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Sample records for intestinal glucose absorption

  1. 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

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

    SciTech Connect

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

    2011-01-07

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

  3. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    PubMed

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC50 = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU50 = 2.68 ± 0.75 %) or without (GU50 = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  4. Accelerated intestinal glucose absorption in morbidly obese humans: relationship to glucose transporters, incretin hormones, and glycemia.

    PubMed

    Nguyen, Nam Q; Debreceni, Tamara L; Bambrick, Jenna E; Chia, Bridgette; Wishart, Judith; Deane, Adam M; Rayner, Chris K; Horowitz, Michael; Young, Richard L

    2015-03-01

    Intestinal glucose absorption is mediated by sodium-dependent glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses. This study aimed to examine intestinal glucose absorption in morbidly obese humans and its relationship to the expression of STR and glucose transporters, glycemia, and incretin responses. Seventeen nondiabetic, morbidly obese subjects (body mass index [BMI], 48 ± 4 kg/m(2)) and 11 lean controls (BMI, 25 ± 1 kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-minute intraduodenal glucose infusion (30 g glucose and 3 g 3-O-methylglucose [3-OMG]). Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), insulin, and glucagon were measured over 270 minutes. Expression of duodenal SGLT-1, GLUT2, and STR (T1R2) was quantified by PCR. The increase in plasma 3-OMG (P < .001) and blood glucose (P < .0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r = 0.78, P < .01). In response to intraduodenal glucose, plasma GIP (P < .001), glucagon (P < .001), and insulin (P < .001) were higher, but GLP-1 (P < .001) was less in the obese compared with lean. Expression of SGLT-1 (P = .035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r = 0.60, P = .01), GIP (r = 0.67, P = .003), and insulin (r = 0.58, P = .02). In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes.

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

    PubMed

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

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

  6. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    PubMed Central

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONS Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  7. Nonruminant Nutrition Symposium: intestinal glucose sensing and regulation of glucose absorption: implications for swine nutrition.

    PubMed

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

    2011-06-01

    The Na(+/)glucose cotransporter (SGLT1) is the major route for the transport of dietary sugars from the lumen of the intestine into enterocytes. Regulation of this protein is essential for the provision of glucose to the body and avoidance of intestinal malabsorption. This has important nutritional implications in particular for young and growing animals. It has been demonstrated that dietary sugars and artificial sweeteners increase SGLT1 expression and the capacity of the gut to absorb monosaccharides. Furthermore, diets supplemented with artificial sweeteners have been shown to improve growth and performance of weaning piglets. In this review, after describing the organization of intestinal epithelium, the type of gut hormones released in response to dietary carbohydrates, the mechanism underlying the transcellular transport of glucose in the intestine is outlined. Next, a historical background to the work carried out in various laboratories aimed at identifying molecular mechanisms involved in regulation of intestinal glucose transporter, SGLT1, is described. Subsequently, the more recent data on the role of intestinal glucose, or sweet, sensor T1R2 + T1R3, a G protein-coupled receptor, required for upregulation of SGLT1 by dietary sugars and artificial sweeteners, are presented. The glucose sensor subunits, T1R2 + T1R3, are members of the taste receptor family 1, T1R, and are expressed in the gut enteroendocrine cells. Sensing of dietary sugars and artificial sweeteners by T1R2 + T1R3 activates a pathway in endocrine cells leading to secretion of gut hormones. Finally, after describing molecular mechanisms by which a specific gut hormone released by endocrine cells may regulate SGLT1 expression in the neighboring absorptive enterocytes, the application of these findings to enhancing intestinal capacity to absorb dietary sugars in weaning piglets is presented. A better understanding of the molecular events involved in regulation of SGLT1 will allow the

  8. The effects of critical illness on intestinal glucose sensing, transporters, and absorption.

    PubMed

    Deane, Adam M; Rayner, Chris K; Keeshan, Alex; Cvijanovic, Nada; Marino, Zelia; Nguyen, Nam Q; Chia, Bridgette; Summers, Matthew J; Sim, Jennifer A; van Beek, Theresia; Chapman, Marianne J; Horowitz, Michael; Young, Richard L

    2014-01-01

    Providing effective enteral nutrition is important during critical illness. In health, glucose is absorbed from the small intestine via sodium-dependent glucose transporter-1 and glucose transporter-2, which may both be regulated by intestinal sweet taste receptors. We evaluated the effect of critical illness on glucose absorption and expression of intestinal sodium-dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors in humans and mice. Prospective observational study in humans and mice. ICU and university-affiliated research laboratory. Human subjects were 12 critically ill patients and 12 healthy controls. In the laboratory 16-week-old mice were studied. Human subjects underwent endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was biopsied before and after infusion. Mice were randomized to cecal ligation and puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8). At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused intraduodenally prior to mucosal tissue collection. Quantitative polymerase chain reaction was performed to measure absolute (human) and relative levels of sodium-dependent glucose transporter-1, glucose transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood samples were assayed for 3-O-methylglucose to estimate glucose absorption. Glucose absorption was three-fold lower in critically ill humans than in controls (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced 49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose transporter-2, and T1R2

  9. Glucose and amino acid absorption in house sparrow intestine and its dietary modulation.

    PubMed

    Caviedes-Vidal, E; Karasov, W H

    1996-09-01

    We acclimated house sparrows (Passer domesticus; 26 g) to high-starch (HS), high-protein (HP), and high-lipid (HL) diets and tested the predictions that uptake of D-glucose and amino acids will be increased with increased levels of dietary carbohydrate and protein, respectively. HS birds had lower mediated D-glucose uptake rate than HP birds. Total uptake of L-leucine at low concentration (0.01 mM), but not of L-proline at 50mM, was increased by dietary protein. Measures of D-glucose maximal mediated uptake (1.2 +/- 0.2 nmol.min-1.mg-1) and intestinal mass (1 g) indicated that the intestine's mediated uptake capacity was only approximately 10% of the D-glucose absorbed at the whole animal level. This implied that nonmediated glucose absorption predominated. We applied a pharmacokinetic technique to measure in vivo absorption of L-glucose, the stereoisomer that does not interact with the Na(+)-glucose cotransporter. At least 75% of L-glucose that was ingested was apparently absorbed. This adds to the increasing evidence that substantial passive glucose absorption occurs in birds and may explain why mediated D-glucose uptake does not increase on high-carbohydrate diets.

  10. Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.

    PubMed

    Ma, Jing; Chang, Jessica; Checklin, Helen L; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

    2010-09-01

    It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0.9% saline) or control (0.9% saline) at 4 ml/min for 150 min (T = - 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2.5 %), were co-infused intraduodenally (T = 0-120 min; 4.2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P < 0.005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.

  11. Intestinal glucose absorption in calves as affected by different carbohydrate sources.

    PubMed

    Klinger, S; Noci, B; Müller, K; Breves, G

    2013-04-01

    From numerous recent studies, it has been demonstrated that the development of the forestomach system in ruminants and thus microbial carbohydrate fermentation do not exclude the potential of the small intestines for enzymatic carbohydrate digestion and subsequent monosaccharide absorption. However, the role of regulatory nutritional factors is still under discussion. Therefore, we investigated the kinetic parameters of intestinal Na(+) -dependent glucose absorption and SGLT1 expression using isolated brush border membrane vesicles (BBMV) from the jejunum of 10-week-old calves kept on either hay, concentrate or corn silage-based diets in addition to milk replacer. While the maximal transport capacity was significantly higher for concentrate and corn silage-fed animals, SGLT1 protein expression was highest in BBMV isolated from hay-fed animals. This observation differs from the prevalent conception that induction of Na(+) -dependent glucose uptake via SGLT1 is based on an increased number of transporters at the brush border membrane.

  12. Disordered control of intestinal sweet taste receptor expression and glucose absorption in type 2 diabetes.

    PubMed

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

    2013-10-01

    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 × 10(4) and +5.8 × 10(4) copies, respectively) but decreased in healthy subjects during hyperglycemia (-1.4 × 10(4) copies). T1R2 levels increased significantly in type 2 diabetic patients under the same conditions (+6.9 × 10(5) 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.

  13. 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

  14. Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

    PubMed

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2017-02-01

    This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

  15. Soybean impairs Na(+)-dependent glucose absorption and Cl- secretion in porcine small intestine.

    PubMed

    Boudry, Gaëlle; Lallès, Jean-Paul; Malbert, Charles Henri; Grøndahl, Marie Louise; Unmack, Martin Andreas; Skadhauge, Erik

    2003-01-01

    Recent evidence indicates that soybean, which is widely used in animal nutrition, could directly alter intestinal ion and nutrient transport. However, the mechanisms involved are still unknown. The aim of the study was to investigate the effect of three differently treated soybean products on the glucose and Cl- transport capacity in porcine small intestine by the Ussing chamber technique. Jejunal and ileal piglet epithelial tissues were pre-incubated with extracts of raw soybean flour (RSF), heated soybean flour (HSF), or ethanol heat-treated soybean protein concentrate (SPC). The Na(+)-dependent glucose co-absorption capacity was then measured as an increase in the short-circuit current (ISC) after luminal addition of D-glucose. The effect of the soybean products on cAMP-dependent Cl- secretion was measured as the increase in ISC after the addition of the phosphodiesterase inhibitor, theophylline, while nervous regulation of Cl- secretion was investigated by the addition of the enteric neurotransmitters; 5-hydroxytryptamine (5-HT), substance P and vasoactive intestinal polypeptide (VIP). Incubation with RSF and HSF induced a 30% decrease of the Na(+)-dependent glucose absorption capacity in the jejunum. The effect was similar for RSF in the ileum. Theophylline-induced secretion was decreased by 30% after incubation with RSF, HSF and SPC but only in the jejunum. 5-HT-, substance P- and VIP-induced secretion were not altered by incubation with soybean extracts except in the HSF-incubated where the substance P-induced secretion was significantly reduced. In conclusion, soybean contains ethanol-sensitive heat-insensitive compounds impairing Na(+)-dependent glucose absorption in the jejunum and ileum, and ethanol- and heat-insensitive compounds causing an acute impairment of cAMP-dependent jejunal secretion.

  16. Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass.

    PubMed

    Nguyen, Nam Q; Debreceni, Tamara L; Bambrick, Jenna E; Bellon, Max; Wishart, Judith; Standfield, Scott; Rayner, Chris K; Horowitz, Michael

    2014-09-01

    To evaluate the effect of modulating pouch emptying (PE) and SI transit of glucose after Roux-en-Y gastric bypass (RYGB) on blood glucose, incretin hormones, glucose absorption and gastrointestinal (GI) symptoms. Ten RYGB patients were studied twice in random order, receiving either a 150 ml glucose drink (200 kcal) or the same solution infused into the proximal Roux-limb at 4 kcal/min. Data were compared with 10 healthy volunteers who received a 4 kcal/min duodenal infusion. PE, cecal arrival time (CAT), blood glucose, plasma 3-O-methylglucose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), and GI symptoms were measured. In RYGB subjects, the glucose drink emptied very rapidly (PE t50 = 3 ± 1 min) and intestinal glucose infusion was associated with higher blood glucose and plasma 3-OMG, but lower plasma GLP-1, GIP, insulin, and GI symptoms than oral glucose (all P < 0.001), and comparable to volunteers. In RYGB subjects, CAT correlated inversely with peak GLP-1 (r = -0.73, P = 0.01), and plasma 3-OMG correlated tightly blood glucose (r = 0.94, P < 0.0001). After RYGB, reducing intestinal glucose delivery to 4 kcal/min is associated with higher blood glucose, greater glucose absorption, lower incretin responses, and less GI symptoms, supporting rapid transit contribution to the exaggerated incretin responses and "dumping symptoms". © 2014 The Obesity Society.

  17. Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

    PubMed

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2017-04-01

    Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50 = 3.5% ± 1.6%) or without insulin (GU50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

  18. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2

    PubMed Central

    Mace, Oliver J; Affleck, Julie; Patel, Nick; Kellett, George L

    2007-01-01

    Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptors are coupled through G-proteins, α-gustducin and transducin, to activate phospholipase C β2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express α-gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanism analogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with α-gustducin, transducin or phospholipase C β2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+–glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium ∼ sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulation occurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and α-gustducin versus T1R1, transducin and phospholipase C β2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing and nutrition in the treatment of obesity and diabetes. PMID:17495045

  19. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study.

    PubMed

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R

    2013-08-01

    Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0-2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0-6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.

  20. 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. Copyright © 2014 American Dairy Science

  1. Role of glucose transporters in the intestinal absorption of gastrodin, a highly water-soluble drug with good oral bioavailability.

    PubMed

    Cai, Zheng; Huang, Juan; Luo, Hui; Lei, Xiaolu; Yang, Zhaoxiang; Mai, Yang; Liu, Zhongqiu

    2013-07-01

    Gastrodin, a sedative drug, is a highly water-soluble phenolic glucoside with poor liposolubility but exhibits good oral bioavailability. The current study aims to investigate whether glucose transporters (GLTs) are involved in the intestinal absorption of gastrodin. The intestinal absorption kinetics of gastrodin was determined using the rat everted gut sac model, the Caco-2 cell culture model and the perfused rat intestinal model. In vivo pharmacokinetic studies using diabetic rats with high GLT expression were performed. Saturable intestinal absorption of gastrodin was observed in rat everted gut sacs. The apparent permeability (Papp) of gastrodin from the apical (A) to basolateral (B) side in Caco-2 cells was two-fold higher than that from B to A. Glucose or phlorizin, a sodium-dependent GLT (SGLT) inhibitor, reduced the absorption rates of gastrodin from perfused rat intestines. In vivo pharmacokinetic studies showed that the time of maximum plasma gastrodin concentration (Tmax) was prolonged from 28 to 72 min when orally co-administered with four times higher dose of glucose. However, the Tmax of gastrodin in diabetic rats was significantly lowered to 20 min because of the high intestinal SGLT1 level. In conclusion, our findings indicate that SGLT1 can facilitate the intestinal absorption of gastrodin.

  2. Effect of giardiasis combined with low-protein diet on intestinal absorption of glucose and electrolytes in gerbils.

    PubMed

    Gomes, Maria Aparecida; de Oliveira, Dirce Ribeiro; de Freitas, Sabrina Emanuele; de Pinho Viana, Marcelo; Borges, Elizabeth Lage

    2012-08-01

    Studies have shown that symptomatic infection by Giardia lamblia causes acute or chronic diarrhea, dehydration, abdominal pain and malabsorption, leading to undernutrition and weight loss. The aim of the present study was to evaluate the effects of giardiasis and its combination with a low-protein diet on the intestinal absorption of glucose and electrolytes in gerbils. The intestinal absorption of glucose, sodium and potassium was investigated in male gerbils weighing 46-64 g (n≥5). A Tyrode solution containing twice the glucose, sodium and potassium concentration (pH 7.4) was infused through the intestinal loops for 40 min. Glucose absorption was not significantly affected by diet and infection. However, there was a significant increase in sodium absorption in the Giardia-infected group (57.2±6.1, p<0.05) in comparison to the control, low-protein diet and low-protein diet+Giardia-infected groups (8.9±6.5, 2.8±11.1 and 0.8±7.9, respectively; p<0.05). Moreover, potassium was absorbed in the Giardia-infected group (0.45±0.30), while the other groups exhibited potassium secretion. A low-protein diet and Giardia infection had no influence over glucose absorption. However, Giardia infection increased sodium and potassium uptake, suggesting a compensatory mechanism for maintaining homeostasis after likely hypernatremia and hypokalemia caused by the diarrhea that accompanies giardiasis.

  3. [The effect of glucose on antidiuretic hormone absorption in the rat and frog small intestine].

    PubMed

    Prutskova, N P; Tse, Gao; Shakhmatova, E I

    2005-03-01

    Administration of 5 ml/100 g body weight of 1% glucose solution to stomach produced the same diuretic kidney response in fasted Wistar rats as administration of the same amount of water. Intragastric administration of arginine vasopressin along with the water load evoked an antidiuretic response. Arginine vasopressin in the same volume of glucose induced no kidney response difference as compared with the hormone action in experiments with water load. 0.1 nmol of arginine vasotocin, having been itroduced into the rat isolated ileum, prevented the effect of glucose on the hormone absoption. 0.1 nmol of arginine vasotocin, having been introduced into the frog isolated ileum along with isotonic glucose solution, increased the hormone absorption; fructose did not affect this process whereas mannitol decreased absorption ofarginine vasotocin. This absorption was also reduced by intraileal introduction of arginine vasotocin with the hypotonic Ringer solution. The findings suggest that glucose in the rat gastrointestinal tract does not affect arginine vasopressin absorption in vivo, whereas in the frog ileum glucose increases arginine vasotocin absorption in vitro.

  4. Luminal Glucose Does Not Enhance Active Intestinal Calcium Absorption in mice: Evidence Against a Role for Cav1.3 as a Mediator of Calcium Uptake During Absorption

    PubMed Central

    Reyes-Fernandez, Perla C.; Fleet, James C.

    2015-01-01

    Intestinal Ca absorption occurs through a 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-regulated transcellular pathway, especially when habitual dietary Ca intake is low. Recently the L-type voltage-gated Ca channel, Cav1.3, was proposed to mediate active, transcellular Ca absorption in response to membrane depolarization caused by elevated luminal glucose levels following a meal. We tested the hypothesis that high luminal glucose could reveal a role for Cav1.3 in active intestinal Ca absorption in mice. Nine week-old male C57BL/6J mice were fed AIN93G diets containing either low (0.125%) or high (1%) Ca for 1 week and Ca absorption was examined by an oral gavage method using a 45Ca-transport buffer containing 25 mmol/L of glucose or fructose. Transient receptor potential vanilloid 6 (TRPV6), Calbindin D9k (CaBPD9k) and Cav1.3 mRNA levels were measured in the duodenum, jejunum and ileum. TRPV6 and CaBPD9k expression were highest in the duodenum, where active, 1,25(OH)2D3-regulated Ca absorption occurs while Cav1.3 mRNA levels were similar across the intestinal segments. As expected, the low Ca diet increased renal cytochrome p450-27B1 (CYP27B1) mRNA (p=0.003), serum 1,25(OH)2D3 (p<0.001) and Ca absorption efficiency by 2-fold with the fructose buffer. However, the glucose buffer used to favor Cav1.3 activation did not increase Ca absorption efficiency (p=0.6) regardless of the dietary Ca intake level. Collectively, our results show that glucose did not enhance Ca absorption and they do not support a critical role for Cav1.3 in either basal or vitamin D-regulated intestinal Ca absorption in vivo. PMID:26403486

  5. Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

    PubMed

    Chukwuma, Chika Ifeanyi; Mopuri, Ramgopal; Nagiah, Savania; Chuturgoon, Anil Amichund; Islam, Md Shahidul

    2017-08-02

    Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

  6. 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

  7. Ceratonia siliqua L. (immature carob bean) inhibits intestinal glucose absorption, improves glucose tolerance and protects against alloxan-induced diabetes in rat.

    PubMed

    Rtibi, Kaïs; Selmi, Slimen; Grami, Dhekra; Saidani, Khouloud; Sebai, Hichem; Amri, Mohamed; Eto, Bruno; Marzouki, Lamjed

    2017-06-01

    This study was designed to investigate the effects of immature carob pod aqueous extract (ICPAE) on intestinal glucose absorption in vitro and in vivo using an oral glucose tolerance test (OGTT) as well as the potential antidiabetic effect in alloxan-induced diabetic rats. OGTT was carried by administration of glucose (2 g kg(-1) , p.o.) and after treatment with extract (50, 100 and 200 mg kg(-1) body weight). Diabetes was induced by single intraperitoneal injection of alloxan (150 mg kg(-1) ). However, the extracts at various doses or glibenclamide (GLB, 10 mg kg(-1) body weight) were given by oral administration for 2 weeks. ICPAE (50-2000 µg mL(-1) ) exerted dose-dependent reduction of sodium-dependent glucose transport across isolated mice jejunum and the maximal inhibition exceeded 50%.The ICPAE treatment improved glucose tolerance. More importantly, ICPAE at various doses showed a significant reduction in blood glucose and biochemical profiles in diabetic rats. Our findings confirm that the degree of maturity of carob characterized by a different phytochemical composition may be responsible for these actions. Therefore, these compounds may be used as a food supplement in hyperglycemia and diabetes treatments. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. 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.

