increment in tissue phosphate content. The lack of correlation between the increment of alkaline phosphatase and that of Ca or phosphate absorption in vitamin D3 plus EHDP treated chicks excludes a participation of the alkaline phosphatase in the mechanism of Ca or P intestinal absorption. The Ca or phosphorus absorption are elicited specifically by 1,25-(OH)2-D3, while alkaline phosphatase activity and phosphate tissue concentration respond to a broader spectrum of stimuli. PMID:6316731

  14. Disruption of retinoblastoma protein expression in the intestinal epithelium impairs lipid absorption.

    PubMed

    Choi, Pamela M; Guo, Jun; Erwin, Christopher R; Wandu, Wambui S; Leinicke, Jennifer A; Xie, Yan; Davidson, Nicholas O; Warner, Brad W

    2014-05-15

    We previously demonstrated increased villus height following genetic deletion, or knockout, of retinoblastoma protein (Rb) in the intestinal epithelium (Rb-IKO). Here we determined the functional consequences of augmented mucosal growth on intestinal fat absorption and following a 50% small bowel resection (SBR). Mice with constitutively disrupted Rb expression in the intestinal epithelium (Rb-IKO) along with their floxed (wild-type, WT) littermates were placed on a high-fat diet (HFD, 42% kcal fat) for 54 wk. Mice were weighed weekly, and fat absorption, indirect calorimetry, and MRI body composition were measured. Rb-IKO mice were also subjected to a 50% SBR, followed by HFD feeding for 33 wk. In separate experiments, we examined intestinal fat absorption in mice with conditional (tamoxifen-inducible) intestinal Rb (inducible Rb-IKO) deletion. Microarray revealed that the transcriptional expression of lipid absorption/transport genes was significantly reduced in constitutive Rb-IKO mice. These mice demonstrated greater mucosal surface area yet manifested paradoxically impaired intestinal long-chain triglyceride absorption and decreased cholesterol absorption. Despite attenuated lipid absorption, there were no differences in metabolic rate, body composition, and weight gain in Rb-IKO and WT mice at baseline and following SBR. We also confirmed fat malabsorption in inducible Rb-IKO mice. We concluded that, despite an expanded mucosal surface area, Rb-IKO mice demonstrate impaired lipid absorption without compensatory alterations in energy homeostasis or body composition. These findings underscore the importance of delineating structural/functional relationships in the gut and suggest a previously unknown role for Rb in the regulation of intestinal lipid absorption. PMID:24742992

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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. PMID:25919764

  20. 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.

  1. New insights into the molecular mechanism of intestinal fatty acid absorption

    PubMed Central

    Wang, Tony Y.; Liu, Min; Portincasa, Piero; Wang, David Q.-H.

    2013-01-01

    Background Dietary fat is the most important energy source of all the nutrients. Fatty acids, stored as triacylglycerols in the body, are an important reservoir of stored energy and derive primarily from animal fats and vegetable oils. Design Although the molecular mechanisms for the transport of water-insoluble amphipathic fatty acids across cell membranes have been debated for many years, it is now believed that the dominant means for intestinal fatty acid uptake is via membrane-associated fatty acid-binding proteins, i.e., fatty acid transporters on the apical membrane of enterocytes. Results These findings indicate that intestinal fatty acid absorption is a multistep process that is regulated by multiple genes at the enterocyte level, and intestinal fatty acid absorption efficiency could be determined by factors influencing intraluminal fatty acid molecules across the brush border membrane of enterocytes. To facilitate research on intestinal, hepatic and plasma triacylglycerol metabolism, it is imperative to establish standard protocols for precisely and accurately measuring the efficiency of intestinal fatty acid absorption in humans and animal models. In this review, we will discuss the chemical structure and nomenclature of fatty acids and summarize recent progress in investigating the molecular mechanisms underlying the intestinal absorption of fatty acids, with a particular emphasis on the physical-chemistry of intestinal lipids and the molecular physiology of intestinal fatty acid transporters. Conclusions A better understanding of the molecular mechanism of intestinal fatty acid absorption should lead to novel approaches to the treatment and the prevention of fatty acid-related metabolic diseases that are prevalent worldwide. PMID:24102389

  2. 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.

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

    PubMed

    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

  4. 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

  5. Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters.

    PubMed

    Werdenberg, D; Joshi, R; Wolffram, S; Merkle, H P; Langguth, P

    2003-09-01

    Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono- and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined using isolated intestinal mucosa as well as Caco-2 cell monolayers, in order to obtain estimates of the fraction of the dose absorbed for these compounds. Relationships between the physicochemical properties of the fumaric acid esters and their biological responses were investigated. The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models. It also showed the highest permeability in the Caco-2 cell model. However, in permeation experiments with intestinal mucosa in Ussing-type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue. The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n-propylhydrogen fumarate and n-pentyl hydrogen fumarate increased with an increase in their lipophilicity, however, their presystemic metabolism rates likewise increased with increasing ester chain length. It is concluded that for fumarates, an increase in intestinal permeability of the more lipophilic derivatives is counterbalanced by an increase in first-pass extraction. PMID:12973823

  6. [Intestinal absorption of different combinations of active compounds from Gegenqinlian decoction by rat single pass intestinal perfusion in situ].

    PubMed

    An, Rui; Zhang, Hua; Zhang, Yi-Zhu; Xu, Ran-Chi; Wang, Xin-Hong

    2012-12-01

    The aim is to study the intestinal absorption of different combinations of active compounds out of Gegenqinlian decoction. Rat single pass intestinal perfusion model with jugular vein cannulated was used. Samples were obtained continuously from the outlet perfusate and the mesenteric vein. The levels of puerarin, daidzin, liquilitin, baicalin, wogonoside, jatrorrhizine, berberine and palmatine were determined by LC-MS/MS and their permeability coefficients were calculated. The results showed that Glycyrrhiza could promote the absorption of the active ingredients in Pueraria which is the monarch herb; meanwhile, Pueraria also played a role in promoting the absorption of liquilitin. Based on the Gegenqinlian decoction and the different combinations experiments, the results concerning the absorption of baicalin and wogonoside were as follows. For baicalin, Pueraria and Glycyrrhiza could promote its absorption and the effect of Pueraria was more obvious. For wogonoside, Pueraria could also promote its absorption, while Glycyrrhiza played a opposite role. Pueraria and Glycyrrhiza both played a part in promoting the absorption of jateorhizine, berberine and palmatine, the effective compounds in Coptis. PMID:23460978

  7. Intestinal Fluid and Glucose Transport in Wistar Rats following Chronic Consumption of Fresh or Oxidised Palm Oil Diet

    PubMed Central

    Obembe, Agona O.; Owu, Daniel U.; Okwari, Obem O.; Antai, Atim B.; Osim, Eme E.

    2011-01-01

    Chronic ingestion of thermoxidized palm oil causes functional derangement of various tissues. This study was therefore carried out to determine the effect of chronic ingestion of thermoxidized and fresh palm oil diets on intestinal fluid and glucose absorption in rats using the everted sac technique. Thirty Wistar rats were divided into three groups of 10 rats per group. The first group was the control and was fed on normal rat chow while the second (FPO) and third groups (TPO) were fed diet containing either fresh or thermoxidized palm oil (15% wt/wt) for 14 weeks. Villus height and crypt depth were measured. The gut fluid uptake and gut glucose uptake were significantly (P < .001) lower in the TPO group than those in the FPO and control groups, respectively. The villus height in the TPO was significantly (P < .01) lower than that in FPO and control. The villus depth in TPO was significantly (P < .05) higher than that in FPO and control groups, respectively. These results suggest that ingestion of thermoxidized palm oil and not fresh palm oil may lead to distortion in villus morphology with a concomitant malabsorption of fluid and glucose in rats due to its harmful free radicals. PMID:21991537

  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. 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

  10. 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.

  11. 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)

  12. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    PubMed

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

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. PMID:26707414

  13. Intestinal absorption of water-soluble vitamins in health and disease

    PubMed Central

    Said, Hamid M.

    2014-01-01

    Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current

  14. Intestinal absorption characteristics of imperialine: in vitro and in situ assessments

    PubMed Central

    Lin, Qing; Ling, Li-qin; Guo, Ling; Gong, Tao; Sun, Xun; Zhang, Zhi-rong

    2015-01-01

    Aim: Imperialine is an effective compound in the traditional Chinese medicine chuanbeimu (Bulbus Fritillariae Cirrhosae) that has been used as antitussive/expectorant in a clinical setting. In this study we investigated the absorption characteristics of imperialine in intestinal segments based on an evaluation of its physicochemical properties. Methods: Caco-2 cells were used to examine uptake and transport of imperialine in vitro, and a rat in situ intestinal perfusion model was used to characterize the absorption of imperialine. The amount of imperialine in the samples was quantified using LC-MS/MS. Results: The aqueous solubility and oil/water partition coefficient of imperialine were determined. This compound demonstrated a relatively weak alkalinity with a pKa of 8.467±0.028. In Caco-2 cells, the uptake of imperialine was increased with increasing pH in medium, but not affected by temperature. The apparent absorptive and secretive coefficient was (8.39±0.12)×10−6 cm/s and (7.78±0.09)×10−6 cm/s, respectively. Furthermore, neither the P-glycoprotein inhibitor verapamil nor Niemann-Pick C1-Like 1 transporter inhibitor ezetimibe affected the absorption and secretion of imperialine in vitro. The in situ intestinal perfusion study showed that the absorption parameters of imperialine varied in 4 intestinal segments (duodenum, jejunum, ileum and colon) with the highest ones in the colon, where a greater number of non-ionized form of imperialine was present. Conclusion: The intestinal absorptive characteristics of imperialine are closely related to its physicochemical properties. The passive membrane diffusion dominates the intestinal absorption of imperialine. PMID:26051111

  15. Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

    PubMed Central

    Zhou, Wei; Di, Liu-qing; Wang, Juan; Shan, Jin-jun; Liu, Shi-jia; Ju, Wen-zheng; Cai, Bao-chang

    2012-01-01

    Aim: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. Methods: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. Results: In the in vitro Caco-2 cell model, the mean apparent permeability value (Papp-value) was 4.15×10-7 cm/s in the apical-to-basolateral (AP-BL) direction. At the concentrations of 2.6–10.4 μg/mL, the efflux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The Papp-values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the Papp-values. The intake transporter SGLT1 inhibitor mannitol did not cause significant change in the Papp-values. In the in situ intestinal perfusion model, both the absorption rate constant (Ka) and the effective permeability (Peff-values) following perfusion of FTA 2.6, 5.2 and 10.4 μg/mL via the duodenum, jejunum and ileum had no significant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the Peff-values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the Peff-values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the

  16. 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.

  17. 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. PMID:27084488

  18. 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

  19. In vitro absorption of γ-globulin by neonatal intestinal epithelium of the pig

    PubMed Central

    Lecce, James G.

    1966-01-01

    1. An in vitro method, using fluorescent γ-globulin and everted neonatal pig's intestinal slices, for the study of the active transport of large molecules is described. 2. Uptake of γ-globulin occurred within 15 min and required no exogenous substrates. 3. In vitro absorption of γ-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 γ-globulin. 4. Rings of everted intestinal epithelium remained active (still absorbed γ-globulin) after incubating for 4-6 hr in balanced salt solution (BSS). 5. Uptake of γ-globulin required oxygen and sodium and was reversibly inhibited by metabolic antagonists such as iodoacetate, arsenate, fluoride, 4,6-dinitro-ϕ-cresol, phlorrhizin, anaerobiosis and cold. Under the conditions of the test, large colloidal molecules did not inhibit uptake of γ-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. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:4164327

  20. Effect of glucose on jejunal water and solute absorption in the presence of glycodeoxycholate and oleate in man.

    PubMed

    Brown, B D; Ammon, H V

    1981-08-01

    Jejunal perfusion studies were performed in 12 healthy volunteers to study the effects of 14 and 56 mM glucose on fluid secretion induced by 5 mM glycodeoxycholate on 7 mM oleate. Glucose enhanced water absorption under control conditions and reduced water secretion induced by glycodeoxycholate or oleate (P less than 0.01). As has been observed previously, glycodeoxycholate and oleate inhibited glucose absorption (P less than 0.001) and significant linear relationships existed between net water movement and glucose absorption. Glycodeoxycholate also reduced the absorption of 14 mM arabinose (P less than 0.05) and oleate reduced the absorption of 56 mM mannitol (P less than 0.05). Reduced solute absorption in the presence of glycodeoxycholate and oleate, therefore, cannot be attributed to an effect on active transport alone. The relationships between sodium transport and water absorption varied with the glucose concentration in the perfusion solutions. Similarly, the relationships between glucose absorption and sodium absorption varied with glucose concentration. The data suggest that a significant amount of glucose can be absorbed without concomitant absorption of sodium. The data indicate that glucose absorption can stimulate water absorption directly without the mediation of sodium and that water movement follows glucose at a rate which maintains isotonicity. PMID:7261835

  1. Increased intestinal absorption in the era of teduglutide and its impact on management strategies in patients with short bowel syndrome-associated intestinal failure.