  9. Incomplete intestinal absorption of fructose.

    PubMed Central

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

    1984-01-01

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

  10. Neural regulation of intestinal nutrient absorption.

    PubMed

    Mourad, Fadi H; Saadé, Nayef E

    2011-10-01

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

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

    PubMed

    Reyes-Fernandez, Perla C; Fleet, James C

    2015-11-01

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

  12. Real-time monitoring of glucose and phenols intestinal absorption through an integrated Caco-2TC7cells/biosensors telemetric device: Hypoglycemic effect of fruit phytochemicals.

    PubMed

    Barberis, Antonio; Garbetta, Antonella; Cardinali, Angela; Bazzu, Gianfranco; D'Antuono, Isabella; Rocchitta, Gaia; Fadda, Angela; Linsalata, Vito; D'Hallewin, Guy; Serra, Pier Andrea; Minervini, Fiorenza

    2017-02-15

    An integrated device for real-time monitoring of glucose and phenols absorption, that consists of a sensors/biosensors system (SB) and a Caco-2TC7 human intestinal cell culture, is described in this study. The SB is composed of a glucose oxidase-based biosensor, a sentinel platinum sensor, a laccase/tyrosinase-based biosensor and a sentinel carbon sensor, all located in the basolateral compartment (BC) of a cell culture plate. Caco-2TC7 cells, differentiated on culture inserts, separated the apical compartment that simulates the intestinal lumen, from the BC which represented the bloodstream. The system recorded currents relative to glucose (1mM) absorption, obtaining bioavailability values (5.1%) comparable to HPLC analysis (4.8%). Phloridzin and phloretin, specific phenolic inhibitors of SGLT1 and GLUT2 glucose transporters, reduced the glucose transport of almost 10 times. They were minimally absorbed in the BC with a bioavailability of 0.13% and 0.49% respectively. The hypoglycemic potential of blueberry and pomegranate juices was also studied. In particular, the amount of glucose absorbed through the Caco-2TC7 monolayer was 8‰ for pomegranate and 1.7‰ for blueberry, demonstrating the potential hypoglycemic effect of the juices. Polyphenols absorption was also monitored by the SB and an increase was recorded during the first 50min in presence of both blueberry and pomegranate juices, then a constant decrease occurred. The proposed device has been developed as innovative tool for the dynamic monitoring of natural compounds effects on glucose absorption, in order to manage postprandial hyperglycemia. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat diet-induced lipotoxicity and oxidative stress.

    PubMed

    Jabri, Mohamed-Amine; Sakly, Mohsen; Marzouki, Lamjed; Sebai, Hichem

    2017-03-01

    The present study aimed to investigate the inhibitory effect of chamomile decoction extract (CDE) on intestinal glucose absorption as well as its protective role against high fat diet (HFD)-induced obesity and lipotoxicity in rats. We used the Ussing chamber system to investigate the effect of CDE on intestinal transport of glucose. Male Wistar rats were fed HFD for six weeks to provoke obesity. CDE (100mg/kg, b.w. p.o.) has been per orally administered to HFD fed rats. Ex vivo, we found that CDE significantly and dose-dependently increased intestinal absorption of glucose. In vivo, HFD increased the body, liver and kidney weights, while CDE treatment showed a significant protective effects. High fat diet induced also a lipid profiles disorder and a disturbances in kidney and liver function parameters. Moreover liver and kidney lipotoxicity is accompanied by an oxidative stress status characterized by increased lipoperoxidation, depletion of antioxidant enzymes activity and non-enzymatic antioxidant (-SH groups and GSH) levels as well as increased levels of free iron, hydrogen peroxide (H2O2) and calcium. However, treatment with CDE alleviated all the deleterious effects of HFD feed. These findings suggest that chamomile decoction extract can be used as functional beverage against obesity, hyperglycemia and hyperlipidemia.

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

    PubMed Central

    Booth, D A; Jarman, S P

    1976-01-01

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

  15. [Study on intestinal absorption rate of glucose electrolyte solution during enteral resuscitation of 35% total body surface area burn injury in dog].

    PubMed

    Che, Jin-wei; Hu, Sen; Du, Ying; Bao, Cheng-mei; Tian, Yi-jun; Wang, Lei; Sheng, Zhi-yong

    2008-03-01

    To investigate the intestinal absorption rate of glucose-electrolyte solution (GES) during enteral resuscitation of burn injury in Beagle dogs, and compare the effect of enteral intake with that of intravenous infusion resuscitation. Twelve male Beagle dogs were subjected to a 35% total body surface area (TBSA) full-thickness flame III degree injury. Thirty minutes after burn, each dog was given either enteral resuscitation with a GES (EGES group) or intravenous resuscitation with lactated Ringer's solution (IVLR group), and the amount and speed of replenishment of fluid were in accordance with Parkland formula. In the first 8 hours post burn, intestinal absorption rates of water and Na+ were continuously assessed using phenol red as a nonabsorbable marker for water absorption rate. The plasma volume (PV) was measured by the dye (indocyanine green) dilution technique, and the plasma concentration of Na+, mean arterial pressure (MAP) cardiac output (CO), and urine volume were also determined in the first 8 hours. All above measurement were performed in animals without anesthesia. At the end of 8-hour-period of experiment, the remnant fluids in the intestine were collected to calculate the total volume of fluid absorbed in 8 hours. The intestinal absorption rates of water and Na+ reduced markedly down to lowest level (21% and 37% of pre-injury level) at 3.5 hours post burn, and then increased slowly. But the mean absorption rate of water was similar to infusing rate according to Parkland formula [(99+/-47) mlxh(-1)xm(-1) vs. (81+/-11) mlxh(-1)xm(-1), P>0.05]. The total fluid absorbed by intestine was (94.8+/-3.7)% of the total fluid infused within 8 hours post burn. There were no significant differences in plasma concentration of Na+, MAP and CO between two groups at 8 hours post burn. The urine volume and PV at 4 hours in EGES group were lower than those in IVLR group (both P<0.05), but those indexes at 8 hours showed no significant difference between two groups

  16. Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis

    PubMed Central

    Massart, J; Robin, MA; Noury, F; Fautrel, A; Lettéron, P; Bado, A; Eliat, PA; Fromenty, B

    2012-01-01

    BACKGROUND AND PURPOSE Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy. Metabolic and hepatic effects of pentoxifylline were assessed in a murine model of obesity and type 2 diabetes. EXPERIMENTAL APPROACH Pentoxifylline (100 mg·kg−1·day−1) was administered for 4 days or 3 weeks in lean and obese/diabetic ob/ob mice. Plasma lipids, glucose, other metabolites and relevant enzymes were measured by standard assays. Hepatic lipids in vivo were assessed with magnetic resonance spectroscopy and by histology. Hepatic extracts were also analysed with RT-PCR and Western blotting. KEY RESULTS Four days of pentoxifylline treatment slightly increased liver lipids in ob/ob mice. After 3 weeks, pentoxifylline exacerbated fatty liver and plasma transaminases in ob/ob mice but did not induce liver steatosis in lean mice. Plasma glucose was highest in fed, but not fasted, ob/ob mice treated with pentoxifylline. During the first 10 min of an oral glucose tolerance test, blood glucose increased more rapidly in pentoxifylline-treated mice. Jejunal expression of glucose transporter 2 isoform was increased in pentoxifylline-treated obese mice. Hepatic activity of carbohydrate response element binding protein (ChREBP) increased after pentoxifylline in ob/ob, but not lean, mice. Hepatic expression of lipogenic enzymes was highest in pentoxifylline-treated ob/ob mice. However, pentoxifylline reduced markers of oxidative stress and inflammation in ob/ob liver. CONCLUSION AND IMPLICATIONS Pentoxifylline exacerbated fatty liver in ob/ob mice through enhanced intestinal glucose absorption, increased postprandial glycaemia and activation of hepatic lipogenesis. Long-term treatment with pentoxifylline could worsen fatty liver in some patients with pre-existing hyperglycaemia. PMID:21740407

  17. 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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2015-04-01

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

  20. 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

  1. 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.

  2. Vitamin D and intestinal calcium absorption.

    PubMed

    Christakos, Sylvia; Dhawan, Puneet; Porta, Angela; Mady, Leila J; Seth, Tanya

    2011-12-05

    The principal function of vitamin D in calcium homeostasis is to increase calcium absorption from the intestine. Calcium is absorbed by both an active transcellular pathway, which is energy dependent, and by a passive paracellular pathway through tight junctions. 1,25Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) the hormonally active form of vitamin D, through its genomic actions, is the major stimulator of active intestinal calcium absorption which involves calcium influx, translocation of calcium through the interior of the enterocyte and basolateral extrusion of calcium by the intestinal plasma membrane pump. This article reviews recent studies that have challenged the traditional model of vitamin D mediated transcellular calcium absorption and the crucial role of specific calcium transport proteins in intestinal calcium absorption. There is also increasing evidence that 1,25(OH)(2)D(3) can enhance paracellular calcium diffusion. The influence of estrogen, prolactin, glucocorticoids and aging on intestinal calcium absorption and the role of the distal intestine in vitamin D mediated intestinal calcium absorption are also discussed.

  3. [Effect of carbachol on intestinal mucosa blood flow and absorption rate of glucose-electrolyte solution during enteral resuscitation for 50% total body surface area full-thickness burn injury in dog].

    PubMed

    Hu, Sen; Che, Jin-wei; Du, Ying; Bao, Cheng-mei; Tian, Yi-jun; Wang, Lei; Geng, Shi-jia; Wu, Jing; Sheng, Zhi-yong

    2008-03-01

    To investigate the effect of carbachol (CAR) on blood flow of intestinal mucosa and absorption rate of glucose-electrolyte solution (GES) during enteral resuscitation of burn shock in dog. Eighteen male Beagle dogs were subjected to a (51.2+/-2.6)% total body surface area (TBSA) full-thickness flame injury, and fluid resuscitation was given according to Parkland formula 0.5 hour after burn. Animals were randomly divided into intravenous infusion of GES group (VGES group, n=6), enteral infusion of GES group (EGES group, n=6) and EGES containing 0.25 microg/kg of CAR group (EGES/CAR group n=6). In the first 8 hours post burn, intestinal absorption rate of water and Na+, intestinal mucosa blood flow (IBF), the plasma volume (PV) and plasma concentration of Na+ were continuously determined without anesthesia. At the end of 8 hours animals were sacrificed, and specimens of gut tissue were taken to determine the activity of Na+-K+-ATPase. The intestinal absorption rate of water and Na+ was reduced markedly after burn in two enteral resuscitation groups and much lower than pre-injury levels and the expected infusing rate according to Parkland formula. It was found that the absorption rate of water and Na+ from 1.5 hours and 2.5 hours in EGES/CAR group were significantly higher compared with those in EGES group (all P<0.05). During 8 hours after burn, only 47.1% and 63.8% of fluids enterally infused in EGES and EGES/CAR groups were absorbed by the gut. The volume of fluid absorbed and the fluid absorption rate were significantly higher in EGES/CAR group than those in EGES group (P<0.05). Incidence of gut intolerance (diarrhea) was 83% in EGES group, which was higher than that of in EGES/CAR group (50%). IBF was significantly decreased compared with pre-injury levels in all groups. Enteral infusion of CAR led to a significant elevation of IBF in EGES/CAR compared with GES group from 4 hours after burn, but it was still lower than pre-injury levels and those in VGES group

  4. Effect of glycine and glucose on sodium and water absorption in patients with cholera

    PubMed Central

    Nalin, D. R.; Cash, R. A.; Rahman, M.; Yunus, Md.

    1970-01-01

    Electrolyte solutions containing glucose, glycine, or a combination of the two were absorbed sufficiently well from the intestine to supply maintenance fluid and the electrolytes required by cholera patients. Data on net absorption and duration and volume of diarrhoea show that a solution containing both glucose and glycine provides more effective therapy than solutions containing either glucose or glycine alone. PMID:5473608

  5. Inhibitory effect of palatinose on glucose absorption in everted rat gut.

    PubMed

    Kashimura, Jun; Nagai, Yukie

    2007-02-01

    We previously reported that the increase in blood glucose was more suppressed when palatinose was taken with sucrose or glucose than when either of these sugars was taken alone. In the present study, we examined whether or not palatinose suppresses glucose absorption using everted intestinal sacs from rats. Glucose absorption in the everted rat intestinal sac was measured with 0, 1, 2.5 or 5 mM of palatinose added to 20 mM glucose. The measurement was repeated five times for each palatinose level to calculate a mean value. The result showed glucose absorption to be reduced as the palatinose level increased. It was significantly reduced when 5 mM palatinose was added as compared with no palatinose addition (p<0.05). These results suggest that palatinose suppresses glucose absorption.

  6. Intestinal absorption and metabolism of xenobiotics

    PubMed Central

    Chhabra, Rajendra S.

    1979-01-01

    There are five possible processes of intestinal absorption of xenobiotics. These are active transport, passive diffusions, pinocytosis, filtration through “pores,” and lymphatic absorption. The passive diffusion is major process for transport of foreign chemicals across the intestine. Though the lymphatic absorption of drugs is not of any major therapeutic significance, the uptake of toxic chemicals such as 3-MC, benzpyrene, and DDT through lymphatics may enhance their toxicity, since they are distributed to other organ systems in the body without being metabolized by liver. A number of factors such as diet, motility of intestine, interference with gastrointestinal flora, changes in the rate of gastric emptying, age of the animal, and dissolution rate of xenobiotic can alter the rate of absorption of chemicals. Liver is the major site of metabolism of xenobiotics, but the contribution of intestinal metabolism of xenobiotic can influence the overall bioavailability of chemicals. The xenobiotic metabolizing enzymes located in endoplasmic reticulum of intestine possess biochemical characteristics similar to that of liver. In general, the rate of metabolism of xenobiotics by intestinal microsomal preparation is lower than that observed with similar hepatic microsomal preparations. The in vitro intestinal metabolism of xenobiotics is affected by several factors including age, sex, diurnal variations, species, and nutritional status of the animal. The intestinal xenobiotic metabolizing enzymes are stimulated by the pretreatment of animals with foreign chemicals, but this depends on the route of administration of chemicals, drug substrate and the animal species used. Rabbit intestinal drug metabolizing enzymes seem to be resistant to induction by foreign chemicals. PMID:540626

  7. Chromium absorption in the vascularly perfused rat intestine

    SciTech Connect

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

    1986-03-01

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

  8. Circadian regulators of intestinal lipid absorption

    PubMed Central

    Hussain, M. Mahmood; Pan, Xiaoyue

    2015-01-01

    Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption. PMID:25057097

  9. Glucose absorption by a nectarivorous bird: the passive pathway is paramount.

    PubMed

    Karasov, W H; Cork, S J

    1994-07-01

    We tested the hypothesis that most sugar absorption across the small intestine's brush border is normally by a mediated pathway, i.e., the Na(+)-glucose cotransporter. In nectar-eating rainbow lorikeets (Trichoglossus haematodus, 120 g), we measured mediated D-glucose uptake in vitro using the everted-sleeve technique. The apparent Michaelis constant (7.7 mM) was similar to that observed in hummingbirds and other birds in general. Maximal mediated D-glucose uptake summed along the entire length of intestine (48 cm) was not notably high (5.34 mumol/min) when compared with other avian species and was an order of magnitude too low to explain observed rates of glucose absorption in vivo (54.5 mumol/min). This implied that nonmediated glucose absorption predominated, and independent verification of that was sought. We applied a pharmacokinetic technique to measure in vivo absorption of L-glucose, the stereoisomer that does not interact with the Na(+)-glucose cotransporter. Eighty percent of L-glucose that was ingested was absorbed, confirming that nonmediated absorption can be substantial. We discuss how equating L-glucose absorption with passive D-glucose absorption depends on certain assumptions regarding the relative importance of diffusive and convective passive flux. In either case, the conclusion about the relative importance of passive absorption should still hold.

  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. 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

  12. [Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations].

    PubMed

    Liu, Ying; Yi, Tao; Di, Huan; Xiao, Lu; He, Ji-Kui

    2011-08-01

    A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.

  13. Expression of sweet receptor components in equine small intestine: relevance to intestinal glucose transport.

    PubMed

    Daly, Kristian; Al-Rammahi, Miran; Arora, Daleep K; Moran, Andrew W; Proudman, Christopher J; Ninomiya, Yuzo; Shirazi-Beechey, Soraya P

    2012-07-15

    The heteromeric sweet taste receptor T1R2-T1R3 is expressed on the luminal membrane of certain populations of enteroendocrine cells. Sensing of sugars and other sweet compounds by this receptor activates a pathway in enteroendocrine cells, resulting in secretion of a number of gut hormones, including glucagon-like peptide 2 (GLP-2). This subsequently leads to upregulation in the expression of intestinal Na(+)/glucose cotransporter, SGLT1, and increased intestinal glucose absorption. On the basis of the current information available on the horse genome sequence, it has been proposed that the gene for T1R2 (Tas1R2) is absent in the horse. We show here, however, that horses express both the mRNA and protein for T1R2. Equine T1R2 is most closely homologous to that in the pig and the cow. T1R2 protein, along with T1R3, α-gustducin, and GLP-2 proteins are coexpressed in equine intestinal endocrine cells. Intravenous administration of GLP-2, in rats and pigs, leads to an increase in the expression of SGLT1 in absorptive enterocytes and enhancement in blood glucose concentrations. GLP-2 receptor is expressed in enteric neurons, excluding the direct effect of GLP-2 on enterocytes. However, electric stimulation of enteric neurons generates a neural response leading to SGLT1 upregulation, suggesting that sugar in the intestine activates a reflex increase in the functional expression of SGLT1. Horses possess the ability to upregulate SGLT1 expression in response to increased dietary carbohydrates, and to enhance the capacity of the gut to absorb glucose. The gut sweet receptor provides an accessible target for manipulating the equine gut to absorb glucose (and water), allowing greater energy uptake and hydration for hard-working horses.

  14. Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea.

    PubMed Central

    Keating, J; Bjarnason, I; Somasundaram, S; Macpherson, A; Francis, N; Price, A B; Sharpstone, D; Smithson, J; Menzies, I S; Gazzard, B G

    1995-01-01

    Intestinal function is poorly defined in patients with HIV infection. Absorptive capacity and intestinal permeability were assessed using 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in 88 HIV infected patients and the findings were correlated with the degree of immunosuppression (CD4 counts), diarrhoea, wasting, intestinal pathogen status, and histomorphometric analysis of jejunal biopsy samples. Malabsorption of 3-O-methyl-D-glucose and D-xylose was prevalent in all groups of patients with AIDS but not in asymptomatic, well patients with HIV. Malabsorption correlated significantly (r = 0.34-0.56, p < 0.005) with the degree of immune suppression and with body mass index. Increased intestinal permeability was found in all subgroups of patients. The changes in absorption-permeability were of comparable severity to those found in patients with untreated coeliac disease. Jejunal histology, however, showed only mild changes in the villus height/crypt depth ratio as compared with subtotal villus atrophy in coeliac disease. Malabsorption and increased intestinal permeability are common in AIDS patients. Malabsorption, which has nutritional implications, relates more to immune suppression than jejunal morphological changes. PMID:8549936

  15. 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…

  16. 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…

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

    PubMed Central

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

    2013-01-01

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

  18. Biotin absorption by distal rat intestine

    SciTech Connect

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

    1987-12-01

    We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin.

  19. Flavonoids have differential effects on glucose absorption in rats (Rattus norvegicus) and American robins (Turdis migratorius).

    PubMed

    Skopec, Michele M; Green, Adam K; Karasov, William H

    2010-02-01

    Mounting evidence suggests that small birds rely largely on non-mediated intestinal absorption of glucose through the paracellular pathway, while non-flying mammals rely on mediated absorption across the enterocyte membranes by using glucose transporters SGLT-1 and GLUT-2. Relying on non-mediated transport of glucose may decrease its absorption rate at low glucose concentrations but may release small birds from the effects of glucose transport inhibitors. We evaluated transport by using flavonoids known to inhibit glucose transport in vitro. Quercetin, isoquercetrin, and phloridzin were tested in rats (Rattus norvegicus) and robins (Turdis migratirius), and naringenin, naringenin-7-glucoside, genistein, epigallocatechin gallate (EGCG), and phloretin were used only in rats. By using a pharmacokinetic approach that involves serial blood collection and area under the curve calculations, we determined the bioavailability of 3-0-methyl D-glucose, the non-metabolized analogue of D-glucose. Six of the eight flavonoids tested in rats significantly decreased the absorption of 3-0-methyl D-glucose, while none of the flavonoids tested in robins significantly decreased the bioavailability of 3-0-methyl D-glucose. We conclude that flavonoids effectively decrease glucose absorption in rats, which rely on mediated absorption of glucose, but that flavonoids do not have an effect in robins, which rely on non-mediated absorption of glucose.

  20. Intestinal absorption of aluminium in renal failure.

    PubMed

    Drüeke, Tilman B

    2002-01-01

    The proportion of the daily ingested aluminium that is absorbed in the intestinal tract has remained a matter of debate for many years because no reliable method of measurement was available. Studies with earlier analytic techniques reported fractional absorption of aluminium from as little as 0.001% to as much as 27% of an oral dose. Measurement of (26)Al by high-energy accelerator mass spectrometry has permitted more accurate analyses. In normal young rats, 0.05-0.1% of ingested aluminium is absorbed in the intestine, of which roughly half goes to the skeleton within 2 h, whereas the remaining half is excreted in the urine, most of it within 48 h. Deposition in organs other than the skeleton appears to be negligible. In healthy human volunteers, the most recent estimates of fractional intestinal (26)Al absorption were also in the range of 0.06-0.1%. In both rats and humans, intestinal absorption of aluminium is subject to many systemic and local factors. The latter include various compounds with which aluminium is complexed in the gut lumen, and gastric acidity. The influence of food is controversial; however, absorption appears higher in the fasted than the post-prandial state. Luminal phosphate concentration decreases aluminium absorption, whereas citrate increases it. For theoretical reasons, silicates should prevent aluminium absorption, but experimental evidence has not supported this theory. Whether water hardness affects aluminium bioavailability remains a matter of debate. General conditions may also modify aluminium absorption and deposition in bone. Examples of these general factors include the uraemic syndrome, diabetes mellitus, secondary hyperparathyroidism, vitamin D status, Alzheimer's disease and Down's syndrome. Awareness of intestinal absorption of aluminium is particularly important, given that aluminium-based binders continue to be used in uraemic patients, despite the hazards of aluminium accumulation. The lessons we have learned about

  1. Upregulation of intestinal glucose transporters after Roux-en-Y gastric bypass to prevent carbohydrate malabsorption.

    PubMed

    Nguyen, Nam Q; Debreceni, Tamara L; Bambrick, Jenna E; Chia, Bridgette; Deane, Adam M; Wittert, Gary; Rayner, Chris K; Horowitz, Michael; Young, Richard L

    2014-10-01

    To determine the effect of Roux-en-Y gastric bypass (RYGB) on the expression of intestinal sweet taste receptors (STRs), glucose transporters (GTs), glucose absorption, and glycemia. Intestinal biopsies were collected for mRNA expression of STR (T1R2) and GTs (SGLT-1 and GLUT2) from 11 non-diabetic RYGB, 13 non-diabetic obese, and 11 healthy subjects, at baseline and following a 30 min small intestinal (SI) glucose infusion (30 g/150 ml water with 3 g 3-O-methyl-d-glucopyranose (3-OMG)). Blood glucose, plasma 3-OMG, and insulin were measured for 270 min. In RYGB patients, expression of both GTs was ∼2-fold higher at baseline and after glucose infusion than those of morbidly obese or healthy subjects (P < 0.001). STR expressions were comparable amongst the groups. Peak plasma 3-OMG in both RYGB (r = 0.69, P = 0.01) and obese (r = 0.72, P = 0.005) correlated with baseline expression of SGLT-1, as was the case with peak blood glucose in RYGB subjects (r = 0.69, P = 0.02). The upregulated intestinal GTs in RYGB patients are associated with increased glucose absorption when glucose is delivered at a physiological rate, suggesting a molecular adaptation to prevent carbohydrate malabsorption from rapid intestinal transit after RYGB. Copyright © 2014 The Obesity Society.

  2. [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.

  3. 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.

  4. Physiology of Intestinal Absorption and Secretion

    PubMed Central

    Kiela, Pawel R.; Ghishan, Fayez K.

    2016-01-01

    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, lipidand 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

  5. Intestinal absorption of calcium and phosphorus

    SciTech Connect

    Wasserman, R.H.

    1981-01-01

    The intestinal absorption of calcium and phosphorus has received considerable attention in recent years. The evidence has clearly indicated that calcium is absorbed by two processes: active transport and diffusion. Vitamin D appears to affect both processes, and has a significant effect at the brush border of the intestinal cell. Several proposed models to account for the transmural movement of calcium are discussed. The active transport of phosphate is under the control of vitamin D and is located at the brush border region of the intestinal cell. This transport system, like several others, appears to be sodium-dependent and inhibited by ouabain. In-transit phosphate does not mix with the cellular phosphate pool. Emphasized in the presentation is current knowledge of the transport mechanisms and macromolecular changes that potentially account for the stimulatory effect of vitamin D on calcium and phosphate transport.

  6. Iron absorption by small intestine of chickens.

    PubMed

    Sáiz, M P; Martí, M T; Mitjavila, M T; Planas, J

    1993-01-01

    Iron (Fe) absorption by three segments (duodenum, jejunum, and ileum) of the small intestine of chickens was studied by a perfusion technique in vivo in closed circuit using 59Fe Cl3 and was related to the histological characteristics of each segment. The serosal transfers of Fe for the duodenum and jejunum were the same (14%/cm), but significantly different (p < 0.05) from those of the ileum (9%/cm), which may be explained by the morphological and histological properties of the gut of chickens. However, the presence of Fe in blood and in liver was significantly lower after perfusion of the jejunum and ileum than after perfusion of the duodenum. It is concluded that chickens show an early adaptation of small intestine to Fe absorption in response to the considerable loss of Fe suffered during the laying process.

  7. Dietary Phospholipids and Intestinal Cholesterol Absorption

    PubMed Central

    Cohn, Jeffrey S.; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W. S.; Tandy, Sally

    2010-01-01

    Experiments carried out with cultured cells and in experimental animals have consistently shown that phospholipids (PLs) can inhibit intestinal cholesterol absorption. Limited evidence from clinical studies suggests that dietary PL supplementation has a similar effect in man. A number of biological mechanisms have been proposed in order to explain how PL in the gut lumen is able to affect cholesterol uptake by the gut mucosa. Further research is however required to establish whether the ability of PLs to inhibit cholesterol absorption is of therapeutic benefit. PMID:22254012

  8. Disorders of intestinal secretion and absorption.

    PubMed

    Schulzke, Jörg-Dieter; Tröger, Hanno; Amasheh, Maren

    2009-01-01

    The gastrointestinal tract possesses a huge epithelial surface area and performs many different tasks. Amongst them are the digestive and absorptive functions. Disorders of intestinal absorption and secretion comprise a variety of different diseases, e.g. coeliac disease, lactase deficiency or Whipple's disease. In principle, impaired small intestinal function can occur with or without morphological alterations of the intestinal mucosa. Therefore, in the work up of a malabsorptive syndrome an early small intestinal biopsy is encouraged in conjunction with breath tests and stool analysis to guide further management. In addition, there is an array of functional tests, the clinical availability of which becomes more and more limited. In any case, early diagnosis of the underlying pathophysiology is most important, in order to initiate proper therapy. In this chapter, diagnostic procedure of malabsorption is discussed with special attention to specific disease like coeliac disease, Whipple's disease, giardiasis and short bowel syndrome. Furthermore, bacterial overgrowth, carbohydrate malabsorption and specific nutrient malabsorption (e.g. for iron or vitamins) and protein-losing enteropathy are presented with obligatory and optional tests as used in the clinical setting.

  9. 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.

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

    PubMed Central

    Naftalin, Richard J.

    2016-01-01

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

  11. 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

  12. Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption.

    PubMed

    Hui, David Y; Labonté, Eric D; Howles, Philip N

    2008-04-01

    Intestinal cholesterol absorption is modulated by transport proteins in enterocytes. Cholesterol uptake from intestinal lumen requires several proteins on apical brush-border membranes, including Niemann-Pick C1-like 1 (NPC1L1), scavenger receptor B-I, and CD36, whereas two ATP-binding cassette half transporters, ABCG5 and ABCG8, on apical membranes work together for cholesterol efflux back to the intestinal lumen to limit cholesterol absorption. NPC1L1 is essential for cholesterol absorption, but its function as a cell surface transporter or an intracellular cholesterol transport protein needs clarification. Another ATP transporter, ABCA1, is present in the basolateral membrane to mediate HDL secretion from enterocytes.

  13. Modulation of intestinal glucose transport in response to reduced nitrogen supply in young goats.

    PubMed

    Muscher-Banse, A S; Piechotta, M; Schröder, B; Breves, G

    2012-12-01

    The reduction of dietary protein is a common approach in ruminants to decrease the excretion of N because ruminants are able to recycle N efficiently by the rumino-hepatic circulation. In nonruminant species an impact on other metabolic pathways such as glucose metabolism was observed when dietary protein intake was reduced. However, an impact of dietary N reduction in goats on glucose metabolism especially on intestinal glucose absorption is questionable because ruminants have very efficient endogenous recycling mechanisms. Therefore, the aim of the present study was to characterize the intestinal absorption of glucose in growing goats kept on different N supply under isoenergetic conditions. The different CP concentrations (20, 16, 10, 9, and 7% CP) of the experimental diets were adjusted by adding urea to the rations. Intestinal flux rates of glucose were determined by Ussing chamber experiments. For a more mechanistic approach, the Na(+)-dependent uptake of glucose into intestinal brush-border membrane vesicles (BBMV) and the expression patterns of the Na(+)-dependent glucose transporter SGLT1 and the glucose transporter 2 (GLUT2) were determined. Reduced N intake resulted in a decrease of plasma glucose (P < 0.001) and insulin (P = 0.004) concentrations whereas the intestinal flux rates of glucose were elevated (P < 0.001), which were inhibited by phlorizin. However, the uptake of glucose into intestinal BBMV was not changed whereas the expression of SGLT1 on mRNA (P < 0.05) and protein abundance (P = 0.03) was decreased in response to a reduced N intake. The mRNA expression of GLUT2 was not affected. From these data, it can be concluded that the intestinal absorption of glucose was modulated by changes in dietary N intake. It is suggested that intracellular metabolism or basolateral transport systems or both might be activated during this feeding regimen because the apical located SGLT1 might not be involved. Therefore, an impact of dietary N reduction on

  14. Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs.

    PubMed

    Massimino, S P; McBurney, M I; Field, C J; Thomson, A B; Keelan, M; Hayek, M G; Sunvold, G D

    1998-10-01

    Ileal proglucagon gene expression and postprandial plasma concentrations of proglucagon-derived peptides are reported to change with the type and quantity of dietary fiber ingested by rats. Within the intestine, proglucagon encodes several proglucagon-derived peptides known to modulate intestinal absorption capacity and pancreatic insulin secretion. To determine whether the chronic ingestion of fermentable dietary fiber regulates the expression and synthesis of proglucagon-derived peptides in the distal intestine to modulate glucose homeostasis, the following study was conducted: 16 adult dogs (23 +/- 2 kg) were fed isoenergetic, isonitrogenous diets containing a mixture of high fermentable dietary fibers (HFF) or low fermentable (LFF) wood cellulose for 14 d in a randomized cross-over design. Food was withheld for 16 h before an oral glucose tolerance test was conducted supplying 2 g of glucose/kg body wt, and peripheral blood was collected via a hind-leg catheter at 0, 15, 30, 45, 60, 90 and 120 min for plasma glucose, insulin and glucagon-like peptide-1(7-36)NH2 (GLP-1) analyses. Intestinal samples were collected after the second dietary treatment. Ileal proglucagon mRNA, intestinal (GLP-1) concentrations and the integrated area under the curves (AUC) for plasma GLP-1 and insulin were greater and plasma glucose AUC was reduced when dogs were fed the HFF diet compared to the LFF diet (P < 0.05). Intestinal villi heights, brush border and basolateral glucose transporter protein abundance and jejunal transport capacities were significantly greater when dogs were fed the HFF diet than when fed the LFF diet. In conclusion, improvements in glucose homeostasis are observed in healthy dogs when they ingest fermentable fibers.

  15. The digestive adaptation of flying vertebrates: high intestinal paracellular absorption compensates for smaller guts.

    PubMed

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

    2007-11-27

    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.

  16. Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test.

    PubMed

    Salinari, Serenella; Bertuzzi, Alessandro; Mingrone, Geltrude

    2011-06-01

    The rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.

  17. 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.

  18. Intestinal absorption of biotin in the rat

    SciTech Connect

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

    1986-07-01

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

  19. Transporters involved in glucose and water absorption in the Dysdercus peruvianus (Hemiptera: Pyrrhocoridae) anterior midgut.

    PubMed

    Bifano, Thaís D; Alegria, Thiago G P; Terra, Walter R

    2010-09-01

    Little is known about insect intestinal sugar absorption, in spite of the recent findings, and even less has been published regarding water absorption. The aim of this study was to shed light on putative transporters of water and glucose in the insect midgut. Glucose and water absorptions by the anterior ventriculus of Dysdercus peruvianus midgut were determined by feeding the insects with a glucose and a non-absorbable dye solution, followed by periodical dissection of insects and analysis of ventricular contents. Glucose absorption decreases glucose/dye ratios and water absorption increases dye concentrations. Water and glucose transports are activated (water 50%, glucose 33%) by 50 mM K(2)SO(4) and are inhibited (water 46%, glucose 82%) by 0.2 mM phloretin, the inhibitor of the facilitative hexose transporter (GLUT) or are inhibited (water 45%, glucose 35%) by 0.1 mM phlorizin, the inhibitor of the Na(+)-glucose cotransporter (SGLT). The results also showed that the putative SGLT transports about two times more water relative to glucose than the putative GLUT. These results mean that D. peruvianus uses a GLUT-like transporter and an SGLT-like transporter (with K(+) instead of Na(+)) to absorb dietary glucose and water. A cDNA library from D. peruvianus midgut was screened and we found one sequence homologous to GLUT1, named DpGLUT, and another to a sodium/solute symporter, named DpSGLT. Semi-quantitative RT-PCR studies revealed that DpGLUT and DpSGLTs mRNA were expressed in the anterior midgut, where glucose and water are absorbed, but not in fat body, salivary gland and Malpighian tubules. This is the first report showing the involvement of putative GLUT and SGLT in both water and glucose midgut absorption in insects.

  20. Intestinal Absorption of Immunoglobulins by Newborn Infants

    PubMed Central

    Iyengar, Leela; Selvaraj, R. J.

    1972-01-01

    Intestinal absorption in newborn infants of immunoglobulins present in colostrum was studied by measuring the concentrations of immunoglobulins IgA, IgG, and IgM in cord blood and following the changes in the serum of the infant on the 5th day after birth. In infants who did not receive colostrum, a marked fall in IgG levels was observed on the 5th day after birth as compared to levels at birth. The concentrations of IgA and IgM showed marginal changes. In contrast, colostrumfed infants showed significant increases in the concentration of IgG. Levels of all 3 immunoglobulins on the 5th day were significantly higher in the serum of colostrumfed infants as compared to those who did not receive colostrum. It is suggested that immunoglobulins present in colostrum are to some extent absorbed from the intestinal tract of newborn infants, and this may have some physiological significance in the resistance to infection during the early neonatal period. PMID:4624594

  1. Intestinal absorption and histomorphometry of Syrian hamsters (Mesocricetus auratus) experimentally infected with Lawsonia intracellularis.

    PubMed

    Vannucci, Fabio Augusto; Borges, Elizabeth Lage; de Oliveira, Juliana Saes Vilaça; Guedes, Roberto Mauricio Carvalho

    2010-10-26

    The objective of this study was to evaluate the intestinal absorption and histomorphometry of hamsters experimentally infected with Lawsonia intracellularis and correlate these parameters with severity of infection based on immunohistochemistry. Sixty hamsters were equally divided into control and inoculated groups which were orally infected with intestinal mucosa homogenate from pigs naturally infected with L. intracellularis. The intestinal absorption of glucose, sodium, potassium and chloride was evaluated in live animals (25 inoculated and 25 control) on day 26 after inoculation. In this procedure, a standard solution was infused into the cranial jejunum and collected at the terminal ileum. The experimental infection was confirmed by gross and histopathological examination and L. intracellularis antigen labeling by immunohistochemistry. Histomorphometry analysis demonstrated positive correlation between intestinal crypt depth and severity of infection based on immunohistochemistry. Infected animals had significantly lower intestinal absorption of glucose, potassium and chloride. These results indicate a lower intestinal absorption as an important mechanism of diarrhea in hamsters experimentally infected with L. intracellularis. Therefore, malabsorption should be considered as the main mechanism involved in the physiopathology of the diarrhea in L. intracellularis infected animals.

  2. INTESTINAL TRIGLYCERIDE ABSORPTION IN THE RAT

    PubMed Central

    Cardell, Robert R.; Badenhausen, Susan; Porter, Keith R.

    1967-01-01

    This report provides information on the morphology of fat absorption in rat intestinal epithelial cells. Three types of experiments were performed: (a) intubation of corn oil into fasted rats, (b) injection of physiological fatty-chyme prepared from fat-fed donor rats into ligated segments of jejunum of fasted animals, and (c) administration of electron-opaque particles in corn oil and markers given concurrently with the fat. These results support the hypothesis that fat is absorbed by selective diffusion of monoglycerides and fatty acids from micelles rather than by pinocytosis of unhydrolized triglycerides. Evidence is presented that the pits between the microvilli, previously believed to function in the transport of fat, are not involved in this process. Instead they appear to contribute their contents to lysosomes in the apical cytoplasm. Arguments are offered that the monoglycerides and fatty acids diffuse from the micelle while the latter is associated with the microvillous membrane of the absorptive cell. These micellar components penetrate the plasma membrane and diffuse into the cytoplasmic matrix where they encounter the SER. Triglyceride synthesis occurs in the SER and results in the deposition of fat droplets within its lumina. The synthesis of triglycerides and their sequestration into the SER establishes an inward diffusion gradient of monoglycerides and fatty acids. PMID:6033529

  3. Disrupted circadian rhythmicity of the intestinal glucose transporter SGLT1 in Zucker diabetic fatty rats.

    PubMed

    Bhutta, Hina Y; Deelman, Tara E; Ashley, Stanley W; Rhoads, David B; Tavakkoli, Ali

    2013-06-01

    Intestinal absorptive capacity shows a circadian rhythm synchronized with eating patterns. Disrupting these coordinated rhythms, e.g., with shift work, may contribute to metabolic disease. Circadian expression of nutrient transporters has not been studied in metabolic disease. We studied the circadian rhythm of intestinal transporter sodium glucose co-transporter type 1 (SGLT1) in an obese diabetic rat. We compared obese Zucker diabetic fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0 = 7:00 a.m.) 3, 9, or 15 to measure insulin resistance, SGLT1 expression and intestinal glucose absorption capacity. Regulators of SGLT1 (sweet taste receptor T1R2/3; clock genes) were measured to elucidate underlying mechanisms. Both groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats maintained rhythmicity of SGLT1 mRNA expression but that of functional glucose absorption was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups. Neither group had discernible rhythms of intestinal GLUT2 (glucose transporter) or T1R2 (sweet taste receptor component) mRNA expression. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding. Glucose intolerance was evident in lean rats, but only obese rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and function. Our findings suggest that disrupted circadian feeding rhythms contribute to glucose intolerance, but additional factors (genetics, changes in nutrient sensing/transport) are needed to lead to full diabetes.

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

    SciTech Connect

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

    1987-03-01

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

  5. Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes.