    PubMed

    Seidner, Douglas L; Schwartz, Lauren K; Winkler, Marion F; Jeejeebhoy, Khursheed; Boullata, Joseph I; Tappenden, Kelly A

    2013-03-01

    Short bowel syndrome-associated intestinal failure (SBS-IF) as a consequence of extensive surgical resection of the gastrointestinal (GI) tract results in a chronic reduction in intestinal absorption. The ensuing malabsorption of a conventional diet with associated diarrhea and weight loss results in a dependency on parenteral nutrition and/or intravenous fluids (PN/IV). A natural compensatory process of intestinal adaptation occurs in the years after bowel resection as the body responds to a lack of sufficient functional nutrient-processing intestinal surface area. The adaptive process improves bowel function but is a highly variable process, yielding different levels of symptom control and PN/IV independence among patients. Intestinal rehabilitation is the strategy of maximizing the absorptive capacity of the remnant GI tract. The approaches for achieving this goal have been limited to dietary intervention, antidiarrheal and antisecretory medications, and surgical bowel reconstruction. A targeted pharmacotherapy has now been developed that improves intestinal absorption. Teduglutide is a human recombinant analogue of glucagon-like peptide 2 that promotes the expansion of the intestinal surface area and increases the intestinal absorptive capacity. Enhanced absorption has been shown in clinical trials by a reduction in PN/IV requirements in patients with SBS-IF. This article details the clinical considerations and best-practice recommendations for intestinal rehabilitation, including optimization of fluids, electrolytes, and nutrients; the integration of teduglutide therapy; and approaches to PN/IV weaning. PMID:23343999

  2. Chronic nifedipine dosing enhances cephalexin bioavailability and intestinal absorption in conscious rats.

    PubMed

    Berlioz, F; Lepére-Prevot, B; Julien, S; Tsocas, A; Carbon, C; Rozé, C; Farinotti, R

    2000-11-01

    Cephalexin, a beta-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several beta-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats. The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration. Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration. In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats. Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man. PMID:11038150

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

    USGS Publications Warehouse

    Eastin, W.C., Jr.; 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.

  4. Regulation of Electroneutral NaCl Absorption by the Small Intestine

    PubMed Central

    Kato, Akira; Romero, Michael F.

    2014-01-01

    Na+ and Cl− movement across the intestinal epithelium occurs by several interconnected mechanisms: (1) nutrient coupled Na+ absorption; (2) electroneutral NaCl absorption; (3) electrogenic Cl− secretion by CFTR; and (4) electrogenic Na+ absorption by ENaC. All of these transport modes require a favorable electrochemical gradient maintained by the basolateral Na+-K+-ATPase, a Cl− channel and K+ channels. Electroneutral NaCl absorption is observed from the small intestine to distal colon. This transport is mediated by apical Na+/H+ (NHE2/3) and Cl−/HCO3 − (Slc26a3/a6, others) exchangers that provide the major route of NaCl absorption. Electroneutral NaCl absorption and Cl− secretion by CFTR are oppositely regulated by the autonomic nerve system, immune system, and endocrine system via PKAα, PKCα, cGKII, and/or SGK1. This integrated regulation requires the formation of macromolecular complexes, which mediated by NHERF family of scaffold proteins, and involve internalization of NHE3. Using knockout mice and human mutations, a more detailed understanding of the integrated as well as subtle regulation of electroneutral NaCl absorption by the mammalian intestine has emerged. PMID:21054167

  5. In vitro characterization of the intestinal absorption of methylmercury using a Caco-2 cell model.

    PubMed

    Vázquez, Marta; Vélez, Dinoraz; Devesa, Vicenta

    2014-02-17

    Methylmercury (CH3Hg) is one of the forms of mercury found in food, particularly in seafood. Exposure to CH3Hg is associated with neurotoxic effects during development. In addition, methylmercury has been classified by the International Agency for Research on Cancer as a possible human carcinogen. Although the diet is known to be the main source of exposure, few studies have characterized the mechanisms involved in the absorption of this contaminant. The present study examines the absorption process using the Caco-2 cell line as a model of the intestinal epithelium. The results indicate that transport across the intestinal cell monolayer in an absorptive direction occurs mainly through passive transcellular diffusion. This mechanism coexists with carrier-mediated transcellular transport, which has an active component. The participation of H(+)- and Na(+)-dependent transport was observed. Inhibition tests point to the possible participation of amino acid transporters (B(0,+) system, L system, and/or y(+)L system) and organic anion transporters (OATs). Our study suggests the participation in CH3Hg absorption of transporters that have already been identified as being responsible for the transport of this species in other systems, although further studies are needed to confirm their participation in intestinal absorption. It should be noted that CH3Hg experiences important cellular acumulation (48-78%). Considering the toxic nature of this contaminant, this fact could affect intestinal epithelium function. PMID:24397474

  6. 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

  7. SGLT-1 Transport and Deglycosylation inside Intestinal Cells Are Key Steps in the Absorption and Disposition of Calycosin-7-O-β-d-Glucoside in Rats.

    PubMed

    Shi, Jian; Zheng, Haihui; Yu, Jia; Zhu, Lijun; Yan, Tongmeng; Wu, Peng; Lu, Linlin; Wang, Ying; Hu, Ming; Liu, Zhongqiu

    2016-03-01

    Hydrolysis by lactase-phloridzin hydrolase (LPH) is the first and critical step in the absorption of isoflavonoid glucosides. However, the absorption characteristics of calycosin-7-O-β-d-glucoside (CG) slightly differ from other isoflavonoid glucosides. In this study, we used the rat intestinal perfusion model and performed pharmacokinetic studies and in vitro experiments to determine the factors influencing CG absorption and disposition. After oral administration of isoflavonoid glucosides, LPH was found to play minimal or no role on the hydrolysis of CG, in contrast to that of daidzin. CG was mainly transported into the small intestinal cells by sodium-dependent glucose transporter 1 (SGLT-1) as intact. This pathway could be the main mechanism underlying the high permeability of CG in the small intestine. CG was likely to be hydrolyzed in enterocytes to its aglycone calycosin by broad-specific β-glucuronides (BSβG) and glucocerebrosidase or rapidly metabolized. Calycosin was also rapidly and extensively metabolized to 3'-glucuronide in the enterocytes and liver, and the glucuronidation rates of calycosin and CG were much higher in the former. The metabolites were also transported into lumen by breast cancer resistance protein and multidrug resistance-associated protein 2. In conclusion, the enterocytes could be an important site for CG absorption, deglycosylation, and metabolism in rats. This study could contribute to the theoretical foundation and mechanism of absorption and disposition of flavonoid compounds. PMID:26658676

  8. In Situ Absorption in Rat Intestinal Tract of Solid Dispersion of Annonaceous Acetogenins

    PubMed Central

    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

  9. 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.

  10. 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. PMID:25900515

  11. Absorption and elimination of imatinib through the rat intestine in vitro.

    PubMed

    Kralj, Eva; Zakelj, Simon; Trontelj, Jurij; Roškar, Robert; Cernelč, Peter; Kristl, Albin

    2014-01-01

    Imatinib is a potent selective inhibitor of tyrosine kinases and is used primarily in the treatment of chronic myeloid leukemia and the gastrointestinal stromal tumour. Although, it is well established that imatinib is a substrate of several transport proteins which are also active in the intestinal mucosa, the mechanisms of imatinib intestinal absorption and elimination were not systematically investigated yet. To do that, we used a Sweetana-Grass type of diffusion chambers with segments of rat intestine as a model of the intestinal mucosa, measured the permeability coefficients of imatinib and its major metabolite (N-desmethyl imatinib) in both directions with and without specific and general inhibition of active transport, and calculated the efflux ratios. The results show that the good bioavailability of imatinib is highly likely achieved by its active absorption from the intestine and that its active elimination through the intestinal mucosa is mediated by a synergistic activity of organic cation transporter 1 in the basolateral membrane and the added activity of two efflux proteins (P-glycoprotein and breast cancer resistant protein) in the apical membrane of enterocytes of the rat ileum. Interestingly, it was found that N-desmethyl imatinib is only transported by P-glycoprotein. PMID:24219857

  12. Inhibition of intestinal absorption of cholesterol by surface-modified nanostructured aluminosilicate compounds.

    PubMed

    Gershkovich, Pavel; Darlington, Jerry; Sivak, Olena; Constantinides, Panayiotis P; Wasan, Kishor M

    2009-07-01

    The aim of this work was to assess the ability of aqueous suspensions of surface-modified nanostructured aluminosilicate (NSAS) compounds to reduce the intestinal absorption of cholesterol in a rat model. The rats were divided into 10 treatment groups which included several NSAS compounds at various doses, ezetimibe at 10 mg/kg, stigmastanol at 50 mg/kg, and normal saline. All compounds and controls were independently administered by oral gavage and then a mixture of [(3)H]cholesterol and cold cholesterol in 10% Intralipid(R) was immediately administered orally to the animals. Systemic blood was sampled and the concentration of cholesterol in plasma was determined by means of radioactivity. Protonation of NSAS using an ion-exchange column resulted in significant inhibition of cholesterol absorption relative to the control group (31.5% and 38.6% reduction in absorption of cholesterol for 50 and 100 mg/kg doses, respectively). Other surface-ion modifications of NSAS compounds did not show significant effect on intestinal cholesterol absorption. The inhibition of cholesterol absorption by ezetimibe was superior and by stigmastanol was equal to the effect of protonated NSAS in the doses investigated in this study. In conclusion, protonated NSAS material seems to inhibit significantly the intestinal absorption of dietary cholesterol in a rat model. PMID:19090562

  13. Intestinal Na+/glucose cotransporter expressed in Xenopus oocytes is electrogenic.

    PubMed Central

    Umbach, J A; Coady, M J; Wright, E M

    1990-01-01

    The cloned rabbit intestinal Na+/glucose cotransporter was expressed in Xenopus oocytes, and transmembrane currents associated with this transporter were monitored using a two-electrode voltage clamp. Addition of D-glucose to a Na(+)-containing solution bathing these oocytes generated a current which was blocked by phlorizin. Water-injected control oocytes did not exhibit any currents under these conditions. The magnitude and shape of the currents were dependent on the extracellular glucose and Na+ concentrations and the membrane potential. At Vhold = -50 mV, the Km values for glucose and Na+ were 14 +/- 2 (N = 4) microM and 17 +/- 1 (N = 3) mM, respectively. These Km values and imax exhibited voltage dependence: increasing the membrane potential from -30 to -150 mV increased KGlcm and imax threefold and decreased KNam eightfold. The reversal potential (VR) of the phlorizin-sensitive, glucose-dependent current varied with log Nao+ (slope 46 +/- 6 [N = 9] mV). In the absence of sugar, a Na(+)-dependent, phlorizin-sensitive (Ki = 3 +/- 0.5 microM) current was detected only in RNA-injected oocytes. The amplitude of this current at -50 mV was 6 +/- 1% (N = 13) of the maximum current measured in the presence of D-glucose. The VR of this sugar-independent current varied with log Nao+ (slope 63 +/- 1 [N = 4] mV), indicating that the cotransporter may carry Na+ in the absence of sugar. We conclude that the Na+/glucose cotransporter is electrogenic and that investigations of currents associated with its operation can yield valuable insights into the mechanisms of solute translocation. PMID:1697483

  14. 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. PMID:22425566

  15. Absorption of glucose polymers from canine jejunum deprived of pancreatic amylase.

    PubMed

    Kerzner, B; Sloan, H R; McClung, H J; Chidi, C C; Ailabouni, A H; Seckel, C

    1986-06-01

    We evaluated the absorption of glucose polymers in canine jejunal Thiry-Vella fistulas proven to be free of pancreatic amylase. Medium-length oligomers with degrees of polymerization of 6 through 10 glucose units (DP 6-10) and long-chain material (DPavg23) were isolated from a cornstarch hydrolysate. We perfused 90, 180, and 360 mg/dl solutions of glucose, DP 6-10, and DPavg23 at 0.4, 1.9, and 3.4 ml/min. At all perfusion rates carbohydrate absorption decreased as the chain length of the oligomers increased, and these differences persisted even at the slowest perfusion rate employed. In two additional animals the fistulas were perfused at 3.4 ml/min with the three test carbohydrates at concentrations of 90, 180, 225, 270, 315, 360, 405, and 450 mg/dl. At this flow rate, the assimilative process of DP 6-10 and the long-chain fraction appeared to be saturated at carbohydrate concentrations above 360 mg/dl, whereas the absorption of glucose was linearly related to concentration throughout the range studied. With both groups of polymers, the fluid emerging from the fistula was virtually free of glucose, a finding that suggests that polymer digestion, not glucose absorption, is the rate-limiting step for polymer assimilation. PMID:2424320

  16. [Intestinal absorption of aloe-emodin using single-passintestinal perfusion method in rat].