    PubMed

    Alskär, Oskar; Bagger, Jonatan I; Røge, Rikke M; Knop, Filip K; Karlsson, Mats O; Vilsbøll, Tina; Kjellsson, Maria C

    2016-03-01

    The integrated glucose-insulin (IGI) model is a previously published semimechanistic model that describes plasma glucose and insulin concentrations after glucose challenges. The aim of this work was to use knowledge of physiology to improve the IGI model's description of glucose absorption and gastric emptying after tests with varying glucose doses. The developed model's performance was compared to empirical models. To develop our model, data from oral and intravenous glucose challenges in patients with type 2 diabetes and healthy control subjects were used together with present knowledge of small intestinal transit time, glucose inhibition of gastric emptying, and saturable absorption of glucose over the epithelium to improve the description of gastric emptying and glucose absorption in the IGI model. Duodenal glucose was found to inhibit gastric emptying. The performance of the saturable glucose absorption was superior to linear absorption regardless of the gastric emptying model applied. The semiphysiological model developed performed better than previously published empirical models and allows better understanding of the mechanisms underlying glucose absorption. In conclusion, our new model provides a better description and improves the understanding of dynamic glucose tests involving oral glucose.

  6. 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.

  7. Glucose absorption kinetics in Zambian African patients with and without systemic bacterial infections

    PubMed Central

    Cook, G. C.

    1971-01-01

    Using a double-lumen tube perfusion system, solutions of glucose (1·0, 2·5, and 5·0 g 100ml−1) have been perfused into the upper jejunum of 22 Zambian African subjects in order to study their glucose absorption kinetics. None of them had clinical evidence of malnutrition or intestinal disease. In 10 there was no evidence of an infective disease (`normal' group); seven had tuberculosis; five had acute bacterial infections. The mean serum albumin concentration was significantly lower in those with infections; the mean total and γ-globulin concentrations were significantly higher in the tuberculosis group. There was good reproducibility in triplicate assessments of glucose and water absorption rates in the individual subjects. Despite a wide scatter, the mean glucose kinetic curves were significantly flatter in those with infections than in the normal group (p<0·02). There was a significant association between glucose and water absorption rates in the individuals. D-xylose absorption was estimated in 11 subjects and there was a significant correlation between that and the glucose absorption rate. Jejunal morphology (n=9) and disaccharidase concentrations (n=6) were normal for African subjects and there were no significant associations between either of those and the absorption rates. Galactose absorption kinetics have been studied in an additional four relatively normal Zambian Africans. This study suggests that systemic bacterial infections can produce malabsorption. This may be relevant to the weight loss in patients with pulmonary tuberculosis and also to the aetiology of kwashiorkor. PMID:4110099

  8. 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.

  9. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase.

    PubMed

    Brun, Lucas R; Brance, María L; Lombarte, Mercedes; Lupo, Maela; Di Loreto, Verónica E; Rigalli, Alfredo

    2014-07-01

    Intestinal alkaline phosphatase is a brush border enzyme that is stimulated by calcium. Inhibition of intestinal alkaline phosphatase increases intestinal calcium absorption. We hypothesized that intestinal alkaline phosphatase acts as a minute-to-minute regulatory mechanism of calcium entry. The aim of this study was to evaluate the mechanism by which intestinal luminal calcium controls intestinal calcium absorption. We performed kinetic studies with purified intestinal alkaline phosphatase and everted duodenal sacs and showed that intestinal alkaline phosphatase modifies the luminal pH as a function of enzyme concentration and calcium luminal content. A decrease in pH occurred simultaneously with a decrease in calcium absorption. The inhibition of intestinal alkaline phosphatase by l-phenylalanine caused an increase in calcium absorption. This effect was also confirmed in calcium uptake experiments with isolated duodenal cells. Changes in luminal pH arising from intestinal alkaline phosphatase activity induced by luminal calcium concentration modulate intestinal calcium absorption. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Comparative absorption of [13C]glucose and [13C]lactose by premature infants.

    PubMed

    Murray, R D; Boutton, T W; Klein, P D; Gilbert, M; Paule, C L; MacLean, W C

    1990-01-01

    Oxidation of orally administered [13C]glucose and [13C]lactose and fecal recovery of malabsorbed substrates were determined in two groups of premature infants. Eighteen studies were performed with six infants at Johns Hopkins Hospital (JHH); 24 studies were performed with nine infants at Columbus Children's Hospital (CCH). The two groups differed in that JHH infants had shorter gestations but were older when studied. Fecal 13C loss after [13C]glucose administration did not differ between the two groups. Compared with glucose, the metabolism of lactose appeared to involve more malabsorption and colonic fermentation in JHH infants than in CCH infants and resulted in higher fecal losses of substrate carbon. Maturation appeared to involve increased proximal intestinal absorption and greater retention of absorbed carbohydrate. Simultaneous absorption of substrate from the small and large intestine may limit the usefulness of breath tests for 13C in the premature infant.

  11. Intravenous Glucose Acutely Stimulates Intestinal Lipoprotein Secretion in Healthy Humans.

    PubMed

    Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Lewis, Gary F

    2016-07-01

    Increased production of intestinal triglyceride-rich lipoproteins (TRLs) contributes to dyslipidemia and increased risk of atherosclerotic cardiovascular disease in insulin resistance and type 2 diabetes. We have previously demonstrated that enteral glucose enhances lipid-stimulated intestinal lipoprotein particle secretion. Here, we assessed whether glucose delivered systemically by intravenous infusion also enhances intestinal lipoprotein particle secretion in humans. On 2 occasions, 4 to 6 weeks apart and in random order, 10 healthy men received a constant 15-hour intravenous infusion of either 20% glucose to induce hyperglycemia or normal saline as control. Production of TRL-apolipoprotein B48 (apoB48, primary outcomes) and apoB100 (secondary outcomes) was assessed during hourly liquid-mixed macronutrient formula ingestion with stable isotope enrichment and multicompartmental modeling, under pancreatic clamp conditions to limit perturbations in pancreatic hormones (insulin and glucagon) and growth hormone. Compared with saline infusion, glucose infusion induced both hyperglycemia and hyperinsulinemia, increased plasma triglyceride levels, and increased TRL-apoB48 concentration and production rate (P<0.05), without affecting TRL-apoB48 fractional catabolic rate. No significant effect of hyperglycemia on TRL-apoB100 concentration and kinetic parameters was observed. Short-term intravenous infusion of glucose stimulates intestinal lipoprotein production. Hyperglycemia may contribute to intestinal lipoprotein overproduction in type 2 diabetes. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02607839. © 2016 American Heart Association, Inc.

  12. Intestinal perfusion indicates high reliance on paracellular nutrient absorption in an insectivorous bat Tadarida brasiliensis.

    PubMed

    Price, Edwin R; Brun, Antonio; Fasulo, Verónica; Karasov, William H; Caviedes-Vidal, Enrique

    2013-02-01

    Flying vertebrates have been hypothesized to have a high capacity for paracellular absorption of nutrients. This could be due to high permeability of the intestines to nutrient-sized molecules (i.e., in the size range of amino acids and glucose, MW 75-180 Da). We performed intestinal luminal perfusions of an insectivorous bat, Tadarida brasiliensis. Using radio-labeled molecules, we measured the uptake of two nutrients absorbed by paracellular and transporter-mediated mechanisms (L-proline, MW 115 Da, and D-glucose, MW 180 Da) and two carbohydrates that have no mediated transport (L-arabinose, MW 150 Da, and lactulose, MW 342 Da). Absorption of lactulose (0.61±0.06 nmol min(-1) cm(-1)) was significantly lower than that of the smaller arabinose (1.09±0.04 nmol min(-1) cm(-1)). Glucose absorption was significantly lower than that of proline at both nutrient concentrations (10mM and 75 mM). Using the absorption of arabinose to estimate the portion of proline absorption that is paracellular, we calculated that 25.1±3.0% to 66.2±7.8% of proline absorption is not transporter-mediated (varying proline from 1 mM to 75 mM). These results confirm our predictions that 1) paracellular absorption is molecule size selective, 2) absorption of proline would be greater than glucose absorption in an insectivore, and 3) paracellular absorption represents a large fraction of total nutrient absorption in bats.

  13. Disrupted circadian rhythmicity of the intestinal glucose transporter SGLT1 in Zucker Diabetic Fatty rats

    PubMed Central

    Bhutta, Hina Y.; Deelman, Tara E.; Ashley, Stanley W.; Rhoads, David B.; Tavakkoli, Ali

    2013-01-01

    Background Intestinal nutrient absorptive capacity shows a circadian rhythm synchronized with eating patterns. Studies have shown that disrupting these normally coordinated rhythms, e.g. with shift work, may contribute to metabolic disease. While circadian expression of many nutrient transporters has been studied in health, their rhythms in obesity and metabolic disorders is not known. We studied the circadian expression and function of intestinal glucose transporter SGLT1, a major glucose transporter, in a rodent model of obesity and diabetes. Methods We compared obese Zucker Diabetic Fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0=7am) 3, 9, or 15 to measure insulin resistance, SGLT1 (Sodium glucose co-transporter type 1) mRNA expression and intestinal glucose absorption capacity. Known regulators of SGLT1 expression (intestinal sweet taste receptor T1R2/3; clock genes) were also measured to elucidate underlying mechanisms. Results Both ZDF groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats had glucose levels less than half of the obese rats but were still hyperglycemic. Rhythmicity of mRNA expression was maintained but that of functional glucose uptake was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups while there was no discernible rhythm of intestinal glucose transporter gene GLUT2 expression or of the T1R2 component of the sweet taste receptor in either group. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding pattern. Glucose intolerance was evident in lean rats, but only obese ZDF rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and functional activity. Conclusions Our findings suggest that disrupted circadian feeding rhythms contribute to

  14. Models to predict intestinal absorption of therapeutic peptides and proteins.

    PubMed

    Antunes, Filipa; Andrade, Fernanda; Ferreira, Domingos; Nielsen, Hanne Morck; Sarmento, Bruno

    2013-01-01

    Prediction of human intestinal absorption is a major goal in the design, optimization, and selection of drugs intended for oral delivery, in particular proteins, which possess intrinsic poor transport across intestinal epithelium. There are various techniques currently employed to evaluate the extension of protein absorption in the different phases of drug discovery and development. Screening protocols to evaluate protein absorption include a range of preclinical methodologies like in silico, in vitro, in situ, ex vivo and in vivo. It is the careful and critical use of these techniques that can help to identify drug candidates, which most probably will be well absorbed from the human intestinal tract. It is well recognized that the human intestinal permeability cannot be accurately predicted based on a single preclinical method. However, the present social and scientific concerns about the animal well care as well as the pharmaceutical industries need for rapid, cheap and reliable models predicting bioavailability give reasons for using methods providing an appropriate correlation between results of in vivo and in vitro drug absorption. The aim of this review is to describe and compare in silico, in vitro, in situ, ex vivo and in vivo methods used to predict human intestinal absorption, giving a special attention to the intestinal absorption of therapeutic peptides and proteins.

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

    PubMed

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

    2009-07-01

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

  16. ApoA-IV: current and emerging roles in intestinal lipid metabolism, glucose homeostasis, and satiety.

    PubMed

    Kohan, Alison B; Wang, Fei; Lo, Chun-Min; Liu, Min; Tso, Patrick

    2015-03-15

    Apolipoprotein A-IV (apoA-IV) is secreted by the small intestine on chylomicrons into intestinal lymph in response to fat absorption. Many physiological functions have been ascribed to apoA-IV, including a role in chylomicron assembly and lipid metabolism, a mediator of reverse-cholesterol transport, an acute satiety factor, a regulator of gastric function, and, finally, a modulator of blood glucose homeostasis. The purpose of this review is to update our current view of intestinal apoA-IV synthesis and secretion and the physiological roles of apoA-IV in lipid metabolism and energy homeostasis, and to underscore the potential for intestinal apoA-IV to serve as a therapeutic target for the treatment of diabetes and obesity-related disease.

  17. Absorption sites of orally administered drugs in the small intestine.

    PubMed

    Murakami, Teruo

    2017-09-17

    In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

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

    PubMed Central

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

    2013-01-01

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

  19. Sweet-taste receptors, low-energy sweeteners, glucose absorption and insulin release.

    PubMed

    Renwick, Andrew G; Molinary, Samuel V

    2010-11-01

    The present review explores the interactions between sweeteners and enteroendocrine cells, and consequences for glucose absorption and insulin release. A combination of in vitro, in situ, molecular biology and clinical studies has formed the basis of our knowledge about the taste receptor proteins in the glucose-sensing enteroendocrine cells and the secretion of incretins by these cells. Low-energy (intense) sweeteners have been used as tools to define the role of intestinal sweet-taste receptors in glucose absorption. Recent studies using animal and human cell lines and knockout mice have shown that low-energy sweeteners can stimulate intestinal enteroendocrine cells to release glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. These studies have given rise to major speculations that the ingestion of food and beverages containing low-energy sweeteners may act via these intestinal mechanisms to increase obesity and the metabolic syndrome due to a loss of equilibrium between taste receptor activation, nutrient assimilation and appetite. However, data from numerous publications on the effects of low-energy sweeteners on appetite, insulin and glucose levels, food intake and body weight have shown that there is no consistent evidence that low-energy sweeteners increase appetite or subsequent food intake, cause insulin release or affect blood pressure in normal subjects. Thus, the data from extensive in vivo studies in human subjects show that low-energy sweeteners do not have any of the adverse effects predicted by in vitro, in situ or knockout studies in animals.

  20. 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.

  1. Somatostatin and the intestinal transport of glucose and other nutrients in the anaesthetised rat.

    PubMed Central

    Daumerie, C; Henquin, J C

    1982-01-01

    The effects of somatostatin on oral glucose tolerance and on intestinal absorption of glucose and other nutrients have been studied in anaesthetised rats. Intravenous somatostatin (0.1-0.6 nmol/min) increased the rate of gastric emptying. After intraduodenal administration of glucose, the rise in peripheral plasma levels of the sugar was delayed, but finally exaggerated by somatostatin, which inhibited the insulin response. Absorption was evaluated by measuring the disappearance of radioactive nutrients from the lumen of a 'tied duodenojejunal loop'. At a luminal concentration of 4 mmol/l of 3-0-methylglucose, neither disappearance of the sugar from the lumen nor its appearance in plasma was affected by somatostatin. Passive transport of 3-0-methylglucose (100 mmol/l) was not significantly modified by somatostatin, although the appearance of the labelled tracer in plasma was delayed. Somatostatin had no significant effect on absorption of galactose (4 mmol/l), sucrose (40 mmol/l), leucine (4 mmol/l) or palmitate (0.1 and 0.4 mmol/l). These results show that somatostatin delays appearance of ingested sugars in peripheral plasma without direct effect on the absorption sites; this delay may result from changes in intestinal motility, enzyme secretion and splanchnic blood flow. PMID:6121743

  2. A kinetic approach to the study of absorption of solutes by isolated perfused small intestine

    PubMed Central

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

    1974-01-01

    1. A new technique has been developed for making serial measurements of water and solute absorption from the lumen of isolated small intestine. 2. The isolated intestine is perfused in a single pass with a segmented flow of slugs of liquid separated by bubbles of oxygen-carbon dioxide mixture. Simultaneous collections are made of effluent from the lumen and of the fluid which is transported across the mucosa. This latter fluid appears to be a fair sample of the tissue fluid. 3. Conditions in the lumen can be changed within less than 5 min. The effects of two or more treatments applied to the same segment of intestine can be determined and the time course of a change in luminal conditions. 4. The rate of appearance of solutes on the serosal side depends on the rate of water absorption, and changes exponentially towards a steady state. The rate constant is a function of tissue fluid volume. 5. In the steady state the concentration of glucose in the tissue fluid is 71 mM when the luminal concentration is 28 mM, and is 45 mM when the luminal concentration is 8·3 mM. 6. For solutes such as glucose for which reflux from tissue fluid to lumen is small relative to flux from lumen to tissue fluid, the time of attainment of a steady state in secretion is usually 50-60 min. 7. For solutes such as sodium for which the reflux is relatively high, the steady state may be reached in 15-20 min. 8. The Km for glucose absorption (14-19 mM) is much lower than is found with unsegmented flow perfusion. 9. These findings emphasize problems in interpreting results from other types of intestinal preparation. 10. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium concentration is reduced abruptly. In contrast the rate of glucose absorption falls suddenly when the luminal glucose concentration is reduced abruptly. This suggests that glucose absorption is not directly dependent on luminal sodium ions. ImagesPlate 1 PMID:4422346

  3. 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

    2015-11-05

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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

  5. 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.

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

    PubMed

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

    2009-12-01

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

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

    PubMed

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

    2013-04-11

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

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

    PubMed Central

    Coon, Steven; Kekuda, Ramesh; Saha, Prosenjit

    2011-01-01

    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

  9. INTESTINAL DIGESTION AND ABSORPTION OF SUGARS AND PEPTIDES.

    DTIC Science & Technology

    The allosteric properties of sucrase were investigated. There is an evident homologous interaction between Na-sites and between substrate-sites... Sucrase , which has no mutarotase activity, liberates glucose in its alpha form. The beta forms of glucose and of some of its derivatives are absorbed...preferentially. Human and rabbit intestinal sucrases were isolated. Antibodies against them were prepared. A new procedure for the measurement of

  10. 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.

  11. Glucose metabolism in the mucosa of the small intestine

    PubMed Central

    Srivastava, L. M.; Hübscher, G.

    1966-01-01

    1. The occurrence of five enzymes of the pentose phosphate pathway in cell-free preparations of the mucosa of rat small intestine is described. These enzymes were found to be localized mainly in the supernatant fraction (6240000g-min.). 2. The properties of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were studied with respect to Km values for substrates and NADP+, pH optima and the effects of p-chloromercuribenzoate and palmitoyl-CoA. Higher total and specific activities of these two dehydrogenases were noted in the proximal half of the small intestine of the rat than in the distal half. 3. The specific activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the mucosa of the small intestine of the rat, cat, rabbit and guinea pig were compared. 4. In the rat the specific activities of ribose 5-phosphate isomerase, transketolase and transaldolase were higher in the supernatant fractions from the intestinal mucosa than in those from the liver. 5. The role of the pentose phosphate pathway is discussed in relation to the metabolism of hexose phosphates in the intestinal mucosa. PMID:4382012

  12. Tiliroside, a glycosidic flavonoid, inhibits carbohydrate digestion and glucose absorption in the gastrointestinal tract.

    PubMed

    Goto, Tsuyoshi; Horita, Mayuka; Nagai, Hiroyuki; Nagatomo, Akifumi; Nishida, Norihisa; Matsuura, Youichi; Nagaoka, Satoshi

    2012-03-01

    Recent studies have reported that tiliroside, a glycosidic flavonoid, possesses anti-diabetic activities. In the present study, we investigated the effects of tiliroside on carbohydrate digestion and absorption in the gastrointestinal tract. This study showed that tiliroside inhibits pancreatic α-amylase (IC₅₀ = 0.28 mM) in vitro. Tiliroside was found as a noncompetitive inhibitor of α-amylase with K(i) values of 84.2 μM. In male ICR mice, the increase in postprandial plasma glucose levels was significantly suppressed in the tiliroside-administered group. Tiliroside treatment also suppressed hyperinsulinemia after starch administration. Tiliroside administration inhibited the increase of plasma glucose levels in an oral glucose tolerance test, but not in an intraperitoneal glucose tolerance test. In human intestinal Caco-2 cells, the addition of tiliroside caused a significant dose-dependent inhibition of glucose uptake. The inhibitory effects of both sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) inhibitors (phlorizin and phloretin, respectively) on glucose uptake were significantly inhibited in the presence of tiliroside, suggesting that tiliroside inhibited glucose uptake mediated by both SGLT1 and GLUT2. These findings indicate that the anti-diabetic effects of tiliroside are at least partially mediated through inhibitory effects on carbohydrate digestion and glucose uptake in the gastrointestinal tract. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. 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.

  14. The effect of ketone bodies and fatty acid on intestinal glucose metabolism during development.

    PubMed

    Kimura, R E; Thulin, G; Warshaw, J B

    1984-07-01

    Glucose oxidation by developing rat intestine changed dramatically during the period of suckling and weaning. After weaning, glucose oxidation to CO2 by intestinal slices increased over 3-fold This was associated with an increase in lactate production from glucose and an increase in the rate of pyruvate decarboxylation. Active pyruvate dehydrogenase in intestine of developing rats also increases in activity at the time of weaning, suggesting that the suppression of glucose oxidation during the suckling period is controlled by pyruvate dehydrogenase. Glucose oxidation to CO2 and pyruvate decarboxylation to CO2 by intestinal slices of postweaned animals was inhibited by exogenous 3-hydroxybutyrate. But exogenous 3-hydroxybutyrate did not inhibit glucose and pyruvate oxidation in intestine of suckling animals which have higher levels of endogenous 3-hydroxybutyrate than intestine of postweaned rats. Palmitate, in contrast, inhibited glucose and pyruvate oxidation by both pre- and postweaned intestine.

  15. Adaptation of intestinal secretomotor function and nutrient absorption in response to diet-induced obesity.

    PubMed

    Hyland, N P; Rybicka, J M; Ho, W; Pittman, Q J; Macnaughton, W K; Sharkey, K A

    2010-06-01

    The gut plays a significant role in the development of obesity, notably through peptide signaling to the brain. However, few studies have investigated intestinal function per se in a rodent model of diet-induced obesity (DIO). Our aim was to investigate intestinal secretomotor function and glucose transport in DIO and diet-resistant (DR) rat jejunum. Male outbred Sprague-Dawley rats were maintained on a medium high fat diet for 9-10 weeks and split into DIO and DR groups based on weight gain. Mucosal-submucosal preparations of the proximal jejunum were mounted in Ussing chambers and voltage-clamped at 0 mV. Glucose (10 mmol L(-1)), 2-deoxy-D-glucose (10 mmol L(-1)), and leptin (10 nmol L(-1)) were added to the luminal side of the tissue and veratridine (30 micromol L(-1)), bethanechol (100 micromol L(-1)), and forskolin (10 micromol L(-1)) were added to the basolateral side of the tissue. Secretomotor responses were significantly decreased in DIO jejunum compared to DR tissues. Glucose-stimulated increases in I(sc) in DR animals, that were sensitive to leptin inhibition, were significantly reduced in DIO rats. Decreased sodium glucose transporter-1 mediated glucose transport was accompanied by a concomitant increase in the expression of jejunal glucose transporter-2. These data suggest that submucosal nerve function is compromised in DIO rats and electrogenic glucose transport is significantly decreased. The latter may represent an adaptive response to limit nutrient absorption in the jejunum from DIO rats. However, the loss of secretomotor control may lead to an altered host defense with a resultant change in intestinal flora contributing to the maintenance of obesity.

  16. Glutamine protects intestinal calcium absorption against oxidative stress and apoptosis.

    PubMed

    Moine, Luciana; Díaz de Barboza, Gabriela; Pérez, Adriana; Benedetto, Mercedes; Tolosa de Talamoni, Nori

    2017-10-01

    The aim of this study was to investigate whether glutamine (GLN) could block the inhibition of the intestinal Ca(2+) absorption caused by menadione (MEN), and elucidate the underlying mechanisms. To do this, one-month old chicks were divided in four groups: 1) controls, 2) MEN treated, 3) GLN treated and 4) GLN treated before or after MEN treatment. Intestinal Ca(2+) absorption as well as protein expression of molecules involved in the transcellular Ca(2+) pathway were determined. Glutathione (GSH) and superoxide anion and activity of enzymes of the antioxidant system were evaluated. Apoptosis was measured by the TUNEL technique, the expression of FAS and FASL and the caspase-3 activity. A previous dose of 0.5gGLN/kg of b.w. was necessary to show its protector effect and a dose of 1g/kg of b.w. could restore the intestinal Ca(2+) absorption after MEN treatment. GLN alone did not modify the protein expression of calbindin D28k and plasma membrane Ca(2+)-ATPase, but blocked the inhibitory effect of the quinone. GLN avoided changes in the intestinal redox state provoked by MEN such as a decrease in the GSH content, and increases in the superoxide anion and in the SOD and CAT activities. GLN abrogated apoptotic effects caused by MEN in intestinal mucosa, as indicated by the reduction of TUNEL (+) cells and the FAS/FASL/caspase-3 pathway. In conclusion, GLN could be an oral nutritional supplement to normalize the redox state and the proliferation/cell death ratio in the small intestine improving the intestinal Ca(2+) absorption altered by oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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

  19. Melibiose, a Nondigestible Disaccharide, Promotes Absorption of Quercetin Glycosides in Rat Small Intestine.

    PubMed

    Tanaka, Seiya; Shinoki, Aki; Hara, Hiroshi

    2016-12-14

    We demonstrated that melibiose, a nondigestible disaccharide composed of galactose and glucose with α-1,6 glycoside linkage, promotes the absorption of water-soluble quercetin glycosides in ligated small intestinal loop of anesthetized rats. Water-soluble quercetin glycoside, a quercetin-3-O-glucoside mixture (Q3GM), includes quercetin-3-O-glucoside (Q3G, 31.9%), mono (21.2%) and di (17.1%), glucose adducts with α-1,4 linkages. After instillation of Q3GM into the intestinal loop with or without melibiose, the plasma concentration of quercetin derivatives in the portal blood was considerably higher in the melibiose group at 60 min. Furthermore, we evaluated the hydrolytic rate of Q3G by the mucosal homogenate of the small intestine with six different disaccharides. Melibiose and isomaltose, which have α-1,6 glycoside linkage, were found to promote Q3G hydrolysis to aglycone. These results suggest that melibiose promotes quercetin glycoside absorption in rats by increasing glycoside hydrolysis in the intestinal lumen and that α-1,6 linkage is involved in this process.

  20. Multiphasic Absorption of Glucose and 3-O-Methyl Glucose by Aged Potato Slices 1

    PubMed Central

    Linask, Juri; Laties, George G.

    1973-01-01

    The isotherm for glucose absorption by aged potato (Solanum tuberosum var. Russet Burbank) discs shows four distinct phases in the concentration ranges 1.0 to 75 μm, 75 μm to 1.5 mm, 1.5 to 15 mm, and 15 to 100 mm, respectively. Each segment of the multiphasic isotherm, when plotted reciprocally by the method of Lineweaver and Burk or of Hofstee, without regard for uptake in earlier phases, indicates absorption rate to be a hyperbolic function of concentration. The observations suggest that glucose uptake is carrier-mediated, and that the transport barrier undergoes a series of all-or-none transformations at critical external concentrations, yielding successive new and higher values for the parameters Km and Vmax 3-O-Methyl glucose, a nonmetabolizable analogue of glucose, shows the same multiphasic absorption isotherm, with Km values essentially similar to those for glucose uptake, and Vmax values somewhat lower than those for glucose absorption. Whereas the first three phases of the absorption isotherm are taken to reflect passage across the plasma membrane, the fourth phase may reflect kinetics of glucose or 3-O-methyl glucose transport to the vacuole. PMID:16658317

  1. The effect of oat β-glucan on in vitro glucose diffusion and glucose transport in rat small intestine.

    PubMed

    Zhang, Yu; Zhang, Hui; Wang, Li; Qian, Haifeng; Qi, Xiguang; Ding, Xiangli; Hu, Bo; Li, Jiajia

    2016-01-30

    Many previous studies have reported the role of oat β-glucan (OBG) in the reduction of postprandial glucose, and hypothesised that OBG may form a protective layer along the intestinal wall, acting as a viscous barrier to decrease glucose transportation. This study examined whether the molecular weight (MW) and concentration of OBG affected the diffusion of glucose in vitro. The effect of OBG on glucose transportation in vitro and sodium-potassium adenosine triphosphatase (Na(+)/K(+)-ATPase) activity in the everted small intestines of normal rats was also examined. In vitro, higher MWs and concentrations of OBG increased the inhibitory effects on glucose diffusion and glucose adsorption. The transport of glucose by glucose transporters and Na(+)/K(+)-ATPase activity in the small intestinal mucosa of rats were significantly lower following the addition of OBG than those in the absence of OBG at the same time-points throughout glucose transportation (P < 0.05). In the OBG-treated group, the Na(+)/K(+)-ATPase activity decreased with increasing OBG MW. However, as the concentration of OBG in the solution increased, the Na(+)/K(+)-ATPase activity in the small intestine increased due to stronger gastrointestinal motility. We also found that higher MWs of OBG had a greater inhibitory effect on intestinal disaccharidase activities in vitro. Oat β-glucan is able to adsorb glucose molecules, inhibit glucose transport, decrease the concentration of available glucose and suppress disaccharidase activities in the small intestine. © 2015 Society of Chemical Industry.

  2. Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40.

    PubMed

    Hidalgo, Jorge; Teuber, Stefanie; Morera, Francisco J; Ojeda, Camila; Flores, Carlos A; Hidalgo, María A; Núñez, Lucía; Villalobos, Carlos; Burgos, Rafael A

    2017-04-05

    Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca(2+) oscillations originated from intracellular Ca(2+) stores and were followed by store-operated Ca(2+) entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management.

  3. Delphinidin Reduces Glucose Uptake in Mice Jejunal Tissue and Human Intestinal Cells Lines through FFA1/GPR40

    PubMed Central

    Hidalgo, Jorge; Teuber, Stefanie; Morera, Francisco J.; Ojeda, Camila; Flores, Carlos A.; Hidalgo, María A.; Núñez, Lucía; Villalobos, Carlos; Burgos, Rafael A.

    2017-01-01

    Anthocyanins are pigments with antihyperglycemic properties, and they are potential candidates for developing functional foods for the therapy or prevention of Diabetes mellitus type 2 (DM2). The mechanism of these beneficial effects of anthocyanins are, however, hard to explain, given their very low bioavailability due to poor intestinal absorption. We propose that free fatty acid receptor 1 (FFA1, also named GPR40), is involved in an inhibitory effect of the anthocyanidin delphinidin over intestinal glucose absorption. We show the direct effects of delphinidin on the intestine using jejunum samples from RF/J mice, and the human intestinal cell lines HT-29, Caco-2, and NCM460. By the use of specific pharmacological antagonists, we determined that delphinidin inhibits glucose absorption in both mouse jejunum and a human enterocytic cell line in a FFA1-dependent manner. Delphinidin also affects the function of sodium-glucose cotransporter 1 (SGLT1). Intracellular signaling after FFA1 activation involved cAMP increase and cytosolic Ca2+ oscillations originated from intracellular Ca2+ stores and were followed by store-operated Ca2+ entry. Taken together, our results suggest a new GPR-40 mediated local mechanism of action for delphinidin over intestinal cells that may in part explain its antidiabetic effect. These findings are promising for the search for new prevention and pharmacological treatment strategies for DM2 management. PMID:28379159

  4. Can lipid nanoparticles improve intestinal absorption?

    PubMed

    Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

    2016-12-30

    Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs.

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

    PubMed Central

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

    1997-01-01

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

  6. 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.

  7. 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.

  8. Intestinal absorption of two dipeptides in Hartnup disease 1

    PubMed Central

    Asatoor, A. M.; Cheng, B.; Edwards, K. D. G.; Lant, A. F.; Matthews, D. M.; Milne, M. D.; Navab, F.; Richards, A. J.

    1970-01-01

    The results of oral tolerance tests of two dipeptides and of their constitutent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide. Results of experiments on absorption and hydrolysis of the two peptides in the rat small intestine are also reported. It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopeptides containing the amino acids affected by the intestinal transport defect of the disease. PMID:5428040

  9. Intestinal absorption of two dipeptides in Hartnup disease.

    PubMed

    Asatoor, A M; Cheng, B; Edwards, K D; Lant, A F; Matthews, D M; Milne, M D; Navab, F; Richards, A J

    1970-05-01

    The results of oral tolerance tests of two dipeptides and of their constitutent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide. Results of experiments on absorption and hydrolysis of the two peptides in the rat small intestine are also reported. It is suggested that whereas normal subjects absorb essential amino acids by a dual mechanism of mucosal uptake of free amino acids and oligopeptides, nutrition in Hartnup disease is largely dependent on uptake of oligopeptides containing the amino acids affected by the intestinal transport defect of the disease.

  10. Studies on Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Skoryna, Stanley C.; Paul, T. M.; Edward, Deirdre Waldron

    1964-01-01

    A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting the calcium to be available to the body. Studies were carried out in vivo by injection of Sr89 and Ca45 in the presence of inert carrier into ligated intestinal segments in rats, and the amount of absorption was measured by standard monitoring techniques. The pattern of absorption of both ions is very similar but the rate of absorption is different. It was found that the polyelectrolyte, sodium alginate, obtained from brown algae (Phaeophyceae), injected simultaneously with radiostrontium effectively reduces the absortion of Sr89 from all segments of the intestine by as much as 50-80% of the control values. No significant reduction in absorption of Ca45 was observed in equivalent concentrations. The reduction in blood levels of Sr89 and in bone uptake corresponded to the absorption pattern. The difference in the effect on strontium and calcium absorption may be due to differences in the binding capacity of sodium alginate from the two metal ions under the conditions present in vivo. PMID:14180534

  11. Inhibition of small-intestinal sugar absorption mediated by sodium orthovanadate Na3VO4 in rats and its mechanisms

    PubMed Central

    Ai, Jing; Du, Jie; Wang, Ning; Du, Zhi-Min; Yang, Bao-Feng

    2004-01-01

    AIM: To investigate the inhibitory effects of sodium orthovanadate on small-intestinal glucose and maltose absorption in rats and its mechanism. METHODS: Normal Wistar rats were lavaged with sodium orthovanadate (16 mg/kg, 4 mg/kg and 1 mg/kg) for 6 d. Blood glucose values were measured after fasting and 0.5, 1, 1.5 and 2 h after glucose and maltose feeding with oxidation-enzyme method. α-glucosidase was abstracted from the upper small intestine, and its activity was examined. mRNA expression of α-glucosidase and glucose-transporter 2 (GLUT2) in epithelial cells of the small intestine was observed by in situ hybridization. RESULTS: Sodium orthovanadate could delay the increase of plasma glucose concentration after glucose and maltose loading, area under curve (AUC) in these groups was lower than that in control group. Sodium orthovanadate at dosages of 10 μmol/L, 100 μmol/L and 1000 μmol/L could suppress the activity of α-glucosidase in the small intestine of normal rats, with an inhibition rate of 68.18%, 87.22% and 91.91%, respectively. Sodium orthovanadate reduced mRNA expression of α-glucosidase and GLUT2 in epithelial cells of small intestine. CONCLUSION: Sodium orthovanadate can reduce and delay the absorption of glucose and maltose. The mechanism may be that it can inhibit the activity and mRNA expression of α-glucosidase, as well as mRNA expression of GLUT2 in small intestine. PMID:15534916

  12. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Inhibitory effect of IL-1β on galactose intestinal absorption in rabbits.

    PubMed

    Viñuales, Carmen; Gascón, Sonia; Barranquero, Cristina; Osada, Jesús; Rodríguez-Yoldi, Ma Jesús

    2012-01-01

    Recent studies from our laboratory have shown that nitric oxide is involved in the IL-1β-induced inhibition of D-fructose intestinal transport in rabbits. The aim of this work was to further the studies of IL-1β effect on D-galactose absorption in a septic state induced by intravenous administration of this cytokine. Galactose intestinal absorption was assessed employing three techniques: sugar uptake in jejunum everted rings, transepithelial flux in Ussing-type chambers and uptake assays in brush border membrane vesicles. The level of the Na(+)/D-glucose cotransporter (SGLT1) expression was analyzed by Western blot. In sepsis condition the body temperature was increased and studies on cellular intestinal integrity have not shown modifications in the brush border membrane. However, D-galactose absorption across mucosa of jejunum was diminished in IL-1β treated rabbits. The levels of SGLT-1 were no significantly different in both animal groups (control and IL-1β treated), indicating that the cytokine could induce a reduction in the SGLT-1 functionality. The inhibition was significantly reversed by the activation of several PKC, PKA, MAPKs and nuclear factor (NF)-ĸB inhibitors administered 15 min before the IL-1β. The inhibitory effect of IL-1β on D-galactose absorption across mucosal side of enterocyte could be mediated by the activation of several kinases and nuclear factor (NF)-ĸB. Copyright © 2012 S. Karger AG, Basel.

  14. Sensitivity analysis of near-infrared glucose absorption signals: toward noninvasive blood glucose sensing

    NASA Astrophysics Data System (ADS)

    Saptari, Vidi A.; Youcef-Toumi, Kamal

    2000-11-01

    Noninvasive blood glucose monitoring is a long pursued goal in clinical diagnostic. Among several other optical methods, near infrared absorption spectroscopy is the most promising one for the noninvasive application to date. However, realization has not been achieved. A major obstacle is the low signal-to-noise ration pertinent to physiological blood glucose measurement using the near infrared absorption technique. Sensitivity analysis of aqueous glucose absorption signals was performed in the combination band region and in the first-overtone region. The analysis involved quantification of both glucose absorption signal and the corresponding spectral noise within a particular wavelength region. Glucose absorption band at 4430cm-1 (2257nm) in the combination band region was found to give an order of magnitude higher signal-to-noise ratio than the strongest band in the first-overtone region. A Fourier- filtering algorithm was applied to the raw absorbance data to remove some of the unwanted spectral variations. With simple peak-to-peak analysis to the Fourier-filtered absorbance data, repeatability of less than +/-0.5mmol/L was achieved. In addition, effects of temperature variations on the absorption spectra were studied. The effects of sample temperature were compensated with the application of the Fourier filter.

  15. The multicopper ferroxidase hephaestin enhances intestinal iron absorption in mice.

    PubMed

    Fuqua, Brie K; Lu, Yan; Darshan, Deepak; Frazer, David M; Wilkins, Sarah J; Wolkow, Natalie; Bell, Austin G; Hsu, JoAnn; Yu, Catherine C; Chen, Huijun; Dunaief, Joshua L; Anderson, Gregory J; Vulpe, Chris D

    2014-01-01

    Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex-linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia mice still retain some hephaestin ferroxidase activity. They survive, breed, and their anemia improves with age. To gain a better understanding of the role of hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout mouse models with whole body or intestine-specific (Villin promoter) ablation of hephaestin. Both types of mice were viable, indicating that hephaestin is not essential and that other mechanisms, multicopper ferroxidase-dependent or not, must compensate for hephaestin deficiency. The knockout strains, however, both developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition. Consistent with this, the knockout mice accumulated iron in duodenal enterocytes and had reduced intestinal iron absorption. In addition, the similarities of the phenotypes of the whole body and intestine-specific hephaestin knockout mice clarify the important role of hephaestin specifically in intestinal enterocytes in maintaining whole body iron homeostasis. These mouse models will serve as valuable tools to study the role of hephaestin and associated proteins in iron transport in the small intestine and other tissues.

  16. The Multicopper Ferroxidase Hephaestin Enhances Intestinal Iron Absorption in Mice

    PubMed Central

    Fuqua, Brie K.; Lu, Yan; Darshan, Deepak; Frazer, David M.; Wilkins, Sarah J.; Wolkow, Natalie; Bell, Austin G.; Hsu, JoAnn; Yu, Catherine C.; Chen, Huijun; Dunaief, Joshua L.; Anderson, Gregory J.; Vulpe, Chris D.