    PubMed

    Wang, Jinrong; Wang, Ping; Yang, Yongmao; Meng, Xianli; Zhang, Yan

    2011-09-01

    The intestinal absorption of aloe-emodin was investigated using the single pass intestinal perfusion (SPIP) technique in S/D rats. SPIP was performed in each isolated segment of the intestine (i.e., duodenum, jejunum, ileum and colon) and the different concentrations inhibitor group of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP2) with the concentrations of aloe-emodin (0.238 mg x L(-1)) at a flow rate of 0.28 mL x min(-1). The effective absorption rate constant (Ka) and apparent absorption coefficient (Papp) of aloe-emodin for each segment were determined before and after treated with different concentrations of inhibitors of P-gp and MRP2 respectively. Aloe-emodin exhibits a high intestinal permeability except the the ileum, indicative that the compounds are well absorbed. Decreases of Ka and Papp values in the duodenum, jejunum, colon and ileum, furthermore, the duodenum has significant increased compared with the ileum, there are have no significant difference in other isolated region of the intestine. Compared with the group which have no inhibitor of P-gp, the Ka and Papp were significantly increased in inhibitor of P-gp groups. Compared with the group of no inhibitor of MRP2, the Ka and Papp were significantly increased in inhibitor of MRP2 groups with the highest and the middle concentration. The results suggested that the inhibitors of P-gp and MRP2 all can promote the intestinal absorption of aloe-emodin. PMID:22121810

  17. Intestinal radiocalcium absorption in the goat: measurement by a double-isotope technique.

    PubMed

    Hove, K

    1984-01-01

    Intestinal radiocalcium absorption was measured in goats by a double-isotope technique involving injection of 45CaCl2 intravenously and 47CaCl2 into the abomasum. Cumulative absorption of radiocalcium was calculated by deconvolution analysis form curves of plasma radioactivity. Repeated measurements at 2 d intervals gave highly reproducible results (r 0.94, P less than 0.001). No systematic difference between two consecutive measurements was observed. A good agreement between absorption of radiocalcium from simultaneously administered 47CaCl2 and 45Ca-labelled hay (r 0.93, P less than 0.001) seems to justify the use of inorganic 47Ca as a tracer for Ca in ruminant diets. Two- to three-fold increases in radiocalcium absorption 48 h after oral treatment with 1,25-dihydroxycholecalciferol or leaves of Solanum malacoxylon showed the usefulness of the method in situations of rapidly changing Ca absorption. Endogenous adaptations in intestinal radiocalcium absorption from 20 to 43% were observed in lactating goats when Ca intakes decreased from 12 to 4 g/d. It is concluded that the double-isotope technique is a suitable method for studies of Ca absorption in ruminants when tracer is introduced into the abomasum. The test is completed in 3-4 h and may therefore be used in situations where the absorption of Ca undergoes rapid changes. PMID:6546295

  18. Intestinal absorption of an arginine-containing peptide in cystinuria

    PubMed Central

    Asatoor, A. M.; Harrison, B. D. W.; Milne, M. D.; Prosser, D. I.

    1972-01-01

    Separate tolerance tests involving oral intake of the dipeptide, L-arginyl-L-aspartate, and of a corresponding free amino acid mixture, were carried out in a single type 2 cystinuric patient. Absorption of aspartate was within normal limits, whilst that of arginine was normal after the peptide but considerably reduced after the amino acid mixture. The results are compared with the increments of serum arginine found in eight normal subjects after the oral intake of the free amino acid mixture. Analyses of urinary pyrrolidine and of tetramethylenediamine in urine samples obtained after the two tolerance tests in the patient support the view that arginine absorption was subnormal after the amino acid mixture but within normal limits after the dipeptide. PMID:5045711

  19. Phosphorylation of RS1 (RSC1A1) Steers Inhibition of Different Exocytotic Pathways for Glucose Transporter SGLT1 and Nucleoside Transporter CNT1, and an RS1-Derived Peptide Inhibits Glucose Absorption.

    PubMed

    Veyhl-Wichmann, Maike; Friedrich, Alexandra; Vernaleken, Alexandra; Singh, Smriti; Kipp, Helmut; Gorboulev, Valentin; Keller, Thorsten; Chintalapati, Chakravarthi; Pipkorn, Rüdiger; Pastor-Anglada, Marçal; Groll, Jürgen; Koepsell, Hermann

    2016-01-01

    Cellular uptake adapts rapidly to physiologic demands by changing transporter abundance in the plasma membrane. The human gene RSC1A1 codes for a 67-kDa protein named RS1 that has been shown to induce downregulation of the sodium-D-glucose cotransporter 1 (SGLT1) and of the concentrative nucleoside transporter 1 (CNT1) in the plasma membrane by blocking exocytosis at the Golgi. Injecting RS1 fragments into Xenopus laevis oocytes expressing SGLT1 or CNT1 and measuring the expressed uptake of α-methylglucoside or uridine 1 hour later, we identified a RS1 domain (RS1-Reg) containing multiple predicted phosphorylation sites that is responsible for this post-translational downregulation of SGLT1 and CNT1. Dependent on phosphorylation, RS1-Reg blocks the release of SGLT1-containing vesicles from the Golgi in a glucose-dependent manner or glucose-independent release of CNT1-containing vesicles. We showed that upregulation of SGLT1 in the small intestine after glucose ingestion is promoted by glucose-dependent disinhibition of the RS1-Reg-blocked exocytotic pathway of SGLT1 between meals. Mimicking phosphorylation of RS1-Reg, we obtained a RS1-Reg variant that downregulates SGLT1 in the brush-border membrane at high luminal glucose concentration. Because RS1 mediates short-term regulation of various transporters, we propose that the RS1-Reg-navigated transporter release from Golgi represents a basic regulatory mechanism of general importance, which implies the existence of receptor proteins that recognize different phosphorylated forms of RS1-Reg and of complex transporter-specific sorting in the trans-Golgi. RS1-Reg-derived peptides that downregulate SGLT1 at high intracellular glucose concentrations may be used for downregulation of glucose absorption in small intestine, which has been proposed as strategy for treatment of type 2 diabetes. PMID:26464324

  20. 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

  1. Intestinal absorption of aloin, aloe-emodin, and aloesin; A comparative study using two in vitro absorption models

    PubMed Central

    Park, Mi-Young; Kwon, Hoon-Jeong

    2009-01-01

    Aloe products are one of the top selling health-functional foods in Korea, however the adequate level of intake to achieve desirable effects are not well understood. The objective of this study was to determine the intestinal uptake and metabolism of physiologically active aloe components using in vitro intestinal absorption model. The Caco-2 cell monolayer and the everted gut sac were incubated with 5-50 µM of aloin, aloe-emodin, and aloesin. The basolateral appearance of test compounds and their glucuronosyl or sulfated forms were quantified using HPLC. The % absorption of aloin, aloe-emodin, and aloesin was ranged from 5.51% to 6.60%, 6.60% to 11.32%, and 7.61% to 13.64%, respectively. Up to 18.15%, 18.18%, and 38.86% of aloin, aloe-emodin, and aloesin, respectively, was absorbed as glucuronidated or sulfated form. These results suggest that a significant amount is transformed during absorption. The absorption rate of test compounds except aloesin was similar in two models; more aloesin was absorbed in the everted gut sac than in the Caco-2 monolayer. These results provide information to establish adequate intake level of aloe supplements to maintain effective plasma level. PMID:20016696

  2. 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. PMID:24769669

  3. Effect of absorption of D-glucose and water on paracellular transport in rat duodenum-jejunum.

    PubMed

    O'Rourke, M; Shi, X; Gisolfi, C; Schedl, H

    1995-03-01

    Paracellular transport is thought to be a major absorptive pathway for small nutrient molecules. The authors used in vivo in situ perfusion of rat duodenum-proximal jejunum to examine paracellular transport using lactulose as a probe. They perfused solutions with a constant lactulose concentration but varied initial D-glucose concentration (range 12-176 mM) to open paracellular pathways and to increase water absorption, thereby optimizing potential for paracellular transport of lactulose and other solutes in its molecular weight range. All solutions contained sodium chloride to approach isotonicity. Water absorption was measured as the difference in weight of solution perfused and sample collected. Absorption of D-glucose increased with mean luminal D-glucose concentration, and water absorption more than doubled (from 0.12 +/- 0.03 to 0.26 +/- 0.05 mL/min per g dry wt of segment) as mean luminal glucose concentration was increased from 10 to 80 mM. Lactulose absorption was at the threshold of detection and did not correlate with D-glucose or water absorption. Expressed as percent per segment, D-glucose absorption ranged from 29-50%, and the lactulose absorption rate was 4-5%. The fraction of D-glucose absorption that could be attributed to lactulose absorptive pathways was 12% at the highest rate of water absorption. In conclusion, based on lactulose as a probe, under conditions of opening tight junctions by D-glucose, the paracellular component of D-glucose absorption was of the order of 1/10 of total D-glucose absorption (ie, not a major absorptive pathway. PMID:7879819

  4. Intestinal absorption and biological effects of orally administered amorphous silica particles

    PubMed Central

    2014-01-01

    Although amorphous silica nanoparticles are widely used in the production of food products (e.g., as anticaking agents), there is little information available about their absorption and biological effects after oral exposure. Here, we examined the in vitro intestinal absorption and in vivo biological effects in mice of orally administered amorphous silica particles with diameters of 70, 300, and 1,000 nm (nSP70, mSP300, and mSP1000, respectively) and of nSP70 that had been surface-modified with carboxyl or amine groups (nSP70-C and nSP70-N, respectively). Analysis of intestinal absorption by means of the everted gut sac method combined with an inductively coupled plasma optical emission spectrometer showed that the intestinal absorption of nSP70-C was significantly greater than that of nSP70. The absorption of nSP70-N tended to be greater than that of nSP70; however, the results were not statistically significant. Our results indicate that silica nanoparticles can be absorbed through the intestine and that particle diameter and surface properties are major determinants of the degree of absorption. We also examined the biological effects of the silica particles after 28-day oral exposure in mice. Hematological, histopathological, and biochemical analyses showed no significant differences between control mice and mice treated with the silica particles, suggesting that the silica nanoparticles evaluated in this study are safe for use in food production. PMID:25288919

  5. Selenium-mercury interaction during intestinal absorption of /sup 75/Se compounds in chicks

    SciTech Connect

    Mykkaenen, H.M.M.; Metsaeniitty, L.

    1987-08-01

    The effects of inorganic (HgCl/sub 2/) and organic (CH/sub 3/HgCl) mercury on the intestinal absorption of Se compounds (Na/sub 2/(75)SeO/sub 3/, Na/sub 2/(75)SeO4, L-(/sup 75/Se)methionine ((/sup 75/Se)Met)) were determined in 3-wk-old White Leghorn cockerels by the in vivo ligated duodenal loop procedure. The intraduodenal dose contained 0.05 microCi /sup 75/Se, 0.01 mM Se, 150 mM NaCl and 0-1.0 mM Hg. In the presence of 1 mM inorganic Hg in the intraduodenal dose, the absorption of the inorganic /sup 75/Se compounds was only about 65% of that in the control group, whereas only a slight inhibitory effect on (/sup 75/Se)Met absorption was observed. Methylmercury had no effect on (/sup 75/Se)selenite absorption. Precipitation of the /sup 75/Se-selenite in the intestinal lumen partly explained the direct interaction between inorganic Hg and Se compounds. Absorption of (/sup 75/Se)Met and (/sup 75/Se)selenite was also determined in chicks fed after hatching a purified diet supplemented with varying amounts of Hg (0-500 mg/kg) and Se (0-4 mg/kg). Dietary Hg significantly reduced the transfer of (/sup 75/Se)selenite to body by enhancing the accumulation of the isotope in the intestinal tissue. Dietary Hg did not affect the absorption of (/sup 75/Se)Met, but altered the whole-body distribution of this Se compound. Because interaction between Se and Hg was observed mainly between the inorganic compounds and with use of a manyfold excess of Hg over Se, the data suggest that intestinal interaction between these metals is not of great nutritional importance.