    2014-01-01

    Hephaestin is a vertebrate multicopper ferroxidase important for the transfer of dietary iron from intestinal cells to the blood. Hephaestin is mutated in the sex-linked anemia mouse, resulting in iron deficiency. However, sex-linked anemia mice still retain some hephaestin ferroxidase activity. They survive, breed, and their anemia improves with age. To gain a better understanding of the role of hephaestin in iron homeostasis, we used the Cre-lox system to generate knockout mouse models with whole body or intestine-specific (Villin promoter) ablation of hephaestin. Both types of mice were viable, indicating that hephaestin is not essential and that other mechanisms, multicopper ferroxidase-dependent or not, must compensate for hephaestin deficiency. The knockout strains, however, both developed a microcytic, hypochromic anemia, suggesting severe iron deficiency and confirming that hephaestin plays an important role in body iron acquisition. Consistent with this, the knockout mice accumulated iron in duodenal enterocytes and had reduced intestinal iron absorption. In addition, the similarities of the phenotypes of the whole body and intestine-specific hephaestin knockout mice clarify the important role of hephaestin specifically in intestinal enterocytes in maintaining whole body iron homeostasis. These mouse models will serve as valuable tools to study the role of hephaestin and associated proteins in iron transport in the small intestine and other tissues. PMID:24896847

  17. Altered intestinal absorption of L-thyroxine caused by coffee.

    PubMed

    Benvenga, Salvatore; Bartolone, Luigi; Pappalardo, Maria Angela; Russo, Antonia; Lapa, Daniela; Giorgianni, Grazia; Saraceno, Giovanna; Trimarchi, Francesco

    2008-03-01

    To report eight case histories, and in vivo and in vitro studies showing coffee's potential to impair thyroxine (T4) intestinal absorption. Of eight women with inappropriately high or nonsuppressed thyroid-stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six consented to the evaluation of their T4 intestinal absorption. This in vivo test was also administered to nine volunteers. In three separate tests, two 100 microg T4 tablets were swallowed with coffee, water, or water followed, 60 minutes later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two patients and two volunteers also agreed on having tested the intestinal absorption of T4 swallowed with solubilized dietary fibers. In the in vitro studies, classical recovery tests on known concentrations of T4 were performed in the presence of saline, coffee, or known T4 sequestrants (dietary fibers, aluminium hydroxide, and sucralfate). For the in vivo test, average and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were determined. In patients and volunteers, the four outcome measures were similar in the water and water + coffee tests. In patients and volunteers, compared to water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior interferer. In the in vitro studies, coffee was weaker than known T4 sequestrants. Coffee should be added to the list of interferers of T4 intestinal absorption, and T4 to the list of compounds whose absorption is affected by coffee.

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

    PubMed

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

    2013-11-15

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

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

    PubMed Central

    Schwartz, John H.; Rajendran, Vazhaikkurichi M.; Jepeal, Lisa; Singh, Satish K.

    2013-01-01

    Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes. The present study investigated the effect of GIP on proton-peptide cotransporter-1 (PepT1) that mediates di- and tripeptide absorption as well as peptidomimetic drugs. Immunohistochemistry studies localized both GIP receptor (GIPR) and PepT1 proteins on the basolateral and apical membranes of normal mouse jejunum, respectively. Anti-GIPR antibody detected 50-, 55-, 65-, and 70-kDa proteins, whereas anti-PepT1 detected a 70-kDa proteins in mucosal homogenates of mouse jejunum. RT-PCR analyses established the expression of GIPR- and PepT1-specific mRNA in mucosal cells of mouse jejunum. Absorption of Gly-Sar (a nondigestible dipeptide) measured under voltage-clamp conditions revealed that the imposed mucosal H+ gradient-enhanced Gly-Sar absorption as an evidence for the presence of PepT1-mediated H+:Gly-Sar cotransport on the apical membranes of mouse jejunum. H+:Gly-Sar absorption was completely inhibited by cephalexin (a competitive inhibitor of PepT1) and was activated by GIP. The GIP-activated Gly-Sar absorption was completely inhibited by RP-cAMP (a cAMP antagonist). In contrast to GIP, the ileal L cell secreting glucagon-like peptide-1 (GLP-1) did not affect the H+:Gly-Sar absorption in mouse jejunum. We conclude from these observations that GIP, but not GLP-1, directly activates PepT1 activity by a cAMP-dependent signaling pathway in jejunum. PMID:24072682

  20. 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

  1. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells[S

    PubMed Central

    Awada, Manar; Soulage, Christophe O.; Meynier, Anne; Debard, Cyrille; Plaisancié, Pascale; Benoit, Bérengère; Picard, Grégory; Loizon, Emmanuelle; Chauvin, Marie-Agnès; Estienne, Monique; Peretti, Noël; Guichardant, Michel; Lagarde, Michel; Genot, Claude; Michalski, Marie-Caroline

    2012-01-01

    Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to −19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine. PMID:22865918

  2. Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells.

    PubMed

    Awada, Manar; Soulage, Christophe O; Meynier, Anne; Debard, Cyrille; Plaisancié, Pascale; Benoit, Bérengère; Picard, Grégory; Loizon, Emmanuelle; Chauvin, Marie-Agnès; Estienne, Monique; Peretti, Noël; Guichardant, Michel; Lagarde, Michel; Genot, Claude; Michalski, Marie-Caroline

    2012-10-01

    Dietary intake of long-chain n-3 PUFA is now widely advised for public health and in medical practice. However, PUFA are highly prone to oxidation, producing potentially deleterious 4-hydroxy-2-alkenals. Even so, the impact of consuming oxidized n-3 PUFA on metabolic oxidative stress and inflammation is poorly described. We therefore studied such effects and hypothesized the involvement of the intestinal absorption of 4-hydroxy-2-hexenal (4-HHE), an oxidized n-3 PUFA end-product. In vivo, four groups of mice were fed for 8 weeks high-fat diets containing moderately oxidized or unoxidized n-3 PUFA. Other mice were orally administered 4-HHE and euthanized postprandially versus baseline mice. In vitro, human intestinal Caco-2/TC7 cells were incubated with 4-hydroxy-2-alkenals. Oxidized diets increased 4-HHE plasma levels in mice (up to 5-fold, P < 0.01) compared with unoxidized diets. Oxidized diets enhanced plasma inflammatory markers and activation of nuclear factor kappaB (NF-κB) in the small intestine along with decreasing Paneth cell number (up to -19% in the duodenum). Both in vivo and in vitro, intestinal absorption of 4-HHE was associated with formation of 4-HHE-protein adducts and increased expression of glutathione peroxidase 2 (GPx2) and glucose-regulated protein 78 (GRP78). Consumption of oxidized n-3 PUFA results in 4-HHE accumulation in blood after its intestinal absorption and triggers oxidative stress and inflammation in the upper intestine.

  3. Oral IGF-I enhances nutrient and electrolyte absorption in neonatal piglet intestine.

    PubMed

    Alexander, A N; Carey, H V

    1999-09-01

    The effect of orally administered insulin-like growth factor-I (IGF-I) on small intestinal structure and function was studied in 5-day-old colostrum-deprived piglets. Human recombinant IGF-I (3.5 mg. kg(-1). day(-1)) or control vehicle was given orogastrically for 4 days. Body weights, jejunal and ileal mucosa wet and dry weights, and serum IGF-I levels were similar in the two groups. Small intestinal villus height and crypt depth and jejunal enterocyte microvillar dimensions were also similar between groups. Oral IGF-I produced higher rates of jejunal ion transport because of increased basal Na+ absorption. Short-circuit current responses to mucosal addition of D-glucose and L-alanine and net transepithelial absorption of 3-O-methylglucose were increased by IGF-I. Carrier-mediated uptake of D-glucose per milligram in everted jejunal sleeves was greater in IGF-I-treated piglets because of a significantly greater maximal rate of uptake. We conclude that rates of net Na+ and Na+-dependent nutrient absorption are enhanced in piglets treated with oral IGF-I, and this effect is independent of changes in mucosal mass or surface area.

  4. Glucose Absorption by the Bacillary Band of Trichuris muris.

    PubMed

    Hansen, Tina V A; Hansen, Michael; Nejsum, Peter; Mejer, Helena; Denwood, Matthew; Thamsborg, Stig M

    2016-09-01

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

  5. Glucose Absorption by the Bacillary Band of Trichuris muris

    PubMed Central

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

    2016-01-01

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

  6. 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. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

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

    PubMed

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

    2012-02-20

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

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

    PubMed Central

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

    2015-01-01

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

  9. Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice.

    PubMed

    Dimova, Lidiya G; de Boer, Jan Freark; Plantinga, Josee; Plösch, Torsten; Hoekstra, Menno; Verkade, Henkjan J; Tietge, Uwe J F

    2017-08-01

    In nematodes, the intestine senses and integrates early life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from maternal milk and investigate the consequences of decreased milk cholesterol availability, early in life, on the metabolism of cholesterol in adult mice. We blocked intestinal absorption of cholesterol in milk fed to newborn mice by supplementing the food of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted into milk. Ezetimibe interacts with the intestinal cholesterol absorption transporter NPC1l1 to block cholesterol uptake into enterocytes. Characterization of these offspring at 24 weeks of age showed a 27% decrease in cholesterol absorption (P < .001) and reduced levels of Npc1l1 messenger RNA and protein, but not other cholesterol transporters, in the proximal small intestine. We observed increased histone H3K9me3 methylation at positions -423 to -607 of the proximal Npc1l1 promoter in small intestine tissues from 24-week-old offspring fed ezetimibe during lactation, compared with controls. These findings show that the early postnatal mammalian intestine functions as an environmental sensor of nutritional conditions, responding to conditions such as low cholesterol levels by epigenetic modifications of genes. Further studies are needed to determine how decreased sterol absorption for a defined period might activate epigenetic regulators; the findings of our study might have implications for human infant nutrition and understanding and preventing cardiometabolic disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Intestinal sucrase inhibitors and bile acid absorption in the rat

    SciTech Connect

    Walsh, C.T.; Harnett, K.M.

    1986-03-01

    Studies were carried out to determine if bile acid absorption is perturbed by the intestinal sucrase inhibitors, Acarbose and BAY m 1099 (1,5-dideoxy-1.5((2-hydroxy-ethyl) imino-)-D-glucitol). The intestinal absorption of taurocholic acid (TA) in male Wistar rats, anesthetized with pentobarbital (50mg/ig, i.p.), was assessed from its excretion rate in bile. In acute studies, 15 cm of distal ileum was perfused in vivo for 70 min with /sup 14/C-TA (0.1 mM, 5 ..mu.. Ci/mmol) in 0.154 M NaCl, 0.01 M phosphate (pH 6.8) and in some studies 20 mM sucrose. From 70-140 min the perfusate was unchanged or contained Acarbose (150, 1500 ..mu..g/ml) or BAY m 1099 (10, 25 ..mu..g/ ml). Neither drug without sucrose altered TA biliary excretion. With sucrose, BAY m 1099 (10 and 25 ..mu.. g/ml) reduced TA excretion by 11 and 22%; no greater effect occurred with 60..mu..g/ml. In subchronic studies rats were fed Acarbose (40 mg/100 g diet) or BAY m 1099 (10, 20, 40 mg/100 g diet) in AIN-76A (50% cornstarch, 15% sucrose) and after 8 wk /sup 14/C-TA (10 mg/kg, 0.08 ..mu..Ci/mg, 3 mg/ml 0.9% NaCl) was injected into the proximal small intestine. Neither drug affected the biliary excretion of TA, measured every 20 min for 4-5 hr. These studies indicate that neither acute nor subchronic regimes of Acarbose or BAY m 1099 affect the intestinal absorption of TA. A possible effect in the presence of sucrose is being explored.

  12. Increased luminal mucin does not disturb glucose or ovalbumin absorption in rats fed insoluble dietary fiber.

    PubMed

    Morita, Tatsuya; Tanabe, Hiroki; Ito, Hiroyuki; Yuto, Shunsuke; Matsubara, Takeshi; Matsuda, Tsukasa; Sugiyama, Kimio; Kiriyama, Shuhachi

    2006-10-01

    We tested whether increased mucin secretion due to ingestion of insoluble dietary fiber (IDF) affects small intestinal nutrient absorption in rats. Polystyrene foam (PSF) with a true expansion ratio of 54.9 was used as a model for IDF with high bulk-forming properties. In Expt. 1, rats were fed a control diet or diet containing 50 g PSF/kg for 1, 3, 5, or 7 d. Small intestinal mucin fractions were isolated, and O-linked oligosaccharide chains were measured. The luminal mucin content reached a maximum within 5 d after PSF ingestion. In Expt. 2, rats were fed a control diet or diet containing 50 g PSF/kg for 7 d, and then all rats were switched to the control diet for 1, 3, or 5 d. The increased capacity for luminal mucin secretion disappeared within 5 d after ceasing PSF ingestion. In Expt. 3, rats were fed a control diet or diet containing 70 g PSF/kg for 7 d. Glucose (1g/kg) was administered orally after 12 h of food deprivation. The blood glucose concentrations did not differ between the groups. In Expt. 4, rats were fed a control diet or diet containing 90 g PSF/kg for 14 d. At d 7, portal cannulae were installed. A mixed solution of glucose (1g/kg) and ovalbumin (OVA, 250 mg/kg) was orally administered after 12 h of food deprivation, and responses of portal glucose and OVA concentrations were monitored for 120 min. Although luminal mucin contents were almost doubled in the 9% PSF group compared with the control group, neither portal glucose nor OVA concentration differed at any time point. The results suggest that the short-term ingestion of IDF significantly increases the luminal mucin content, but that this does not disturb nutrient absorption.

  13. Intestinal absorption and renal reabsorption of calcium throughout postnatal development

    PubMed Central

    Beggs, Megan R

    2017-01-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  14. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    PubMed

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  15. Analysis of sequential events in intestinal absorption of folylpolyglutamate

    SciTech Connect

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

    1988-09-01

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

  16. Simple test of intestinal calcium absorption measured by stable strontium.

    PubMed Central

    Milsom, S; Ibbertson, K; Hannan, S; Shaw, D; Pybus, J

    1987-01-01

    A clinical test of intestinal calcium absorption has been developed using non-radioactive stable strontium as a calcium tracer. In nine elderly subjects there was a close correlation between the fractional absorption of strontium and radioactive calcium (45Ca) during a five hour period after the simultaneous oral administration of the two tracers. Comparable precision was achieved with each tracer in six subjects in whom the test was repeated after two weeks. The effect of food on strontium absorption was examined in a further 33 normal subjects (age 21-60 years), and the administration of the strontium with a standard breakfast was shown to reduce the variance at individual time points. A simplified test in which serum strontium concentration was measured four hours after the oral dose given with a standard breakfast was adopted as the routine procedure. The normal range (mean (2 SD], established over 97 tests in 53 patients, was 7.0-18.0% of the dose in the extracellular fluid. A further 30 patients with possible disorders of calcium absorption (10 with primary hyperparathyroidism and 20 with coeliac disease) were studied by this standard test. In both groups of patients the mean four hour strontium values were significantly different from normal. This standard strontium absorption test allows assessment of calcium absorption with sufficient sensitivity and precision to have a wide application in clinical practice. PMID:3115389

  17. Variability of bioavailability and intestinal absorption mechanisms of metoprolol.

    PubMed

    Fukao, Miki; Ishida, Kazuya; Horie, Asuka; Taguchi, Masato; Nozawa, Takashi; Inoue, Hiroshi; Hashimoto, Yukiya

    2014-01-01

    We previously reported that aging and/or cytochrome P450 2D6 polymorphism are responsible for the interindividual variability in the systemic clearance (CL) and bioavailability (F) of metoprolol. The aim of the present study was to evaluate the residual variability of F of metoprolol in routinely treated Japanese patients and to investigate the intestinal absorption mechanism of the drug using human intestinal epithelial LS180 cells. We first re-analyzed the blood concentration data for metoprolol in 34 Japanese patients using a nonlinear mixed effects model. The oral clearance (CL/F) of metoprolol was positively correlated with the apparent volume of distribution (V/F), suggesting the residual variability of F. The uptake of metoprolol into LS180 cells was significantly decreased by the acidification of extracellular medium pH, and was dependent on temperature and intracellular pH. Furthermore, the cellular uptake of metoprolol was saturable, and was significantly decreased in the presence of hydrophobic cationic drugs such as diphenhydramine, procainamide, bisoprolol, and quinidine. These findings indicate that residual variability of F is one of the causes of the interindividual pharmacokinetic variability of metoprolol, and that the interindividual variability of not only presystemic first-pass metabolism, but also intestinal absorption, may be responsible for the variable F of the drug.

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

    PubMed

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

    2014-12-29

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

  19. Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs

    PubMed Central

    Gurunath, S.; Nanjwade, Baswaraj K.; Patila, P.A.

    2013-01-01

    Objective Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for its incomplete intestinal absorption. Methods In this study, we investigated to enhance the absorption of CAN by improving its solubility and inhibiting intestinal P-gp activity. A phase solubility method was used to evaluate the aqueous solubility of CAN in PVP K30 (0.2–2%). Gibbs free energy (ΔGtro) values were all negative. Solubility was enhanced by the freeze drying technique. The in vitro dissolution was evaluated using the USP paddle method. The interaction between drug and carrier was evaluated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption studies were performed using the everted gut sac model from rat jejunum. The drug analysis was performed by HPLC. Results FTIR spectra revealed no interaction between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form, which explains the cumulative release of drug from its prepared systems. We noticed an enhancement of CAN absorption by improving its solubility and inhibiting the P-gp activity. The significant results (p < 0.05) were obtained for freeze dried solid dispersions in the presence of P-gp inhibitor than without naringin (15 mg/kg) with an absorption enhancement of 8-fold. Conclusion Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it could be employed as an excipient in the form of solid dispersions to increase CAN intestinal absorption and its oral bioavailability. PMID:25067902

  20. Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

    PubMed

    Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2011-01-05

    Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine.

  1. Methylated flavonoids have greatly improved intestinal absorption and metabolic stability.

    PubMed

    Wen, Xia; Walle, Thomas

    2006-10-01

    To better understand the relationship between the chemical structure and biological fate of dietary polyphenols, the hepatic metabolic stability and intestinal absorption of methylated polyphenols, in comparison with unmethylated polyphenols, were investigated in pooled human liver S9 fraction and human colon adenocarcinoma (Caco-2) cells. Consistent with previous in vivo studies, the two well known unmethylated polyphenols resveratrol (3,5,4'-trihydroxystilbene) and quercetin (3,5,7,3',4'-pentahydroxyflavone) were rapidly eliminated by the S9 fraction in the presence of the appropriate cofactors for conjugation and oxidation. In contrast, the methylated flavones, i.e., 7-methoxyflavone, 7,4'-dimethoxyflavone, 5,7-dimethoxyflavone, and 5,7,4'-trimethoxyflavone, were relatively stable, indicating high resistance to hepatic metabolism. The corresponding unmethylated flavones, i.e., 7-hydroxyflavone, 7,4'-dihydroxyflavone, chrysin (5,7-dihydroxyflavone), and apigenin (5,7,4'-trihydroxyflavone), were rapidly eliminated because of extensive glucuronidation and/or sulfation just as resveratrol and quercetin were. The rate of intestinal absorption was evaluated using Caco-2 cells grown in porous inserts. The methylated flavones showed approximately 5- to 8-fold higher apparent permeability (P(app), 22.6-27.6 x 10(-6) cm s(-1)) of apical to basolateral flux than the unmethylated flavones (P(app), 3.0-7.8 x 10(-6) cm s(-1)). The lower P(app) values for the unmethylated flavones correlated with their extensive metabolism in the Caco-2 cells. Thus, combined use of the hepatic S9 fraction and Caco-2 cells will be useful for predicting the oral bioavailability of dietary polyphenols. The higher hepatic metabolic stability and intestinal absorption of the methylated polyphenols make them more favorable than the unmethylated polyphenols to be developed as potential cancer chemopreventive agents.

  2. Regulation of Glucose Uptake and Enteroendocrine Function by the Intestinal Epithelial Insulin Receptor.

    PubMed

    Ussar, Siegfried; Haering, Max-Felix; Fujisaka, Shiho; Lutter, Dominik; Lee, Kevin Y; Li, Ning; Gerber, Georg K; Bry, Lynn; Kahn, C Ronald

    2017-04-01

    Insulin receptors (IRs) and IGF-I receptors (IGF-IR) are major regulators of metabolism and cell growth throughout the body; however, their roles in the intestine remain controversial. Here we show that genetic ablation of the IR or IGF-IR in intestinal epithelial cells of mice does not impair intestinal growth or development or the composition of the gut microbiome. However, the loss of IRs alters intestinal epithelial gene expression, especially in pathways related to glucose uptake and metabolism. More importantly, the loss of IRs reduces intestinal glucose uptake. As a result, mice lacking the IR in intestinal epithelium retain normal glucose tolerance during aging compared with controls, which show an age-dependent decline in glucose tolerance. Loss of the IR also results in a reduction of glucose-dependent insulinotropic polypeptide (GIP) expression from enteroendocrine K-cells and decreased GIP release in vivo after glucose ingestion but has no effect on glucagon-like peptide 1 expression or secretion. Thus, the IR in the intestinal epithelium plays important roles in intestinal gene expression, glucose uptake, and GIP production, which may contribute to pathophysiological changes in individuals with diabetes, metabolic syndrome, and other insulin-resistant states. © 2017 by the American Diabetes Association.