  6. 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

  7. What kinds of substrates show P-glycoprotein-dependent intestinal absorption? Comparison of verapamil with vinblastine.

    PubMed

    Ogihara, Takuo; Kamiya, Masatsugu; Ozawa, Makoto; Fujita, Takuya; Yamamoto, Akira; Yamashita, Shinji; Ohnishi, Shuhei; Isomura, Yasuo

    2006-06-01

    The influence of P-glycoprotein (P-gp) on intestinal absorption of drugs was investigated by comparison of the uptakes of two P-gp substrates, verapamil and vinblastine, using intestinal segments of wild-type and mdr1a/1b gene-deficient (mdr1a/1b(-/-)) mice, and Caco-2 cells. When [(3)H]vinblastine was injected into intestinal segments of wild-type mice, vinblastine was absorbed from duodenum and ileum, but not from jejunum. This difference among intestinal regions could not be explained by segmental differences of mdr1a mRNA expression. In Caco-2 cells, it was found that vinblastine had a high value of efflux/influx ratio (an index of affinity for P-gp) of 12.1, and a low permeability of less than 1 x 10(-6) cm/sec. The corresponding values for verapamil were 4.9 and 10.6 x 10(-6) cm/sec, respectively. After oral administration of [(3)H]vinblastine to mice, the maximum concentration (C(max)) and the area under the plasma concentration time-curve from time 0 to 24 hr (AUC(0-24 hr)) for mdr1a/1b(-/-) mice were 1.5 times greater than those for wild-type mice, while these parameters were not significantly different between the two strains in the case of [(3)H]verapamil. Therefore, P-gp substrates may be classified into at least two types, i.e., verapamil-type, for which the intestinal absorption is unaffected by P-gp, and vinblastine-type, for which the intestinal absorption is influenced by P-gp. Vinblastine-type P-gp substrates, with low permeability and high affinity for P-gp, would be unfavorable candidates for oral drugs. PMID:16858128

  8. LXR driven induction of HDL-cholesterol is independent of intestinal cholesterol absorption and ABCA1 protein expression.

    PubMed

    Kannisto, Kristina; Gåfvels, Mats; Jiang, Zhao-Yan; Slätis, Katharina; Hu, Xiaoli; Jorns, Carl; Steffensen, Knut R; Eggertsen, Gösta

    2014-01-01

    We investigated whether: (1) liver X receptor (LXR)-driven induction of high-density lipoprotein cholesterol (HDL-C) and other LXR-mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL-C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP-binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down-regulation of intestinal Niemann-Pick C1-like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL-C and ApoAI levels. GW3965 also increased Apoa1 mRNA levels in primary mouse hepatocytes and HEPA1-6 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL-C or ApoAI levels. Thus, the LXR-driven induction of HDL-C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and/or low levels of intracellular cholesterol prevented post-transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol. PMID:24163219

  9. 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

  10. 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

  11. 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.

  12. Intestinal fluid absorption in anadromous salmonids: importance of tight junctions and aquaporins

    PubMed Central

    Sundell, Kristina S.; Sundh, Henrik

    2012-01-01

    The anadromous salmonid life cycle includes both fresh water (FW) and seawater (SW) stages. The parr-smolt transformation (smoltification) pre-adapt the fish to SW while still in FW. The osmoregulatory organs change their mode of action from a role of preventing water inflow in FW, to absorb ions to replace water lost by osmosis in SW. During smoltification, the drinking rate increases, in the intestine the ion and fluid transport increases and is further elevated after SW entry. In SW, the intestine absorbs ions to create an inwardly directed water flow which is accomplished by increased Na+, K+-ATPase (NKA) activity in the basolateral membrane, driving ion absorption via ion channels and/or co-transporters. This review will aim at discussing the expression patterns of the ion transporting proteins involved in intestinal fluid absorption in the FW stage, during smoltification and after SW entry. Of equal importance for intestinal fluid absorption as the active absorption of ions is the permeability of the epithelium to ions and water. During the smoltification the increase in NKA activity and water uptake in SW is accompanied by decreased paracellular permeability suggesting a redirection of the fluid movement from a paracellular route in FW, to a transcellular route in SW. Increased transcellular fluid absorption could be achieved by incorporation of aquaporins (AQPs) into the enterocyte membranes and/or by a change in fatty acid profile of the enterocyte lipid bilayer. An increased incorporation of unsaturated fatty acids into the membrane phospholipids will increase water permeability by enhancing the fluidity of the membrane. A second aim of the present review is therefore to discuss the presence and regulation of expression of AQPs in the enterocyte membrane as well as to discuss the profile of fatty acids present in the membrane phospholipids during different stages of the salmonid lifecycle. PMID:23060812

  13. 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. PMID:27055721

  14. Enhancing the intestinal absorption of poorly water-soluble weak-acidic compound by controlling local pH.

    PubMed

    Iwanaga, Kazunori; Kato, Shino; Miyazaki, Makoto; Kakemi, Masawo

    2013-12-01

    Recently, the number of poorly water-soluble drug candidates has increased and has hindered the rapid improvement of new drugs with low intestinal absorption; however, the intestinal absorption of pH-dependent poorly water-soluble compounds is expected to be markedly improved by changing the pH in the vicinity of the absorption site. The aim of this study is to clarify the effect of local pH change in the intestinal tract by magnesium oxide on the intestinal absorption of hydrochlorothiazide, a model poorly water-soluble weak-acid compound. The application of hydrochlorothiazide granule containing magnesium oxide to the rat intestinal loop increased the pH in the vicinity of the dosing site to more than 8.5 for 90 min without any mucosal damage. As a result, absorption of hydrochlorothiazide increased by the addition of magnesium oxide to the granule. Intraintestinal administration of a suspension prepared from hydrochlorothiazide granules with magnesium oxide increased the intestinal absorption and the AUC value was 3-fold higher than that without magnesium oxide. To further increase the intestinal absorption of hydrochlorothiazide, we prepared granules containing magnesium oxide and chitosan as a mucoadhesive and tight junction opening material. Chitosan showed a marked increase of intestinal absorption, and the AUC value after the administration of suspensions of chitosan granules was more than 5-fold higher than that of granules containing hydrochlorothiazide alone, respectively. In summary, it has been clarified that the intestinal absorption of weak-acidic poorly water-soluble compound can be enhanced by increasing local pH, mucoadhesion and opening tight junction. PMID:22443480

  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. Proliferation and mRNA expression of absorptive villous cell markers and mineral transporters in prolactin-exposed IEC-6 intestinal crypt cells.

    PubMed

    Teerapornpuntakit, Jarinthorn; Wongdee, Kannikar; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-06-01

    During pregnancy and lactation, prolactin (PRL) enhances intestinal absorption of calcium and other minerals for fetal development and milk production. Although an enhanced absorptive efficiency is believed to mainly result from the upregulation of mineral transporters in the absorptive villous cells, some other possibilities, such as PRL-enhanced crypt cell proliferation and differentiation to increase the absorptive area, have never been ruled out. Here, we investigated cell proliferation and mRNA expression of mineral absorption-related genes in the PRL-exposed IEC-6 crypt cells. As expected, the cell proliferation was not altered by PRL. Inasmuch as the mRNA expressions of villous cell markers, including dipeptidylpeptidase-4, lactase and glucose transporter-5, were not increased, PRL was not likely to enhance crypt cell differentiation into the absorptive villous cells. In contrast to the previous findings in villous cells, PRL was found to downregulate the expression of calbindin-D(9k), claudin-3 and occludin in IEC-6 crypt cells, while having no effect on transient receptor potential vanilloid family channels-5/6, plasma membrane Ca(2+)-ATPase (PMCA)-1b and Na(+)/Ca(2+) exchanger-1 expression. In conclusion, IEC-6 crypt cells did not respond to PRL by increasing proliferation or differentiation into villous cells. The present results thus supported the previous hypothesis that PRL enhanced mineral absorption predominantly by increasing transporter expression and activity in the absorptive villous cells. PMID:22281785

  17. The effect of dietary protein on intestinal calcium absorption in rats.

    PubMed

    Gaffney-Stomberg, Erin; Sun, Ben-hua; Cucchi, Carrie E; Simpson, Christine A; Gundberg, Caren; Kerstetter, Jane E; Insogna, Karl L

    2010-03-01

    Increasing dietary protein intake in humans acutely increases urinary calcium. Isotopic absorption studies have indicated that, at least in the short term, this is primarily due to increased intestinal Ca absorption. To explore the mechanisms underlying dietary protein's effect on intestinal Ca absorption, female Sprague Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7 d, and Ca balance was measured during d 4-7. On d 7, duodenal mucosa was harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the 40% protein diet both absorbed and retained more Ca compared with the 5% protein group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively; P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high-protein diet. Maximum velocity (V(max)) was higher in the BBMVs prepared from the high-protein group compared with those from the low-protein group (90 vs. 36 nmol Ca/mg protein x min, P < 0.001; 95% CI: 46-2486 and 14-55, respectively). The Michaelis Menten constant (K(m)) was unchanged (2.2 mm vs. 1.8 mm, respectively; P = 0.19). We conclude that in rats, as in humans, acute increases in protein intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV Ca uptake studies suggest that higher protein intake improves Ca absorption, at least in part, by increasing transcellular Ca uptake. PMID:20147526

  18. The Effect of Dietary Protein on Intestinal Calcium Absorption in Rats

    PubMed Central

    Gaffney-Stomberg, Erin; Sun, Ben-hua; Cucchi, Carrie E.; Simpson, Christine A.; Gundberg, Caren; Kerstetter, Jane E.; Insogna, Karl L.

    2010-01-01

    Increasing dietary protein intake in humans acutely increases urinary calcium. Isotopic absorption studies have indicated that, at least in the short term, this is primarily due to increased intestinal Ca absorption. To explore the mechanisms underlying dietary protein’s effect on intestinal Ca absorption, female Sprague Dawley rats were fed a control (20%), low (5%), or high (40%) protein diet for 7 d, and Ca balance was measured during d 4–7. On d 7, duodenal mucosa was harvested and brush border membrane vesicles (BBMVs) were prepared to evaluate Ca uptake. By d 7, urinary calcium was more than 2-fold higher in the 40% protein group compared with control (4.2 mg/d vs. 1.7 mg/d; P < 0.05). Rats consuming the 40% protein diet both absorbed and retained more Ca compared with the 5% protein group (absorption: 48.5% vs. 34.1% and retention: 45.8% vs. 33.7%, respectively; P < 0.01). Ca uptake was increased in BBMVs prepared from rats consuming the high-protein diet. Maximum velocity (Vmax) was higher in the BBMVs prepared from the high-protein group compared with those from the low-protein group (90 vs. 36 nmol Ca/mg protein · min, P < 0.001; 95% CI: 46–2486 and 14–55, respectively). The Michaelis Menten constant (Km) was unchanged (2.2 mm vs. 1.8 mm, respectively; P = 0.19). We conclude that in rats, as in humans, acute increases in protein intake result in hypercalciuria due to augmented intestinal Ca absorption. BBMV Ca uptake studies suggest that higher protein intake improves Ca absorption, at least in part, by increasing transcellular Ca uptake. PMID:20147526

  19. 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.

  20. Involvement of intestinal uptake transporters in the absorption of azithromycin and clarithromycin in the rat.

    PubMed

    Garver, Eric; Hugger, Erin D; Shearn, Shawn P; Rao, Anuradha; Dawson, Paul A; Davis, Charles B; Han, Chao

    2008-12-01

    Macrolide antibiotics azithromycin (AZI) and clarithromycin (CLARI) are large molecular weight compounds and are substrates for apically polarized efflux transporters such as P-glycoprotein, which can potentially restrict intestinal absorption. However, despite these undesired physicochemical and biopharmaceutical properties, AZI and CLARI exhibit moderate to excellent p.o. bioavailability in preclinical species and humans. Intestinal uptake transporters, such as organic anion transporting polypeptides (OATPs), can facilitate the uptake of drugs that are substrates and hence increase p.o. absorption. The present study was designed to determine whether the intestinal Oatps are involved in absorption of these macrolides. AZI or CLARI was dosed p.o. to Sprague-Dawley rats after p.o. administration with vehicle or rifamycin SV (RIF), an OATP inhibitor. The p.o. exposures of AZI and CLARI were reduced 65 and 45%, respectively, when coadministered with an optimized RIF regimen. The p.o. RIF had no affect on the total blood clearance of these macrolides and most likely did not cause induction of metabolizing enzymes and/or transporters. Therefore, the results suggest that inhibition of an RIF-sensitive uptake transporter such as Oatp along the rat gastrointestinal tract was responsible for reduced p.o. exposure of AZI and CLARI. In addition, AZI and CLARI caused inhibition of taurocholate uptake in rat Oatp1a5-transfected Madin-Darby canine kidney cell monolayers. The in vitro and in vivo results suggest that the intestinal Oatps are involved in the p.o. absorption of AZI and CLARI in the rat. PMID:18755851

  1. 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.

  2. 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

  3. 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. PMID:24336247

  4. 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.

  5. Effect of the Artificial Sweetener, Acesulfame Potassium, a Sweet Taste Receptor Agonist, on Glucose Uptake in Small Intestinal Cell Lines

    PubMed Central

    Zheng, Ye; Sarr, Michael G.

    2012-01-01

    Sweet taste receptors may enhance glucose absorption. AIM To explore the cell biology of sweet taste receptors on glucose uptake. HYPOTHESIS Artificial sweeteners increase glucose uptake via activating sweet taste receptors in the enterocyte to translocate GLUT2 to the apical membrane through the PLC βII pathway. METHODS Caco-2, RIE-1, and IEC-6 cells, starved from glucose for 1 h were pre-incubated with 10 mM acesulfame potassium (AceK). Glucose uptake was measured by incubating cells for 1 to 10 min with 0.5–50 mM glucose with or without U-73122, chelerythrine, and cytochalasin B. RESULTS In Caco-2 and RIE-1 cells, 10 mM AceK increased glucose uptake by 20~30% at glucose ≥ 25 mM, but not in lesser glucose concentrations (≤10 mM), nor at 1 min or 10 min incubations. U-73122 inhibited uptake at glucose ≥ 25 mM and for 5 min incubation; chelerythrine and cytochalasin B had similar effects. No effect occurred in IEC-6 cells. SUMMARY Activation of sweet taste receptors had no effect on glucose uptake in low (<25 mM) glucose concentrations but increased uptake at greater concentrations (≥ 25 mM). CONCLUSIONS Role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself. PMID:22948835

  6. Resistin-like molecule α decreases glucose tolerance during intestinal inflammation1

    PubMed Central

    Munitz, Ariel; Seidu, Luqman; Cole, Eric T; Ahrens, Richard; S, Simon P Hogan; Rothenberg, Marc E

    2008-01-01

    Resistin-like molecule α (Relm-α), is a secreted cysteine-rich protein belonging to a newly defined family of proteins including resistin, Relm-β and Relm-γ. Resistin was initially defined based on its insulin resistance activity, but the family members are highly upregulated in various inflammatory states, especially those involving intestinal inflammation. Herein, we report the role of Relm-α at baseline and following an experimental model of colitis. Relm-α was readily detected in the serum at baseline (4−5 ng/ml) and its level was regulated by energy uptake. Retnla−/− mice had decreased baseline circulating leptin levels but displayed normal glucose, glucose clearance and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a non-redundant pro-inflammatory role for Relm-α was uncovered as Retnla−/− mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-α regulated eosinophil-directed cytokines (e.g. IL-5, CCL11/eotaxin-1 and CCL5/RANTES) ex vivo. Consistently, DSS-treated Retnla−/− mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NFκB, ERK1/2 and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-α was upregulated and DSS-treated Retnla−/− mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla−/− mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS-treatment. These findings demonstrate a central pro-inflammatory role for Relm-α in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance and energy intake. PMID:19201890

  7. 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

  8. 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. PMID:25690454

  9. Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse.

    PubMed

    Wang, David Q-H; Tazuma, Susumu; Cohen, David E; Carey, Martin C

    2003-09-01

    We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; alpha-, beta-, or omega-muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro-beta-muricholate (42 +/- 6%) and taurocholate (50 +/- 7%) with a hydrophobicity index of -0.35 +/- 0.04 produced cholesterol absorption of 37 +/- 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic beta-muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural alpha- and beta-muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans. PMID:12748061

  10. 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

  11. Glucose-6-phosphate dehydrogenase in small intestine of rabbit: biochemical properties and subcellular localization.

    PubMed

    Ninfali, P; Malatesta, M; Biagiotti, E; Aluigi, G; Gazzanelli, G

    2001-07-01

    Biochemical properties and cellular and subcellular distribution patterns of glucose-6-phosphate dehydrogenase (G6PD) were investigated in small intestine of rabbits. The specific activity of G6PD in fresh homogenates of small intestine was 19 +/- 9 IU/g protein. This value did not change significantly after dialysis. The kinetic and electrophoretic properties of the partially purified enzyme were similar to those found in other rabbit tissues. Enzyme histochemical analysis of G6PD activity using the tetrazolium salt method showed high activity in epithelial cells of villi and crypts of Lieberkuhn. The activity in acinar cells of Brunner's glands was lower than that in epithelium, whereas cells of the muscularis externa showed a very low activity. Immunohistochemical analysis showed that the amounts of G6PD protein were lower in the epithelium than in Brunner's glands and muscularis externa. The differences between distribution patterns of activity and protein of G6PD may reflect the presence of inactive enzyme molecules in Brunner's glands and muscularis externa or posttranslational activation of G6PD in epithelium. Electron microscopic immunocytochemical analysis performed with gold-labelled antibodies showed the presence of G6PD protein throughout the cytoplasm and at smooth endoplasmic reticulum in enterocytes. In Paneth cells and cells of Brunner's glands, G6PD was found in the cytoplasm, at rough endoplasmic reticulum and Golgi complex. Immunolabelling was not found in mitochondria or nuclei. Our findings show that G6PD is heterogeneously distributed in cells of the small intestine and that the enzyme is associated with rough and smooth endoplasmic reticulum to support synthetic functions in these compartments by NADPH production. PMID:11482375

  12. Proliposome powders for enhanced intestinal absorption and bioavailability of raloxifene hydrochloride: effect of surface charge.

    PubMed

    Velpula, Ashok; Jukanti, Raju; Janga, Karthik Yadav; Sunkavalli, Sharath; Bandari, Suresh; Kandadi, Prabhakar; Veerareddy, Prabhakar Reddy

    2013-12-01

    The primary goal of the present study was to investigate the combined prospective of proliposomes and surface charge for the improved oral delivery of raloxifene hydrochloride (RXH). Keeping this objective, the present systematic study was focused to formulate proliposomes by varying the ratio of hydrogenated soyphosphatidylcholine and cholesterol. Furthermore, to assess the role of surface charge on improved absorption of RXH, anionic and cationic vesicles were prepared using dicetyl phosphate and stearylamine, respectively. The formulations were characterized for size, zeta potential and entrapment efficiency. The improved dissolution characteristics assessed from dissolution efficiency, mean dissolution rate were higher for proliposome formulations. The solid state characterization studies indicate the transformation of native crystalline form of the drug to amorphous and/or molecular state. The higher effective permeability coefficient and fraction absorbed in humans extrapolated from in situ single-pass intestinal absorption study data in rats provide an insight on the potential of proliposomes and cationic surface charge for augment in absorption across gastro intestinal barrier. To draw the conclusions, in vivo pharmacokinetic study carried out in rats indicate a threefold enhancement in the rate and extent of absorption of RXH from cationic proliposome formulation which unfurl the potential of proliposomes and role of cationic charge for improved oral delivery of RXH. PMID:22458264

  13. Melatonin not only restores but also prevents the inhibition of the intestinal Ca(2+) absorption caused by glutathione depleting drugs.

    PubMed

    Areco, Vanessa; Rodriguez, Valeria; Marchionatti, Ana; Carpentieri, Agata; Tolosa de Talamoni, Nori

    2016-07-01

    We have previously demonstrated that melatonin (MEL) blocks the inhibition of the intestinal Ca(2+) absorption caused by menadione (MEN). The purpose of this study were to determine whether MEL not only restores but also prevents the intestinal Ca(2+) absorption inhibited either by MEN or BSO, two drugs that deplete glutathione (GSH) in different ways, and to analyze the mechanisms by which MEN and MEL alter the movement of Ca(2+) across the duodenum. To know this, chicks were divided into four groups: 1) controls, 2) MEN treated, 3) MEL treated, and 4) treated sequentially with MEN and MEL or with MEN and MEL at the same time. In a set of experiments, chicks treated with BSO or sequentially with BSO and MEL or with BSO and MEL at the same time were used. MEL not only restored but also prevented the inhibition of the chick intestinal Ca(2+) absorption produced by either MEN or BSO. MEN altered the protein expression of molecules involved in the transcellular as well as in the paracellular pathway of the intestinal Ca(2+) absorption. MEL restored partially both pathways through normalization of the O2(-) levels. The nitrergic system was not altered by any treatment. In conclusion, MEL prevents or restores the inhibition of the intestinal Ca(2+) absorption caused by different GSH depleting drugs. It might become one drug for the treatment of intestinal Ca(2+) absorption under oxidant conditions having the advantage of low or null side effects. PMID:26970583

  14. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  15. The effect of amino acids on the intestinal absorption of immunoglobulins in the neonatal rat

    PubMed Central

    Bamford, D. R.; Donnelly, H.

    1974-01-01

    An in vitro preparation of 10-day-old rat intestine was used to examine the absorption of a number of amino acids and immunoglobulins. Evidence was obtained for the active absorption of alanine, leucine, methionine, histidine and lysine, but not for aspartic acid. A selective absorption of the homologous molecule was found in experiments where 131I-labelled rat and bovine IgG were presented to the ileum in 10-minute incubations. The greater uptake of rat IgG was unrelated to the relative rates of catabolism of the two molecules. Although the uptake of rat IgG was unaffected by 100 mM concentrations of neutral and acidic amino acids, the basic amino acids arginine and lysine significantly stimulated uptake. PMID:4854740

  16. Effect of undernutrition and hormone treatments on the absorption of proteins in suckling rat intestine

    SciTech Connect

    Babbar, H.S.; Jaswal, V.M.; Mahmood, A. )

    1990-02-01

    The absorption of {sup 125}I-labeled BSA and gamma-globulin was significantly (P less than 0.01) elevated in UN pups compared to the controls. Administration of pharmacological doses of cortisone, thyroxine, and insulin markedly (P less than 0.001) reduced the absorption of BSA and gamma-globulin in UN pups. There was no significant difference in the binding of {sup 125}I-labeled BSA and gamma-globulin to microvillus membrane in the control and experimental animals. However, the degradation of labeled BSA and gamma-globulin by luminal content was considerably higher (55-70%) in controls compared to UN pups. This suggested that observed increase in the absorption of proteins in nutritionally deprived pups was unrelated to their binding to the microvillus surface but presumably it is a consequence of reduced luminal degradation together with delayed maturational development as suggested by the pattern of brush border enzymes in the UN intestinal tissue.

  17. Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1.

    PubMed

    Nässl, Anna-Maria; Rubio-Aliaga, Isabel; Fenselau, Henning; Marth, Mena Katharina; Kottra, Gabor; Daniel, Hannelore

    2011-07-01

    The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism. PMID:21350187

  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. 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

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

    PubMed

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

    2015-06-01

    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

  1. Translating Molecular Physiology of Intestinal Transport into Pharmacologic Treatment of Diarrhea: Stimulation of Na+ Absorption

    PubMed Central

    Singh, Varsha; Yang, Jianbo; Chen, Tiane-e; Zachos, Nick; Kovbasnjuk, Olga; Verkman, Alan; Donowitz, Mark

    2013-01-01

    Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing countries while representing an important cause of morbidity worldwide. The WHO recommended low osmolarity oral rehydration solutions plus zinc save lives in patients with acute diarrhea1, but there are no approved, safe drugs which have been shown to be effective against most causes of acute diarrhea. Identification of abnormalities in electrolyte handling by the intestine in diarrhea, including increased intestinal anion secretion and reduced Na+ absorption, suggest a number of potential drug targets. This is based on the view that successful drug therapy for diarrhea will result from correcting the abnormalities in electrolyte transport that are pathophysiologic for diarrhea. We review the molecular mechanisms of physiologic regulation of intestinal ion transport and changes that occur in diarrhea and the status of drugs being developed to correct the transport abnormalities in Na+ absorption which occur in diarrhea. Mechanisms of Cl− secretion and approaches to anti-Cl− secretory therapies of diarrhea are discussed in a companion review. PMID:24184676

  2. Translating molecular physiology of intestinal transport into pharmacologic treatment of diarrhea: stimulation of Na+ absorption.