  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. 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.

  5. 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.

  6. Effect of Diet upon Intestinal Disaccharidases and Disaccharide Absorption*

    PubMed Central

    Deren, J. J.; Broitman, S. A.; Zamcheck, N.

    1967-01-01

    The administration of a carbohydrate-containing diet for 24 hours to rats previously fasted for 3 days led to a twofold increase in total intestinal sucrase and sucrase specific activity. The specific activity of maltase was similarly increased, but lactase activity was unaffected. The sucrose-containing diet led to a greater increase in sucrase than maltase activity, whereas the converse was true of the maltose-containing diet. A carbohydrate-free isocaloric diet led to a slight increase in the total intestinal sucrase, but sucrase specific activity was unchanged. Assay of sucrase activity of mixed homogenates from casein-fed and sucrose-fed rats or fasted and sucrose-fed animals yielded activities that were additive. The Michaelis constant (Km) of the enzyme hydrolyzing sucrose was similar in the fasted, casein-fed, and sucrose-fed rats. The maximal velocity (Vmax) was twice greater in sucrose-fed as compared to casein-fed or fasted rats, suggesting an increased quantity of enzyme subsequent to sucrose feeding. Adrenalectomized rats maintained on 1.0% salt intake had sucrase and maltase levels comparable to those of controls. Steroid administration did not significantly increase their activities. The response to sucrose feeding was similar in both control and adrenalectomized rats, indicative of the absence of steroidal control on sucrase and maltase activity in the adult animal. Studies using intestinal ring preparations indicated that sucrose hydrolysis by the intact cells proceeded more rapidly when animals were fed sucrose. Additional corroboration of the physiologic significance of the increased enzyme levels in homogenates was afforded by intestinal perfusion studies. Sucrose hydrolysis increased twofold and fructose absorption fourfold in animals fed sucrose when compared to either fasted or casein-fed rats. PMID:6018758

  7. Establishment of novel prediction system of intestinal absorption in humans using human intestinal tissues.

    PubMed

    Miyake, Masateru; Toguchi, Hajime; Nishibayashi, Toru; Higaki, Kazutaka; Sugita, Akira; Koganei, Kazutaka; Kamada, Nobuhiko; Kitazume, Mina T; Hisamatsu, Tadakazu; Sato, Toshiro; Okamoto, Susumu; Kanai, Takanori; Hibi, Toshifumi

    2013-08-01

    The objective of this study was to establish a novel prediction system of drug absorption in humans by utilizing human intestinal tissues. Based on the transport index (TI), a newly defined parameter, calculated by taking account of the change in drug concentrations because of precipitation on the apical side and the amounts accumulated in the tissue and transported to the basal side, the absorbability of drugs in rank order as well as the fraction of dose absorbed (Fa) in humans were estimated. Human intestinal tissues taken from ulcerative colitis or Crohn's disease patients were mounted in a mini-Ussing chamber and transport studies were performed to evaluate the permeation of drugs, including FD-4, a very low permeable marker, atenolol, a low permeable marker, and metoprolol, a high permeable marker. Although apparent permeability coefficients calculated by the conventional equation did not reflect human Fa values for FD-4, atenolol, and metoprolol, TI values were well correlated with Fa values, which are described by 100 · [1 - e (- f · (TI - α)) ]. Based on this equation, Fa values in humans for other test drugs were predicted successfully, indicating that our new system utilizing human intestinal tissues would be valuable for predicting oral drug absorption in humans.

  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. Targeted intestinal delivery of supersaturated itraconazole for improved oral absorption.

    PubMed

    Miller, Dave A; DiNunzio, James C; Yang, Wei; McGinity, James W; Williams, Robert O

    2008-06-01

    To investigate the use of Carbopol 974P as a stabilizing agent for supersaturated levels of itraconazole (ITZ) in neutral pH aqueous media and the resultant effects on oral absorption of ITZ. Carbopol 974P was incorporated into an EUDRAGIT L 100-55 carrier matrix at concentrations of 20% and 40% based on polymer weight with the aim of prolonging supersaturated ITZ release from the enteric matrix. Amorphous solid dispersions of ITZ in EUDRAGIT L 100-55 containing either 20% or 40% Carbopol 974P were produced by hot-melt extrusion (HME). Solid state analysis of these compositions was performed using differential scanning calorimetry and qualitative energy dispersive X-ray spectroscopy. Dissolution analysis was conducted using a pH change method. Oral absorption of ITZ was evaluated in male Sprague-Dawley rats. Solid state analysis demonstrated that the extruded compositions were entirely amorphous and homogenous with respect to drug distribution in the polymer matrix. Dissolution analysis revealed that the addition of Carbopol 974P to the EUDRAGIT L 100-55 carrier system functioned to prolong the release of supersaturated levels of ITZ from the EUDRAGIT L 100-55 matrix following an acidic-to-neutral pH transition. In vivo evaluation of ITZ absorption revealed that the addition of Carbopol 974P substantially reduced the absorption variability seen with the EUDRAGIT L 100-55 carrier system. In addition, the 20% Carbopol 974P formulation exhibited a five-fold improvement in absorption over our initially reported ITZ particulate dispersion compositions that limited supersaturation of ITZ primarily to the stomach. The results of this study strongly suggest that substantial improvements in oral antifungal therapy with ITZ can be achieved via intestinal targeting and polymeric stabilization of supersaturation.

  10. 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.

  11. Studies on Inhibition of the Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Tanaka, Y.; Inoue, S.; Skoryna, S. C.

    1970-01-01

    The inhibitory action of alginate on intestinal absorption of radioactive strontium was investigated in order to correlate the biological activity with the chemical composition. Alginate from Laminaria hyperborea was partially hydrolyzed with oxalic acid and the degradation products were fractionated into polymannuronic and polyguluronic acid. The activity of these products was assessed biologically in rats and morphologically by electron microscopy. Sodium polymannuronate was found to be less effective than sodium polyguluronate in preventing absorption of radiostrontium. The inhibition of absorption of radio-calcium was low and not affected by hydrolysis or fractionation. When dried from dilute aqueous solutions, the polymannuronate retained the original helical structure of alginate, while the polyguluronate showed a strong tendency to coagulate, forming granules. The variation in the biological activity was attributed to the morphological differences between these alginic acid components and it is suggested that the degree of uncoiling of the polyguluronate chain in water is greater than that of the polymannuronate chain, thus making the carboxylate ions more accessible to strontium. ImagesFIG. 2FIG. 3 PMID:5469618

  12. 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.

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

    PubMed

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

    2016-01-01

    A study was undertaken to evaluate dietary glutamine supplementation effects on gilthead sea bream performance, intestinal nutrient absorption capacity, hepatic and intestinal glutamine metabolism and oxidative status. For that purpose gilthead sea bream juveniles (mean weight 13.0g) were fed four isolipidic (18% lipid) and isonitrogenous (43% protein) diets supplemented with 0, 0.5, 1 and 2% glutamine for 6weeks. Fish performance, body composition and intestinal nutrient absorption capacity were not affected by dietary glutamine levels. Hepatic and intestinal glutaminase (GlNase), glutamine synthetase (GSase), alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities were also unaffected by dietary glutamine supplementation. In the intestine GlNase activity was higher and GSase/GlNase ratio was two-fold lower than in the liver, suggesting a higher use of glutamine for energy production by the intestine than by the liver. The liver showed higher catalase and glucose-6-phosphate dehydrogenase activities, while the intestine presented higher glutathione peroxidase and glutathione reductase activities and oxidised glutathione content, which seems to reveal a higher glutathione dependency of the intestinal antioxidant response. Total and reduced glutathione contents in liver and intestine and superoxide dismutase activity in the intestine were enhanced by dietary glutamine, though lipid peroxidation values were not affected. Overall, differences between liver and intestine glutamine metabolism and antioxidant response were identified and the potential of dietary glutamine supplementation to gilthead sea bream's antioxidant response was elucidated. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2014-05-15

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

  15. 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

  16. [Intestinal absorption and secretion mechanism of carboxylate drugs].

    PubMed

    Itagaki, Shirou

    2009-11-01

    Oral drug delivery is generally the most desirable means of administration, mainly because of patient acceptance, convenience in administration. Intestinal absorption mechanisms of anionic drugs have been mainly explained by the passive diffusion of nonionized compounds. However, several studies have suggested the involvement of specific transporters in intestinal absorption of weak acids including monocarboxylates. (-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a oral hypoglycemic agent possessing a carboxyl group and a peptide-type bond in its structure. Although nateglinide quickly reaches the maximal serum concentration after oral administration, nateglinide itself is not transported by PepT1 or MCT1. We demonstrated that nateglinide transport occurs via a single system that is H(+) dependent but is distinct from PepT1 or MCT1. In clinical, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many drugs. However, there have been few studies on food-drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial to human health. Polyphenols are commercially prepared and used as functional foods. We reported that ferulic acid, which is widely used as a functional food, affects the transport of clinical agents. The major dose-limiting toxicity after administration of irinotecan hydrochloride, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxycamptothecin (CPT-11) is severe diarrhea. We have found that a specific transport system mediates the uptake of active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) across the apical membrane in Caco-2 cells. Baicalin and sulfobromophthatlein inhibit this transporter. Inhibition of this transporter would be a useful means for reducing late-onset diarrhea.

  17. [The absorption kinetics of oleanolic acid self-microemulsion in rat stomach and intestine].

    PubMed

    Yang, Rui; Su, Le-Qun; Huang, Xin

    2008-11-01

    To study the absorption kinetics of oleanolic acid self-microemulsion in rat stomach and intestine. The absorption kinetics were obtained by using the in situ perfusion method in rat. The absorption of drug was determinated by the decrease in stomach and intestine with the HPLC as the detection method. The absorption percent of oleanolic acid microemulsion for 2 hours was 10.15% in stomach; The absorption rate constants of oleanolic acid microemulsion and micelle were 0.0901/h and 0.0486/h in small intestine, respectively; The best absorption segment in intestine was duodenum, ileum, jejunum and colon by turns. The oleanolic acid self-microemulsifying system significantly enhances the absorption of oleanolic acid in the gastrointestinal tract and improves its bioavailability.

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

    PubMed

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

    2015-09-01

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

  19. 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. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-12-01

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

  1. Intestinal absorption of calcium from calcium ascorbate in rats.

    PubMed

    Tsugawa, N; Yamabe, T; Takeuchi, A; Kamao, M; Nakagawa, K; Nishijima, K; Okano, T

    1999-01-01

    The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

  2. Nutrient sensing by absorptive and secretory progenies of small intestinal stem cells.

    PubMed

    Kishida, Kunihiro; Pearce, Sarah C; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P

    2017-06-01

    Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown; hence we hypothesized that progenitor stem cells (intestinal stem cells, ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet, or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers. We identified nutrient sensing cell type(s) by increased expression of fructolytic genes in response to a fructose challenge. Organoids comprised primarily of enterocytes, Paneth, or goblet, but not ISC, cells responded specifically to fructose without affecting nonfructolytic genes. Sensing was independent of Wnt and Notch modulators and of glucose concentrations in the medium but required fructose absorption and metabolism. More mature enterocyte- and goblet-enriched organoids exhibited stronger fructose responses. Remarkably, enterocyte organoids, upon forced dedifferentiation to reacquire ISC characteristics, exhibited a markedly extended lifespan and retained fructose sensing ability, mimicking responses of some dedifferentiated cancer cells. Using an innovative approach, we discovered that nutrient sensing is likely repressed in progenitor ISCs then irreversibly derepressed during specification into sensing-competent absorptive or secretory lineages, the surprising capacity of Paneth and goblet cells to detect fructose, and the important role of differentiation in modulating nutrient sensing.NEW & NOTEWORTHY Small intestinal stem cells differentiate into several

  3. Factors affecting intestinal absorption of cholesterol and plant sterols and stanols.

    PubMed

    Ikeda, Ikuo

    2015-01-01

    Various factors affect intestinal absorption of cholesterol and plant sterols and stanols. Plant sterols and stanols are generally less absorptive than cholesterol. Differential absorption rates among various plant sterols and stanols have been also reported. Although it was suggested that differential absorption among cholesterol and various plant sterols was determined by difference in excretion rates of sterols and stanols through ATP-binding cassette transporter (ABC) G5/ABCG8 of intestinal cells, our study suggests that affinity for and solubility in bile salt micelles can be important determinants for differential absorption of plant sterols and stanols. It was also suggested that plant sterols were transiently incorporated into intestinal cells and then excreted to intestinal lumen through ABCG5/ABCG8. However, in a rat study, transient incorporation of sitosterol into intestinal cells was not observed, suggesting that sitosterol is differentiated from cholesterol at the incorporation site of intestinal cells. It is well established that plant sterols inhibit intestinal absorption of cholesterol and exert a hypocholesterolemic activity. Plant sterols are solubilized in bile salt micelles as cholesterol. Our study clearly showed that because the sterol-solubilizing capacity of bile salt micelles was limited, plant sterols solubilized in micelles reduced the solubility of cholesterol. This can be the major cause of inhibition of cholesterol absorption by plant sterols. Pancreatic cholesterol esterase accelerates intestinal absorption of unesterified cholesterol. Although it was suggested that cholesterol esterase accelerated esterification of cholesterol incorporated into intestinal cells and acted as a transporter at the surface of intestinal cells, our research revealed that the accelerated cholesterol absorption was caused by hydrolysis of phosphatidylcholine in bile salt micelles. It is thought that hydrolysis of phosphatidylcholine reduces the affinity of

  4. Whey protein effects on energy balance link the intestinal mechanisms of energy absorption with adiposity and hypothalamic neuropeptide gene expression.

    PubMed

    Nilaweera, Kanishka N; Cabrera-Rubio, Raul; Speakman, John R; O'Connor, Paula M; McAuliffe, AnneMarie; Guinane, Caitriona M; Lawton, Elaine M; Crispie, Fiona; Aguilera, Mònica; Stanley, Maurice; Boscaini, Serena; Joyce, Susan; Melgar, Silvia; Cryan, John F; Cotter, Paul D

    2017-07-01

    We tested the hypothesis that dietary whey protein isolate (WPI) affects the intestinal mechanisms related to energy absorption and that the resulting energy deficit is compensated by changes in energy balance to support growth. C57BL/6 mice were provided a diet enriched with WPI with varied sucrose content, and the impact on energy balance-related parameters was investigated. As part of a high-sucrose diet, WPI reduced the hypothalamic expression of pro-opiomelanocortin gene expression and increased energy intake. The energy expenditure was unaffected, but epididymal weight was reduced, indicating an energy loss. Notably, there was a reduction in the ileum gene expression for amino acid transporter SLC6a19, glucose transporter 2, and fatty acid transporter 4. The composition of the gut microbiota also changed, where Firmicutes were reduced. The above changes indicated reduced energy absorption through the intestine. We propose that this mobilized energy in the adipose tissue and caused hypothalamic changes that increased energy intake, acting to counteract the energy deficit arising in the intestine. Lowering the sucrose content in the WPI diet increased energy expenditure. This further reduced epididymal weight and plasma leptin, whereupon hypothalamic ghrelin gene expression and the intestinal weight were both increased. These data suggest that when the intestine-adipose-hypothalamic pathway is subjected to an additional energy loss (now in the adipose tissue), compensatory changes attempt to assimilate more energy. Notably, WPI and sucrose content interact to enable the component mechanisms of this pathway. Copyright © 2017 the American Physiological Society.

  5. Weaning induces both transient and long-lasting modifications of absorptive, secretory, and barrier properties of piglet intestine.

    PubMed

    Boudry, Gaëlle; Péron, Vincent; Le Huërou-Luron, Isabelle; Lallès, Jean Paul; Sève, Bernard

    2004-09-01

    This study investigated intestinal physiology of piglets at weaning. Piglets (n = 60) weaned at 21 d were food deprived for 2 d and then tube-fed using 2 different diets (a conventional diet vs. a wheat-enriched diet). They were slaughtered at d 0, 2, 5, 8, or 15 postweaning. Jejunum, ileum, and colon were mounted in Ussing chambers. In addition, segments of the proximal jejunum of 4 growing pigs were studied 35 d after weaning. Secretory function was assessed by basal short-circuit current (Isc) and secretagogue-stimulated Isc. Glucose absorption was measured by the increase in Isc after the addition of glucose. Epithelial barrier function was measured by transmucosal resistance (R) and horseradish peroxidase (HRP) fluxes across the epithelium. There were no significant differences between the pigs fed the 2 diets for any of the parameters studied. As already reported, a transient villous atrophy was observed. At the same time, we observed an increased basal Isc in jejunum and colon, increased glucose absorption and a dramatic drop of R in jejunum. These parameters had returned to preweaning values by d 5. Weaning was also followed by long-lasting modifications. In jejunum, responses to the secretagogues and glucose absorption were decreased at wk 2 after weaning and were not different between d 15 and 35. Ileal transmucosal resistance increased on d 5 and was stable thereafter. HRP flux in jejunum declined on d 2 and stayed at this low level throughout the experiment. We conclude that weaning induces transient dramatic changes in intestinal physiology but is also a period of maturation of the intestine.

  6. Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

    PubMed

    Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

    2013-12-01

    The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress.

  7. Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

    PubMed Central

    Gardner, M L; Illingworth, K M; Kelleher, J; Wood, D

    1991-01-01

    1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption. PMID:1910085

  8. Lithocholic acid: a new emergent protector of intestinal calcium absorption under oxidant conditions.

    PubMed

    Marchionatti, Ana M; Pérez, Adriana; Rivoira, María A; Rodríguez, Valeria A; Tolosa de Talamoni, Nori G

    2017-04-01

    LCA and 1,25(OH)2D3 are vitamin D receptor ligands with different binding affinity. The secosteroid stimulates intestinal Ca(2+) absorption. Whether LCA alters this process remains unknown. The aim of our work was to determine the effect of LCA on intestinal Ca(2+) absorption in the absence or presence of NaDOC, bile acid that inhibits the cation transport. The data show that LCA by itself did not alter intestinal Ca(2+) absorption, but prevented the inhibitory effect of NaDOC. The concomitant administration of LCA avoided the reduction of intestinal alkaline phosphatase activity caused by NaDOC. In addition, LCA blocked a decrease caused by NaDOC on gene and protein expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption. The oxidative stress and apoptosis triggered by NaDOC were abrogated by LCA co-treatment. In conclusion, LCA placed in the intestinal lumen protects intestinal Ca(2+) absorption against the inhibitory effects caused by NaDOC. LCA avoids the reduction of the transcellular Ca(2+) movement, apparently by blocking the oxidative stress and apoptosis triggered by NaDOC, normalizing the gene and protein expression of molecules involved in Ca(2+) movement. Therefore, LCA might become a possible treatment to improve intestinal calcium absorption under oxidant conditions.

  9. Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate.

    PubMed

    Dyer, Jane; Al-Rammahi, Miran; Waterfall, Louise; Salmon, Kieron S H; Geor, Ray J; Bouré, Ludovic; Edwards, G Barrie; Proudman, Christopher J; Shirazi-Beechey, Soraya P

    2009-06-01

    Experimental and epidemiological evidence suggests that consumption of hydrolyzable carbohydrate, hCHO (grain), by horses is an important risk factor for colic, a common cause of equine mortality. It is unknown whether the small intestinal capacity to digest hCHO and/or to absorb monosaccharides is limiting, or even if horses can adapt to increased carbohydrate load. We investigated changes in the brush-border membrane carbohydrate digestive enzymes and glucose absorptive capacity of horse small intestine in response to increased hCHO. Expression of the Na(+)/glucose co-transporter, SGLT1, was assessed by Western blotting, immunohistochemistry, Northern blotting, QPCR, and Na(+)-dependent D-glucose transport. Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses maintained on a hCHO-enriched diet compared to pasture forage. Activity of the disaccharidases was unaltered by diet. In a well-controlled study, we determined SGLT1 expression in the duodenal and ileal biopsies of horses switched, gradually over a 2-month period, from low (<1.0 g/kg bwt/day) to high hCHO (6.0 g/kg bwt/day) diets of known composition. We show that SGLT1 expression is enhanced, with time, 2-fold in the duodenum and 3.3-fold in the ileum. The study has important implications for dietary management of the horse.