    PubMed

    Singh, Varsha; Yang, Jianbo; Chen, Tiane-e; Zachos, Nicholas C; Kovbasnjuk, Olga; Verkman, Alan S; Donowitz, Mark

    2014-01-01

    Diarrheal diseases remain a leading cause of morbidity and mortality for children in developing countries, while representing an important cause of morbidity worldwide. The World Health Organization recommended that low osmolarity oral rehydration solutions plus zinc save lives in patients with acute diarrhea, but there are no approved, safe drugs that have been shown to be effective against most causes of acute diarrhea. Identification of abnormalities in electrolyte handling by the intestine in diarrhea, including increased intestinal anion secretion and reduced Na(+) absorption, suggest a number of potential drug targets. This is based on the view that successful drug therapy for diarrhea will result from correcting the abnormalities in electrolyte transport that are pathophysiologic for diarrhea. We review the molecular mechanisms of physiologic regulation of intestinal ion transport and changes that occur in diarrhea and the status of drugs being developed to correct the transport abnormalities in Na(+) absorption that occur in diarrhea. Mechanisms of Cl(-) secretion and approaches to anti-Cl(-) secretory therapies of diarrhea are discussed in a companion review. PMID:24184676

  3. Elucidation of the Intestinal Absorption Mechanism of Celastrol Using the Caco-2 Cell Transwell Model.

    PubMed

    Li, Hong; Li, Jie; Liu, Lu; Zhang, Yichuan; Luo, Yili; Zhang, Xiaoli; Yang, Peng; Zhang, Manna; Yu, Weifeng; Qu, Shen

    2016-08-01

    Celastrol, a triterpenoid isolated from stem (caulis) of Celastrus orbiculatus Thunb. (Celastraceae), has been known to have various pharmacological effects, including anti-inflammatory, anticancer, and antioxidant activities. However, the mechanism of the intestinal absorption of celastrol is unknown. The aim of this study was to investigate the intestinal absorption of celastrol using the Caco-2 cell transwell model. First, the bidirectional transport of celastrol in Caco-2 cell monolayers was observed. Then, the effects of time, concentration, temperature, paracellular pathway, and efflux transport inhibition on the transport of celastrol across the Caco-2 cell monolayers were investigated. The P-glycoprotein inhibitor verapamil and cyclosporin A, the multidrug resistance protein 2 inhibitor MK571, and the breast cancer resistance protein inhibitor reserpine were used. Additionally, the effects of celastrol on the activity of P-glycoprotein were evaluated using the rhodamine 123 uptake assay. In this study, we found that the intestinal transport of celastrol was a time- and concentration-dependent active transport. The paracellular pathway was not involved in the transport of celastrol, and the efflux of celastrol was energy dependent. The results indicated that celastrol is a substrate of P-glycoprotein but not multidrug resistance protein 2 or the breast cancer resistance protein. In addition, celastrol could not affect the uptake of rhodamine 123 in Caco-2 cells, which indicated that celastrol could not inhibit or induce the activity of P-glycoprotein. PMID:27159672

  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. Intestinal absorption of lithocholic acid sulfates in the rat: inhibitory effects of calcium

    SciTech Connect

    Kuipers, F.; Heslinga, H.; Havinga, R.; Vonk, R.J.

    1986-08-01

    Sulfation of lithocholic acid has been proposed as a mechanism for elimination of this hepatotoxic bile acid from the body by accelerating its fecal excretion. However, quantitative data on the absorption characteristics of sulfated lithocholic acid conjugates in vivo are scarce. We studied the intestinal absorption of /sup 14/C-labeled glycolithocholic acid (GLC), taurolithocholic acid (TLC), and their 3 alpha-sulfate esters, SGLC and STLC, respectively. Studies were performed in unanesthetized rats with a permanent biliary drainage. At an intestinal infusion rate of 125 nmol/min, which is comparable to 7% of the normal biliary bile acid output in the rat, the absorption of sulfated lithocholic acid conjugates was delayed when compared with their unsulfated precursors but quantitatively only slightly reduced over a 24-h period: SGLC 90.9 +/- 3.6%, GLC 94.4 +/- 1.1%, STLC 84.4 +/- 3.0%, and TLC 94.2 +/- 2.1%. Urinary excretion of sulfated and unsulfated bile acids was similar and never exceeded 2% of the dose. SGLC absorption was dose dependent, was not altered by coinfusion of rat bile, and was only slightly reduced by a sixfold overdose of taurocholic acid. SGLC and STLC were excreted into bile largely unchanged in form. In contrast, GLC and TLC were extensively metabolized to more polar bile acids, predominantly to beta-muricholic acid conjugates. Replacement of NaCl in the infusion fluid by CaCl2 reduced the absorption of SGLC and STLC by 63 and 52%, respectively. This calcium effect was less pronounced for the unsulfated bile acids: GLC -22%, and TL-19%. Absorption of taurocholic acid was unaffected by CaCL2.

  6. 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.

  7. Amino acid and peptide absorption from partial digests of proteins in isolated rat small intestine.

    PubMed Central

    Gardner, M L

    1978-01-01

    1. Absorption of each of sixteen amino acids, free and peptide-bound, has been measured in isolated rat small intestine perfused with five partial digests of proteins. 2. At low concentrations net absorption of each amino acid was proportional to its luminal concentration and independent of the nature of the amino acid. 3. A series of first-order multiple regressions was found to describe well the characteristics of absorption. 4. Rate constants for disappearance of free and peptide-bound amino acids from the lumen were closely similar. However, substantial back-flux occurred of amino acids derived from peptide hydrolysis. Hence 60-70% of the amino-N entering the serosal tissue fluid probably had left the lumen as free amino acids. 5. Intact peptides crossed the mucosa during absorption from a soy bean hydrolysate and in substantial quantities during absorption from one casein digest but not from another. With other hydrolysates there was no evidence for passage of peptides to the serosa. 6. In several cases there was a serious discrepancy between the amount of amino-N absorbed from the lumen and the amount accounted for as peptide or free amino acid in the serosal secretion. 7. The characteristics of absorption were similar (apart from the exceptions in 5 above) for all the digests studied except for soy bean hydrolysate. PMID:731590

  8. 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

  9. Use of laminar flow and unstirred layer models to predict intestinal absorption in the rat.

    PubMed Central

    Levitt, M D; Kneip, J M; Levitt, D G

    1988-01-01

    Carbon monoxide (CO) and [14C]warfarin were used to measure the preepithelial diffusion resistance resulting from poor luminal stirring (RL) in the constantly perfused rat jejunum at varying degrees of distension (0.05, 0.1, and 0.2 ml/cm). RL was much greater than epithelial cell resistance, indicating that poor stirring was the limiting factor in absorption and that an appropriate model of stirring should accurately predict absorption. A laminar flow model accurately predicted the absorption rate of both probes at all levels of gut distension, as well as the absorption of glucose when RL was the rate-limiting factor in absorption. In contrast, an unstirred layer model would not have predicted that gut distension would have little influence on absorption, and would have underestimated [14C]warfarin absorption relative to CO. We concluded that in the perfused rat jejunum, laminar flow accurately models luminal stirring and an unstirred layer should be considered to be a unit of resistance in laminar flow, rather than a model of luminal stirring. PMID:3366899

  10. 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

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

    PubMed

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

    2010-04-01

    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

  12. The Use of Low Molecular Weight Protamine Chemical Chimera to Enhance Monomeric Insulin Intestinal Absorption

    PubMed Central

    He, Huining; Sheng, Jianyong; David, Allan E.; Kwon, Young Min; Zhang, Jian; Huang, Yongzhuo; Wang, Jianxin; Yang, Victor C.

    2013-01-01

    Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a nontoxic yet potent cell penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogeneous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery. PMID:23863452

  13. 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.

  14. Preparation, characterization and in vitro intestinal absorption of a dry emulsion formulation containing atorvastatin calcium.

    PubMed

    Yin, Yong-Mei; Cui, Fu-De; Kim, Jung Sun; Choi, Min-Koo; Choi, Byung Chul; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2009-01-01

    A redispersible dry emulsion (DE) formulation of atorvastatin calcium (AC) was developed to enhance the in vitro dissolution of AC, thereby increasing its gastrointestinal absorption. The spray-drying technology was used where Plurol Oleique CC 497 was chosen as the oil phase. Effects of carriers, surfactants, and homogenizers on the characteristics of DE containing AC were systematically investigated. The final formulation consisted of dextrin and Poloxamer 188 as carrier and surfactant, respectively, and was homogenized by a high pressure homogenizer before spray drying. The in vitro release of AC from the optimized DE was significantly higher than that of pure AC powder (76% vs. 30% at 24 hr). The in vitro intestinal absorption of AC from the DE formulation was 0.77 microg/cm(2) at 2 hr, which was a 2.33-fold increase compared to the pure unformulated AC powder. These results suggest that the oral dry emulsion formulation could improve the intestinal absorption of AC. PMID:19555306

  15. 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. PMID:24158737

  16. 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...

  17. Regional intestinal absorption and biliary excretion of fluvastatin in the rat: possible involvement of mrp2.

    PubMed

    Lindahl, Anders; Sjöberg, Asa; Bredberg, Ulf; Toreson, Helena; Ungell, Anna-Lena; Lennernäs, Hans

    2004-01-01

    The first purpose of this study was to investigate the in vivo absorption, biliary secretion, and first-pass effect of fluvastatin following regional intestinal dosing in the rat. We also examined the membrane transport mechanisms and made in silico predictions of the relative importance of various intestinal regions to the human absorption of fluvastatin. Fluvastatin was administered intravenously (2, 10, and 20 micromol/kg) and into the duodenum (1.46, 2.92, 7.32, and 14.6 micromol/kg), jejunum (14.6 micromol/kg), ileum (1.46 and 14.6 mciromol/kg), and colon (1.46 and 14.6 micromol/kg) as a solution to conscious rats. In a separate group of rats, bile was collected after an i.v. dose of fluvastatin (2 micromol/kg). In the Caco-2 model the bidirectional transport of fluvastatin (16 microM) was investigated with and without various efflux inhibitors (verapamil, vinblastine, probenecid, and indomethacin, 160 microM). The human in vivo absorption of fluvastatin from an oral immediate release tablet and that from an oral extended release tablet (both 40 mg) were simulated in GastroPlus. Neither the dose nor the intestinal region influenced the bioavailability of fluvastatin significantly. The rate of absorption was, however, affected by both the dose and the site of administration; duodenum = jejunum > colon > ileum, and higher following the high dose. Increasing the i.v. dose from 2 to 20 micromol/kg decreased the clearance (26 +/- 3 to 12 +/- 1 mL/min/kg), the hepatic extraction (66 +/- 8 to 30 +/- 2%), and the volume of distribution (7.3 +/- 0.3 to 2.1 +/- 0.7 L/kg) for fluvastatin (p < 0.05). Neither bile cannulation nor bile sampling affected the pharmacokinetics. Fluvastatin was secreted into the bile, probably by active transport. The in vitro permeability for fluvastatin was high (>10 x 10(-6) cm/s). Indomethacin, but not the other inhibitors, affected the transport in both directions suggesting mrp2 to be involved. In silico, 93% of the dose was absorbed from

  18. 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

  19. Interaction of the main components from the traditional Chinese drug pair Chaihu-Shaoyao based on rat intestinal absorption.

    PubMed

    Chen, Yan; Wang, Jinyan; Yuan, Ling; Zhou, Lei; Jia, Xiaobin; Tan, Xiaobin

    2011-01-01

    The Chaihu-Shaoyao drug pair (Bupleuri Radix and Paeoniae Radix Alba) which is a traditional Chinese drug pair, has been widely used for anti-inflammatory purposes. Saikosaponin a (SSA), saikosaponin d (SSD) and paeoniflorin are identified as the main components in the pair. The present study focused on the interaction of the main components based on investigating their intestinal absorption using a four-site perfused rat intestinal model in order to clarify the mechanism of the compatibility of Chaihu-Shaoyao. The concentrations of SSA, SSD and paeoniflorin in the intestinal perfusate were determined by LC/MS or UPLC (Ultra Performance Liquid Chromatography) methods, followed by P*(eff) (effective permeability) and 10% ABS (the percent absorption of 10 cm of intestine) calculations. The results showed that all of the three main components displayed very low permeabilities (P*(eff) < 0.4), which implied their poor absorption in the rat intestine. The absorption levels of SSA and SSD were similar in intestine and higher in ileum than those in other intestinal regions in the decreasing order: colon, jejunum and duodenum. However, there is no significant difference in the absorption of paeoniflorin in the four segments (P < 0.05). The P*(eff) values of paeoniflorin exhibited an almost 2.11-fold or 1.90-fold increase in ileum when it was co-administrated with SSA and SSD, as well as 2.42-, 2.18-fold increase in colon, respectively, whereas the absorptions of SSA and SSD were not influenced by paeoniflorin. In conclusion, SSA and SSD could promote the absorption of paeoniflorin. To some extent this might explain the nature of the compatibility mechanisms of composite formulae in TCMs. PMID:22095024

  20. [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

  1. 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. PMID:26755265

  2. 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

  3. 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. PMID:26216471

  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. PMID:10902536

  5. 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.

  6. 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

  7. Hypouricemic effects of novel concentrative nucleoside transporter 2 inhibitors through suppressing intestinal absorption of purine nucleosides.

    PubMed

    Hiratochi, Masahiro; Tatani, Kazuya; Shimizu, Kazuo; Kuramochi, Yu; Kikuchi, Norihiko; Kamada, Noboru; Itoh, Fumiaki; Isaji, Masayuki

    2012-09-01

    We have developed concentrative nucleoside transporter 2 (CNT2) inhibitors as a novel pharmacological approach for improving hyperuricemia by inhibiting intestinal absorption of purines. Dietary purine nucleosides are absorbed in the small intestines by CNTs expressed in the apical membrane. In humans, the absorbed purine nucleosides are rapidly degraded to their final end product, uric acid, by xanthine oxidase. Based on the expression profile of human CNTs in digestive tract tissues, we established a working hypothesis that mainly CNT2 contributes to the intestinal absorption of purine nucleosides. In order to confirm this possibility, we developed CNT2 inhibitors and found that (2R,3R,4S,5R)-2-(6-amino-8-{[3'-(3-aminopropoxy)-biphenyl-4-ylmethyl]-amino}-9H-purin-9-yl)-5-hydroxymethyl-tetrahydrofuran-3,4-diol (KGO-2142) and 1-[3-(5-{[1-((2R,3R,4S,5R)-3,4-dihydroxy-5-hydroxymethyl-tetrahydrofuran-2-yl)-1H-benzimidazol-2-ylamino]-methyl}-2-ethoxyphenoxy)-propyl]-piperidine-4-carboxylic acid amide (KGO-2173) were inhibitory. These CNT2 inhibitors had potent inhibitory activity against inosine uptake via human CNT2, but they did not potently interfere with nucleoside uptake via human CNT1, CNT3 or equilibrative nucleoside transporters (ENTs) in vitro. After oral administration of KGO-2173 along with [(14)C]-inosine, KGO-2173 significantly decreased the urinary excretion of radioactivity at 6 and 24h in rats. Since dietary purine nucleosides are not utilized in the body and are excreted into the urine rapidly, this decrease in radioactivity in the urine represented the inhibitory activity of KGO-2173 toward the absorption of [(14)C]-inosine in the small intestines. KGO-2142 almost completely inhibited dietary RNA-induced hyperuricemia and the increase in urinary excretion of uric acid in cebus monkeys. These novel CNT2 inhibitors, KGO-2142 and KGO-2173, could be useful therapeutic options for the treatment of hyperuricemia. PMID:22709993

  8. Intestinal absorption of calcium from yogurt in lactase-deficient subjects.

    PubMed

    Wynckel, A; Jaisser, F; Wong, T; Drüeke, T; Chanard, J

    1991-01-01

    Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency. PMID:1747199

  9. Absorption of 3(2H)-furanones by human intestinal epithelial Caco-2 cells.

    PubMed

    Stadler, Nicole Christina; Somoza, Veronika; Schwab, Wilfried

    2009-05-13

    A number of 3(2H)-furanones are synthesized by fruits and have been found in cooked foodstuffs, where they impart flavor and odor because of their low perception thresholds. They show genotoxic properties in model studies but are also ranked among the antioxidants and anticarcinogens. This study examined the efficiency of intestinal absorption and metabolic conversion of 3(2H)-furanones by using Caco-2 cell monolayers as an intestinal epithelial cell model. The permeability of each agent was measured in both the apical to basal and basal to apical directions. 2,5-Dimethyl-4-methoxy-3(2H)-furanone (DMMF) showed the highest absorption rate in all experiments, while similar amounts of 4-hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF), 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF), and 4-hydroxy-5-methyl-3(2H)-furanone (HMF) were taken up. HDMF-glucoside was almost not absorbed but was hydrolyzed to a small extent. The transport of 3(2H)-furanones could not be saturated even at levels of 500 microM and occurred in both directions. Because the uptake was only slightly reduced by apical hyperosmolarity, passive diffusion by paracellular transport is proposed. PMID:19338346

  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. PMID:24776745

  11. Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids.

    PubMed

    Harrison, Earl H

    2012-01-01

    Vitamin A is an essential nutrient for humans and is converted to the visual chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in animal-derived foods is found as long chain acyl esters of retinol and these are digested to free fatty acids and retinol before uptake by the intestinal mucosal cell. The retinol is then reesterified to retinyl esters for incorporation into chlylomicrons and absorbed via the lymphatics or effluxed into the portal circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids such as β-carotene are found in plant-derived foods. These and other carotenoids are transported into the mucosal cell by scavenger receptor class B type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by oxygenase and reductase enzymes and the retinol so produced is available for absorption via the two pathways described above. The efficiency of vitamin A and carotenoid intestinal absorption is determined by the regulation of a number of proteins involved in the process. Polymorphisms in genes for these proteins lead to individual variability in the metabolism and transport of vitamin A and carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism. PMID:21718801

  12. Estimation of the Intestinal Absorption and Metabolism Behaviors of 2- and 3-Monochloropropanediol Esters.

    PubMed

    Kaze, Naoki; Watanabe, Yomi; Sato, Hirofumi; Murota, Kaeko; Kotaniguchi, Miyako; Yamamoto, Hiroshi; Inui, Hiroshi; Kitamura, Shinichi

    2016-08-01

    The regioisomers of the di- and mono-oleate of monochloropropanediol (MCPD) have been synthesized and subsequently hydrolyzed with pancreatic lipase and pancreatin to estimate the intestinal digestion and absorption of these compounds after their intake. The hydrolysates were analyzed by HPLC using a corona charged aerosol detection system, which allowed for the separation and detection of the different regioisomers of the MCPD esters. The hydrolysates were also analyzed by GC-MS to monitor the free MCPD. The results indicated that the two acyl groups of 2-MCPD-1,3-dioleate were smoothly hydrolyzed by pancreatic lipase and pancreatin to give free 2-MCPD. In contrast, the hydrolysis of 3-MCPD-1,2-dioleate proceeded predominantly at the primary position to produce 3-MCPD-2-oleate. 2-MCPD-1-oleate and 3-MCPD-1-oleate were further hydrolyzed to free 2- and 3-MCPD by pancreatic lipase and pancreatin, although the hydrolysis of 3-MCPD-2-oleate was 80 % slower than that of 3-MCPD-1-oleate. The intestinal absorption characteristics of these compounds were evaluated in vitro using a Caco-2 cell monolayer. The results revealed that the MCPD monooleates, but not the MCPD dioleates, were hydrolyzed to produce the free MCPD in the presence of the Caco-2 cells. The resulting free MCPD permeated the Caco-2 monolayer most likely via a diffusion mechanism because their permeation profiles were independent of the dose. Similar permeation profiles were obtained for 2- and 3-MCPDs. PMID:27023203

  13. Intestinal absorption of end products from digestion of carbohydrates and proteins in the pig.

    PubMed

    Rerat, A A

    1985-07-01

    The kinetics of appearance of various nutrients in the portal vein during the postprandial period was studied in conscious pigs by means of a technique based on measurement of the porto-arterial differences in nutrient concentrations simultaneously with that of the portal blood flow rate. The rate and level of appearance of sugars in the portal vein varied with the carbohydrate ingested. It was very rapid after intake of glucose and sucrose, slower after that of maize starch and very slow after that of lactose. The absorption of the latter became very rapid again if it was hydrolysed prior to its ingestion. During absorption, some sugars (fructose or galactose) released from the corresponding sucrose and lactose, respectively during digestion, were partly metabolized into glucose by the enterocyte. The rate of absorption of amino acids released in the digestive tract varied according to the origin of the food ingested, i.e. it was more rapid after intake of wheat or fish proteins than after that of barley. In the case of barley the absorption rate of amino acids differed from that of glucose of the starch. The profile of the amino acid mixtures appearing in the portal vein during absorption differed a little from the profiles of those present in the ingested proteins in the case of essential amino acids and differed much in the case of non essential amino acids. Some essential amino acids (histidine, aromatic amino acids) appeared more rapidly and others more slowly, (lysine, sulphur amino acids, arginine). Because of transaminations, only small amounts of glutamic acid occurred in the portal vein whereas the amounts of alanine as compared to those ingested, were very large. The hierarchy of amino acid absorption was the same whatever the protein studied (fish, wheat, barley). The appearance in the portal vein of alpha-amino nitrogen from enzyme hydrolysates perfused through the duodenum was more rapid than after perfusion of a mixture of free amino acids. During

  14. 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. PMID:20734997

  15. alpha-Ketoglutarate (AKG) absorption from pig intestine and plasma pharmacokinetics.

    PubMed

    Dabek, M; Kruszewska, D; Filip, R; Hotowy, A; Pierzynowski, L; Wojtasz-Pajak, A; Szymanczyk, S; Valverde Piedra, J L; Werpachowska, E; Pierzynowski, S G

    2005-12-01

    To study the absorption, metabolism and kinetics, the AKG (in different concentrations) was administered intravenously, intra-portally, orally and directly into the ileum or duodenum of pigs, chronically fitted with portal and jugular catheters and T-shaped cannula at the duodenum and ileum. Additionally, this study was conducted to determine the influence of low pH, Fe(2+) or/and SO on AKG gut absorption and conversely FeSO(4) and FeSO(4)/AKG on Fe(2+) gut absorption. It is concluded that AKG was significantly better absorbed from the upper small intestine than from the distal sections. Furthermore, low pH, Fe(2+) and/or SO ions enhanced AKG absorption. The AKG administered to the portal vein was rapidly eliminated from the blood (half-life less than 5 min). The short lifetime for AKG is probably dependent on quick metabolism in the enteorcyetes and liver. However, the prolonged half-life can be related to its low AKG blood concentration. The Fe(2+) concentrations in blood increased after FeSO(4) and FeSO(4)/AKG duodenal infusion. The implication of above observations is important for practical application of the AKG in animal and human nutrition as well in medicine. PMID:16401194

  16. Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes

    PubMed Central

    Duan, Franklin F.; Liu, Joy H.

    2015-01-01

    The inactive full-length form of GLP-1(1-37) stimulates conversion of both rat and human intestinal epithelial cells into insulin-secreting cells. We investigated whether oral administration of human commensal bacteria engineered to secrete GLP-1(1-37) could ameliorate hyperglycemia in a rat model of diabetes by reprogramming intestinal cells into glucose-responsive insulin-secreting cells. Diabetic rats were fed daily with human lactobacilli engineered to secrete GLP-1(1-37). Diabetic rats fed GLP-1–secreting bacteria showed significant increases in insulin levels and, additionally, were significantly more glucose tolerant than those fed the parent bacterial strain. These rats developed insulin-producing cells within the upper intestine in numbers sufficient to replace ∼25–33% of the insulin capacity of nondiabetic healthy rats. Intestinal tissues in rats with reprogrammed cells expressed MafA, PDX-1, and FoxA2. HNF-6 expression was observed only in crypt epithelia expressing insulin and not in epithelia located higher on the villous axis. Staining for other cell markers in rats treated with GLP-1(1-37)–secreting bacteria suggested that normal function was not inhibited by the close physical proximity of reprogrammed cells. These results provide evidence of the potential for a safe and effective nonabsorbed oral treatment for diabetes and support the concept of engineered commensal bacterial signaling to mediate enteric cell function in vivo. PMID:25626737

  17. Engineered commensal bacteria reprogram intestinal cells into glucose-responsive insulin-secreting cells for the treatment of diabetes.

    PubMed

    Duan, Franklin F; Liu, Joy H; March, John C

    2015-05-01

    The inactive full-length form of GLP-1(1-37) stimulates conversion of both rat and human intestinal epithelial cells into insulin-secreting cells. We investigated whether oral administration of human commensal bacteria engineered to secrete GLP-1(1-37) could ameliorate hyperglycemia in a rat model of diabetes by reprogramming intestinal cells into glucose-responsive insulin-secreting cells. Diabetic rats were fed daily with human lactobacilli engineered to secrete GLP-1(1-37). Diabetic rats fed GLP-1-secreting bacteria showed significant increases in insulin levels and, additionally, were significantly more glucose tolerant than those fed the parent bacterial strain. These rats developed insulin-producing cells within the upper intestine in numbers sufficient to replace ∼25-33% of the insulin capacity of nondiabetic healthy rats. Intestinal tissues in rats with reprogrammed cells expressed MafA, PDX-1, and FoxA2. HNF-6 expression was observed only in crypt epithelia expressing insulin and not in epithelia located higher on the villous axis. Staining for other cell markers in rats treated with GLP-1(1-37)-secreting bacteria suggested that normal function was not inhibited by the close physical proximity of reprogrammed cells. These results provide evidence of the potential for a safe and effective nonabsorbed oral treatment for diabetes and support the concept of engineered commensal bacterial signaling to mediate enteric cell function in vivo. PMID:25626737

  18. 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. PMID:25865420

  19. Sex and Food Influence on Intestinal Absorption of Ketoprofen Gastroresistant Formulation.

    PubMed

    Magallanes, Laura; Lorier, Marianela; Ibarra, Manuel; Guevara, Natalia; Vázquez, Marta; Fagiolino, Pietro

    2016-05-01

    Sixteen healthy volunteers (8 women and 8 men) participated in a 2-period, 2-treatment crossover study. A delayed-release gastroresistant formulation of ketoprofen was administered under fasting and fed conditions. Cmax , AUC, Cmax /AUC, and kel obtained after food coadministration did not differ from those calculated under fasting administration. Ninety-five percent confidence intervals for fed/fasting geometric mean ratio of Cmax /AUC and AUC were 0.80-1.14 and 0.80-1.23, respectively. A significant difference (P < .01) was found between lag-time medians (T0 ), with a longer T0 after food intake (5.5 vs 2.5 hours). Also, a significant difference between the medians of Tmax was found (P < .01), being 7.0 hours after food coadministration and 4.0 hours under fasting administration, but this difference disappeared once T0 was subtracted from Tmax . Cmax /AUC, which is related to drug absorption rate, showed significant differences between sexes. Men showed higher (P =.006) Cmax /AUC means (0.468 ± 0.094 vs 0.361 ± 0.087 h(-1) . Tmax was also significantly different (P < .05), being 4.0 (3.0-5.0) hours for men and 8.0 (5.0-10.0) hours for women. In conclusion, men showed a faster intestinal absorption rate with earlier time-to-peak plasma concentration of ketoprofen. Food coadministration extended the gastric residence time of formulation but exerted no effect on its intestinal absorption pattern. PMID:27163498

  20. 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

  1. Evaluation of intestinal absorption and mucosal toxicity using two promoters. II. Rat instillation and perfusion studies.

    PubMed

    Maher, Sam; Wang, Xuexuan; Bzik, Victoria; McClean, Siobhan; Brayden, David J

    2009-11-01

    We compared the effectiveness of two absorption promoters, sodium caprate (C(10)) and melittin, in increasing the bioavailability (F) of poorly absorbed paracellular flux markers across the intestinal mucosae of rats in situ, together with examination of their effects on morphology. C(10) (100 mM) and melittin (50 microM) significantly increased absorption of FITC-dextran-4 kDa (FD4) following jejunal and colonic instillations. F of FD4 following jejunal instillations with C(10) was increased from 0.07% to 2.3%, while it was increased from 0.07% to 0.53% in the presence of melittin. F of FD4 following colonic instillations with C(10) was increased from 1% to 33% while melittin increased it from 1% to 7%. F of FD70 was unchanged in colonic instillations in the presence of either of the two agents, indicating size limitations of the permeability enhancement effects. In rat jejunal perfusions, C(10) (50 mM) and melittin (50 microM) significantly increased [(14)C]-mannitol permeability by 9- and 1.9-fold respectively. C(10) was more effective than melittin in increasing fluxes in all models. Histology of intestinal sections exposed to either promoter showed mild mucosal damage at those concentrations effective at promoting absorption. Electron microscopy revealed epithelial cell damage induced by both enhancers accompanied by truncation of microvilli, and sloughing. Overall, both melittin and C(10) improved bioavailability of polar sugars across the jejunum and colon of rats in situ, which was associated with some degree of mucosal damage. PMID:19664704

  2. 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.

  3. 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

  4. The effect of cytokines on intestinal sugar absorption during sepsis in rabbits.

    PubMed

    Garcia-Barrios, A; Gascon, S; Rodriguez-Yoldi, M J

    2013-10-01

    The endotoxin that triggers an immune response to Gram-negative bacterial infection namely lipopolysaccharide (LPS), is also associated with gastrointestinal abnormalities and induces the release of proinflammatory cytokines such as IL-1 and TNF-α. The main aim of this study was to determine the effect of cytokine release on intestinal D-fructose absorption in LPS-treated rabbits in order to provide information that could be used to understand their septic status. The results obtained, using whole tissue and brush border membrane vesicles from rabbit jejunum, showed that LPS, TNF-α and IL-1β inhibit d-fructose absorption across the jejunum. The effect of LPS is completely reversed by a TNF-α antagonist and partially by a specific IL-1 receptor antagonist (IL-1ra) and disappears completely in the presence of both these cytokine antagonists. Similarly, the effects of TNF-α and LPS were not totally blocked by IL-1ra, whereas the effect of IL-1β disappeared completely in the presence of a TNF antagonist. In summary, these results show that TNF-α and IL-1β could act synergistically on sugar absorption in rabbit with LPS-induced sepsis. In addition, the effects of IL-1β depend on, or are related to TNF-α production since this effect returns to basal (control) levels in the presence of a TNF-α antagonist. PMID:23850132

  5. Emulsion-based colloidal nanosystems for oral delivery of doxorubicin: improved intestinal paracellular absorption and alleviated cardiotoxicity.

    PubMed

    Kim, Ji-Eon; Yoon, In-Soo; Cho, Hyun-Jong; Kim, Dong-Hwan; Choi, Young-Hee; Kim, Dae-Duk

    2014-04-10

    We have previously reported that the limited intestinal absorption via the paracellular pathway may be the primary cause of the low oral bioavailability of doxorubicin (DOX). In this study, we have formulated medium chain glycerides-based colloidal nanosystems to enhance the intestinal paracellular absorption of DOX and reduce its cardiotoxicity. The DOX formulations prepared by the construction of pseudo-ternary phase diagram were characterized in terms of their droplet size distribution, viscosity, drug loading, and drug release. Further evaluation was conducted by an in vitro Caco-2 transport study as well as in situ/in vivo intestinal absorption, bioavailability and toxicity studies. Compared with DOX solution, these formulations enhanced the absorptive transport of DOX across Caco-2 cell monolayers at least partly due to the paracellular-enhancing effects of their lipidic components. Moreover, the in situ intestinal absorption and in vivo oral bioavailability of DOX in rats were markedly enhanced. In addition, no discernible damage was observed in the rat jejunum after oral administration of these DOX formulations while the cardiac toxicity was significantly reduced when compared with intravenous DOX solution. Taken together, the medium chain glycerides-based colloidal nanosystems prepared in this study represent a potentially effective oral delivery system for DOX. PMID:24463005

  6. 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

  7. Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5.

    PubMed

    Arakawa, Hiroshi; Shirasaka, Yoshiyuki; Haga, Makoto; Nakanishi, Takeo; Tamai, Ikumi

    2012-09-01

    Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. PMID:22899169

  8. Augmented cholesterol absorption and sarcolemmal sterol enrichment slow small intestinal transit in mice, contributing to cholesterol cholelithogenesis

    PubMed Central

    Xie, Meimin; Kotecha, Vijay R; Andrade, Jon David P; Fox, James G; Carey, Martin C

    2012-01-01

    Cholesterol gallstones are associated with slow intestinal transit in humans as well as in animal models, but the molecular mechanism is unknown. We investigated in C57L/J mice whether the components of a lithogenic diet (LD; 1.0% cholesterol, 0.5% cholic acid and 17% triglycerides), as well as distal intestinal infection with Helicobacter hepaticus, influence small intestinal transit time. By quantifying the distribution of 3H-sitostanol along the length of the small intestine following intraduodenal instillation, we observed that, in both sexes, the geometric centre (dimensionless) was retarded significantly (P < 0.05) by LD but not slowed further by helicobacter infection (males, 9.4 ± 0.5 (uninfected), 9.6 ± 0.5 (infected) on LD compared with 12.5 ± 0.4 and 11.4 ± 0.5 on chow). The effect of the LD was reproduced only by the binary combination of cholesterol and cholic acid. We inferred that the LD-induced cholesterol enrichment of the sarcolemmae of intestinal smooth muscle cells produced hypomotility from signal-transduction decoupling of cholecystokinin (CCK), a physiological agonist for small intestinal propulsion in mice. Treatment with ezetimibe in an amount sufficient to block intestinal cholesterol absorption caused small intestinal transit time to return to normal. In most cholesterol gallstone-prone humans, lithogenic bile carries large quantities of hepatic cholesterol into the upper small intestine continuously, thereby reproducing this dietary effect in mice. Intestinal hypomotility promotes cholelithogenesis by augmenting formation of deoxycholate, a pro-lithogenic secondary bile salt, and increasing the fraction of intestinal cholesterol absorbed. PMID:22331417

  9. Augmented cholesterol absorption and sarcolemmal sterol enrichment slow small intestinal transit in mice, contributing to cholesterol cholelithogenesis.

    PubMed

    Xie, Meimin; Kotecha, Vijay R; Andrade, Jon David P; Fox, James G; Carey, Martin C

    2012-04-15

    Cholesterol gallstones are associated with slow intestinal transit in humans as well as in animal models, but the molecular mechanism is unknown. We investigated in C57L/J mice whether the components of a lithogenic diet (LD; 1.0% cholesterol, 0.5% cholic acid and 17% triglycerides), as well as distal intestinal infection with Helicobacter hepaticus, influence small intestinal transit time. By quantifying the distribution of 3H-sitostanol along the length of the small intestine following intraduodenal instillation,we observed that, in both sexes, the geometric centre (dimensionless) was retarded significantly (P <0.05) by LD but not slowed further by helicobacter infection (males, 9.4±0.5 (uninfected), 9.6±0.5 (infected) on LD compared with 12.5±0.4 and 11.4±0.5 on chow). The effect of the LD was reproduced only by the binary combination of cholesterol and cholic acid. We inferred that the LD-induced cholesterol enrichment of the sarcolemmae of intestinal smooth muscle cells produced hypomotility from signal-transduction decoupling of cholecystokinin (CCK), a physiological agonist for small intestinal propulsion in mice. Treatment with ezetimibe in an amount sufficient to block intestinal cholesterol absorption caused small intestinal transit time to return to normal. In most cholesterol gallstone-prone humans, lithogenic bile carries large quantities of hepatic cholesterol into the upper small intestine continuously, thereby reproducing this dietary effect in mice. Intestinal hypomotility promotes cholelithogenesis by augmenting formation of deoxycholate, a pro-lithogenic secondary bile salt, and increasing the fraction of intestinal cholesterol absorbed. PMID:22331417

  10. Sucrase-isomaltase damps rate of mealtime small intestinal mucosal starch oligomer digestion to glucose while maltase-glucoamylase amplifies during snacking

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Food starches contribute about half of the energy content of the human diet. Starches are first hydrolyzed by amylases to soluble glucose oligomers which are hydrolyzed to free glucose by small intestinal sucrase-isomaltase (SI) and maltose-glucoamylase (MGAM). Pooled human duodenal biopsies were as...