  10. Why we need proper PBPK models to examine intestine and liver oral drug absorption.

    PubMed

    Chow, Edwin C Y; Pang, K Sandy

    2013-01-01

    Intestinal transporters and enzymes are factors that can influence the absorption of orally administrated drugs. Compartmental models are no longer adequate to describe the sequential handling of drugs and metabolites by the intestine and liver during oral drug absorption, especially when intestinal removal is substantial relative to the liver, and when induction/inhibition elicits different extents of change for identical intestinal and hepatic enzymes or transporters. In this review, we described PBPK models for the intestine (with differential flow patterns: traditional model, TM, and segregated flow model, SFM, and QGut model) as well as semi- or whole bodyphysiological- based pharmacokinetic (PBPK) models to describe the impact of the flow pattern, and the intestinal transporters and enzymes and their attendant heterogeneities on intestinal (FI or FG) and oral (Fsys) bioavailability. The modeling efforts have led to a refinement in providing mechanistic insight on the accurate prediction of drug and metabolite profiles for DDI, pharmacogenomics, age factors and disease conditions.

  11. Drug absorption related nephrotoxicity assessment on an intestine-kidney chip.

    PubMed

    Li, Zhongyu; Su, Wentao; Zhu, Yujuan; Tao, Tingting; Li, Dong; Peng, Xiaojun; Qin, Jianhua

    2017-05-01

    Drug absorption in the intestine is tightly related to drug-induced nephrotoxicity, which is a relatively common side effect in clinical practice. It highlights a great need to develop predictive models with high accuracy in the early stage during new drug discovery and development. Herein, we presented a novel intestine-kidney chip, which recapitulated drug absorption in the intestine and its resultant drug toxicity on the kidney. This work aims to provide an integrated tool for accurate assessment of drug absorption-related nephrotoxicity in vitro. A microfluidic device with multi-interfaces was designed, which facilitated the co-culture of the intestinal and glomerular endothelial cells in compartmentalized micro-chambers. Thus, drug absorption and following nephrotoxicity could be explored in a single assay based on the formation of the intact intestine function on the chip. Specifically, we adopt digoxin (DIG) as a model drug combined with colestyramine (COL) or Verapamil (VER), which significantly influence DIG absorption in the intestine. Different degrees of nephrotoxicity under drug combinations were further observed on the chip, including cell apoptosis, cell viability, and lactate dehydrogenase leakage. These features were consistent with the variance of DIG absorption by the intestinal cells. In agreement with clinical observations, our data demonstrated that DIG-induced nephrotoxicity was enhanced combined with VER but weakened with COL. All of these findings suggest that the established microdevice might provide a useful and cost-effective platform in vitro for testing drug absorption and nephrotoxicity in preclinical trials during new drug development.

  12. Mathematical Modeling of Intestinal Iron Absorption Using Genetic Programming

    PubMed Central

    Colins, Andrea; Gerdtzen, Ziomara P.; Nuñez, Marco T.; Salgado, J. Cristian

    2017-01-01

    Iron is a trace metal, key for the development of living organisms. Its absorption process is complex and highly regulated at the transcriptional, translational and systemic levels. Recently, the internalization of the DMT1 transporter has been proposed as an additional regulatory mechanism at the intestinal level, associated to the mucosal block phenomenon. The short-term effect of iron exposure in apical uptake and initial absorption rates was studied in Caco-2 cells at different apical iron concentrations, using both an experimental approach and a mathematical modeling framework. This is the first report of short-term studies for this system. A non-linear behavior in the apical uptake dynamics was observed, which does not follow the classic saturation dynamics of traditional biochemical models. We propose a method for developing mathematical models for complex systems, based on a genetic programming algorithm. The algorithm is aimed at obtaining models with a high predictive capacity, and considers an additional parameter fitting stage and an additional Jackknife stage for estimating the generalization error. We developed a model for the iron uptake system with a higher predictive capacity than classic biochemical models. This was observed both with the apical uptake dataset used for generating the model and with an independent initial rates dataset used to test the predictive capacity of the model. The model obtained is a function of time and the initial apical iron concentration, with a linear component that captures the global tendency of the system, and a non-linear component that can be associated to the movement of DMT1 transporters. The model presented in this paper allows the detailed analysis, interpretation of experimental data, and identification of key relevant components for this complex biological process. This general method holds great potential for application to the elucidation of biological mechanisms and their key components in other complex

  13. Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers.

    PubMed

    Yi, Weiguang; Akoh, Casimir C; Fischer, Joan; Krewer, Gerard

    2006-07-26

    Recent studies have shown that dietary polyphenols may contribute to the prevention of cardiovascular disease and cancer. Anthocyanins from different plant sources including blueberries have been shown to possess potential anticancer activities. One of the key factors needed to correctly relate the in vitro study results to human disease outcomes is information about bioavailability. The objectives of the current study were to evaluate the absorption of blueberry anthocyanin extracts using Caco-2 human intestinal cell monolayers and investigate the effects of different aglycones, sugar moieties, and chemical structure on bioavailability of different types of anthocyanins. The results of this study showed that anthocyanins from blueberries could be transported through the Caco-2 cell monolayers although the transport/absorption efficiency was relatively low compared to other aglycone polyphenols. The transport efficiency of anthocyanins averaged approximately 3-4% [less than 1% in delphinidin glucoside (Dp-glc)]. No significant difference in transport/absorption efficiency was observed among three blueberry cultivars. The observed trends among different anthocyanins generally agreed well with some published in vivo results. Dp-glc showed the lowest transport/absorption efficiency, and malvidin glucoside (Mv-glc) showed the highest transport/absorption efficiency. Our result indicates that more free hydroxyl groups and less OCH(3) groups can decrease the bioavailability of anthocyanins. In addition, cyanindin glucoside (Cy-glc) showed significantly higher transport efficiency than cyanidin galactoside (Cy-gal), and peonidin glucoside (Pn-glc) showed significantly higher transport efficiency than peonidin galactoside (Pn-gal), indicating that glucose-based anthocyanins have higher bioavailability than galactose-based anthocyanins.

  14. Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography.

    PubMed

    Waters, Laura J; Shokry, Dina S; Parkes, Gareth M B

    2016-10-01

    Understanding intestinal absorption for pharmaceutical compounds is vital to estimate the bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems; however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition-absorption relationship. MLC offers many benefits including environmental, economic, time-saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values. Copyright © 2016 John Wiley & Sons, Ltd.

  15. INTESTINAL DIGESTION AND ABSORPTION OF SUGARS AND PEPTIDES.

    DTIC Science & Technology

    Mammalian intestinal sucrase is activated by sodium in different ways in different species. The sodium-activation constants have been determined...Sodium-activation does not follow any compulsory reaction sequence. No diffusion barrier can be detected between lumen and intestinal sucrase ...Trehalase also shows a cooperative interaction between substrate sites. It is not activated by sodium. The intestinal sucrase -isomaltase complex can be

  16. Initial glucose kinetics and hormonal response to a gastric glucose load in unrestrained post-absorptive and starved rats.

    PubMed

    Smadja, C; Morin, J; Ferré, P; Girard, J

    1990-09-01

    A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non-suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential

  17. 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)

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

    ERIC Educational Resources Information Center

    Leese, H. J.

    1984-01-01

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

  19. 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.

  20. Human intestinal absorption--neutral molecules and ionic species.

    PubMed

    Abraham, Michael H

    2014-07-01

    Analysis of percentage human intestinal absorption (%HIA) for 280 drugs shows that an excellent fit can be obtained using only three descriptors for neutral molecules with a SD of 13.9%. Use of descriptors for individual cations and anions does not lead to any better goodness-of-fit. It is noted that diffusion coefficients in water for ionized molecules are almost identical to those for the corresponding neutral molecules. Comparison of equation coefficients for HIA with those for other processes shows that HIA resembles diffusion in water but does not resemble permeation through biological bilayers. It is shown that compound substituent effects on HIA are near those for diffusion but are far away from substituent effects on permeation through a typical bilayer. Calculations indicate that rates of permeation through an unstirred mucosal layer are of the same order as experimental rates of permeation in HIA. It is concluded that for the 280 compound set, diffusion through the unstirred mucosal layer is the rate determining step. The effect on pK(a) in transfer of acids and bases from water to another solvent, and of diffusion past a negative charge in a phase/bilayer is also considered. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  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. Lipid absorption triggers drug supersaturation at the intestinal unstirred water layer and promotes drug absorption from mixed micelles.

    PubMed

    Yeap, Yan Yan; Trevaskis, Natalie L; Porter, Christopher J H

    2013-12-01

    To evaluate the potential for the acidic intestinal unstirred water layer (UWL) to induce drug supersaturation and enhance drug absorption from intestinal mixed micelles, via the promotion of fatty acid absorption. Using a single-pass rat jejunal perfusion model, the absorptive-flux of cinnarizine and (3)H-oleic acid from oleic acid-containing intestinal mixed micelles was assessed under normal acidic microclimate conditions and conditions where the acidic microclimate was attenuated via the co-administration of amiloride. As a control, the absorptive-flux of cinnarizine from micelles of Brij® 97 (a non-ionizable, non-absorbable surfactant) was assessed in the absence and presence of amiloride. Cinnarizine solubility was evaluated under conditions of decreasing pH and decreasing micellar lipid content to assess likely changes in solubilization and thermodynamic activity during micellar passage across the UWL. In the presence of amiloride, the absorptive-flux of cinnarizine and (3)H-oleic acid from mixed micelles decreased 6.5-fold and 3.0-fold, respectively. In contrast, the absorptive-flux of cinnarizine from Brij® 97 micelles remained unchanged by amiloride, and was significantly lower than from the long-chain micelles. Cinnarizine solubility in long-chain micelles decreased under conditions where pH and micellar lipid content decreased simultaneously. The acidic microclimate of the intestinal UWL promotes drug absorption from intestinal mixed micelles via the promotion of fatty acid absorption which subsequently stimulates drug supersaturation. The observations suggest that formulations (or food) containing absorbable lipids (or their digestive precursors) may outperform formulations that lack absorbable components since the latter do not benefit from lipid absorption-induced drug supersaturation.

  3. 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

    2016-07-21

    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.

  4. 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

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

    SciTech Connect

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

    1988-06-01

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

  6. 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.

  7. Digestion and absorption of sugars and sugar substitutes in rat small intestine.

    PubMed

    Tsuji, Y; Yamada, K; Hosoya, N; Moriuchi, S

    1986-02-01

    The bioavailability of newly developed sugar substitutes was observed by measuring the transmural potential difference (delta PD) evoked by Na+-dependent active transport of glucose, which is supposed to be produced by the hydrolysis of sugar substitutes. delta PD was measured using everted intestinal sac prepared from jejunum of adult rats and compared with the digestibility of sugar substitutes in the mucosal homogenate of everted sac. delta PDs evoked by glucose, maltose or maltosylfructose had almost the same levels, however, the delta PD evoked by sucrose was a little lower. delta PDs evoked by maltitol or palatinose were low, and delta PDs evoked by fructo-oligosaccharides were negligible. The hydrolyzing activities of these sugars and sugar substitutes by the mucosal homogenate were correlated with the delta PDs. A significant positive correlation was observed between delta PDmax of various sugars and sugar substitutes and the Vmax of their corresponding hydrolyzing activities. Also, a significant positive correlation was observed between Kt and Km values of these sugars. These results suggest that the absorption of sugar substitutes is dependent on digestibility by membrane digestive enzymes.

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

    PubMed Central

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

    1986-01-01

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

  9. Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K.

    PubMed

    Yamanashi, Yoshihide; Takada, Tappei; Kurauchi, Ryoya; Tanaka, Yusuke; Komine, Toko; Suzuki, Hiroshi

    2017-04-03

    Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

  10. Intestinal ferritin H is required for an accurate control of iron absorption.

    PubMed

    Vanoaica, Liviu; Darshan, Deepak; Richman, Larry; Schümann, Klaus; Kühn, Lukas C

    2010-09-08

    To maintain appropriate body iron levels, iron absorption by the proximal duodenum is thought to be controlled by hepcidin, a polypeptide secreted by hepatocytes in response to high serum iron. Hepcidin limits basolateral iron efflux from the duodenal epithelium by binding and downregulating the intestinal iron exporter ferroportin. Here, we found that mice with an intestinal ferritin H gene deletion show increased body iron stores and transferrin saturation. As expected for iron-loaded animals, the ferritin H-deleted mice showed induced liver hepcidin mRNA levels and reduced duodenal expression of DMT1 and DcytB mRNA. In spite of these feedback controls, intestinal ferroportin protein and (59)Fe absorption were increased more than 2-fold in the deleted mice. Our results demonstrate that hepcidin-mediated regulation alone is insufficient to restrict iron absorption and that intestinal ferritin H is also required to limit iron efflux from intestinal cells.

  11. The Contribution of Intestinal Gluconeogenesis to Glucose Homeostasis Is Low in 2-Day-Old Pigs.

    PubMed

    Cherbuy, Claire; Vaugelade, Pierre; Labarthe, Simon; Honvo-Houeto, Edith; Darcy-Vrillon, Béatrice; Watford, Malcolm; Duée, Pierre-Henri

    2017-03-01

    Background: Active gluconeogenesis is essential to maintain blood glucose concentrations in neonatal piglets because of the high glucose requirements after birth. In several adult mammals, the liver, kidney, and possibly the gut may exhibit gluconeogenesis during fasting and insulinopenic conditions. During the postnatal period, the intestine expresses all of the gluconeogenic enzymes, suggesting the potential for gluconeogenesis. Galactose in milk is a potential gluconeogenic precursor for newborns.Objective: Our aim was to quantify the rate of intestinal glucose production from galactose in piglets compared with the overall rate of glucose production.Methods: A single bolus of [U-(14)C]-galactose was injected into 2-d-old piglets (females and males; mean ± SEM weight: 1.64 ± 0.07 kg) through a gastric catheter. Galactosemia, glycemia, and glucose turnover rate (assessed by monitoring d-[6-(3)H]-glucose) were monitored. Intestinal glucose production from [U-(14)C]-galactose was calculated from [U-(14)C]-glucose appearance in the blood and isotopic dilution. Galactose metabolism was also investigated in vitro in enterocytes isolated from 2-d-old piglets that were incubated with increasing concentrations of galactose.Results: In piglet enterocytes, galactose metabolism was active (mean ± SEM maximum rate of reaction: 2.26 ± 0.45 nmol · min(-1) · 10(6) cells(-1)) and predominantly oriented toward lactate and pyruvate production (74.0% ± 14.5%) rather than glucose production (26.0% ± 14.5%). In conscious piglets, gastric galactose administration led to an increase in arterial galactosemia (from 0 to 1.0 ± 0.8 mmol/L) and glycemia (35% ± 12%). The initial increase in arterial glycemia after galactose administration was linked to an increase in glucose production rate (33% ± 15%) rather than to a decrease in glucose utilization rate (3% ± 6%). The contribution of intestinal glucose production from galactose was <10% of total glucose production in 2-d

  12. Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine.

    PubMed

    Wagner, Brent; Galey, William R

    2003-01-01

    Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile beta-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 microCi D-[(3)H]-mannose and 0.187 microCi D-[(14)C]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[(14)C]-glucose and D-[(3)H]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[(14)C]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants of D-[(14)C]-glucose or D-[(3)H]-mannose transport. However, treatment with 1 mM prunasin (n = 16) did reduce the influx of D-[(14)C]-glucose without affecting D-[(3)H]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1.

  13. Intestinal absorption of lysozyme, an egg-white allergen, in rats: kinetics and effect of NSAIDs.

    PubMed

    Yokooji, Tomoharu; Hamura, Koh; Matsuo, Hiroaki

    2013-08-16

    The absorption pathway(s) of a representative food allergen, lysozyme, and the mechanisms of lysozyme absorption facilitated by non-steroidal anti-inflammatory drugs were examined by intestinal closed-loop and re-circulating perfusion methods in rats. The absorption rate of fluorescein isothiocyanate (FITC)-labeled lysozyme in the proximal intestine was higher than that for a marker of non-specific absorption, FD-10, and was suppressed by colchicine (endocytosis inhibitor). Aspirin increased the absorption of FITC-lysozyme in the proximal intestine with no effects on tissue accumulation. Diclofenac facilitated FITC-lysozyme absorption, but meloxicam and loxoprofen exerted no effects on absorption. Co-administration of misoprostol (synthetic prostaglandin-E1 analog) with aspirin significantly ameliorated the aspirin-facilitated absorption of FITC-lysozyme to the same level as that seen with controls. Thus, lysozyme absorption was mediated by endocytic and paracellular pathways in the proximal intestine, and was facilitated by aspirin and diclofenac after impairment of the paracellular pathway. Misoprostol may suppress the allergen absorption facilitated by aspirin.

  14. Intestinal absorption of hawthorn flavonoids--in vitro, in situ and in vivo correlations.

    PubMed

    Zuo, Zhong; Zhang, Li; Zhou, Limin; Chang, Qi; Chow, Moses

    2006-11-25

    Our previous studies identified hyperoside (HP), isoquercitrin (IQ) and epicatechin (EC) to be the major active flavonoid components of the hawthorn phenolic extract from hawthorn fruits demonstrating inhibitory effect on in vitro Cu(+2)-mediated low density lipoproteins oxidation. Among these three hawthorn flavonoids, EC was the only one detectable in plasma after the oral administration of hawthorn phenolic extract to rats. The present study aims to investigate the intestinal absorption mechanisms of these three hawthorn flavonoids by in vitro Caco-2 monolayer model, rat in situ intestinal perfusion model and in vivo pharmacokinetics studies in rats. In addition, in order to investigate the effect of the co-occurring components in hawthorn phenolic extract on the intestinal absorption of these three major hawthorn flavonoids, intestinal absorption transport profiles of HP, IQ and EC in forms of individual pure compound, mixture of pure compounds and hawthorn phenolic extract were studied and compared. The observations from in vitro Caco-2 monolayer model and in situ intestinal perfusion model indicated that all three studied hawthorn flavonoids have quite limited permeabilities. EC and IQ demonstrated more extensive metabolism in the rat in situ intestinal perfusion model and in vivo study than in Caco-2 monolayer model. Moreover, results from the Caco-2 monolayer model, rat in situ intestinal perfusion model as well as the in vivo pharmacokinetics studies in rats consistently showed that the co-occurring components in hawthorn phenolic extract might not have significant effect on the intestinal absorption of the three major hawthorn flavonoids studied.

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

    PubMed Central

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

    1975-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  18. Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor.

    PubMed

    Cedó, Lídia; Santos, David; Ludwig, Iziar A; Silvennoinen, Reija; García-León, Annabel; Kaipiainen, Leena; Carbó, José M; Valledor, Annabel F; Gylling, Helena; Motilva, Maria-José; Kovanen, Petri T; Lee-Rueckert, Miriam; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

    2017-09-01

    Previous studies have proposed that phytosterols activate liver X receptors (LXR) in the intestine, thereby reducing intestinal cholesterol absorption and promoting fecal cholesterol excretion. In the present study, we examined the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in LXRαβ-deficient mice, and wild-type mice treated with synthetic high-affinity LXRαβ agonists. LXRαβ deficiency led to an induction of intestinal cholesterol absorption and liver cholesterol accumulation. Phytosterol feeding resulted in an approximately 40% reduction of intestinal cholesterol absorption both in wild-type and LXRαβ-deficient mice, reduced dietary cholesterol accumulation in liver and promoted the excretion of fecal cholesterol-derived compounds. Furthermore, phytosterols produced additive inhibitory effects on cholesterol absorption in mice treated with LXRαβ agonists. Our data confirm the effect of LXR in regulating intestinal cholesterol absorption and demonstrate that the cholesterol-lowering effects of phytosterols occur in an LXR-independent manner. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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.

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

    PubMed Central

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

    2014-01-01

    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

  1. 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.

  2. 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.

  3. Lipid-induced peroxidation in the intestine is involved in glucose homeostasis imbalance in mice.

    PubMed

    Serino, Matteo; Waget, Aurélie; 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

    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. 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. 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.

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

    PubMed

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

    2013-01-01

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

  5. Characterizing the dynamic interaction among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese adults.

    PubMed

    Wilbaux, Mélanie; Wölnerhanssen, Bettina K; Meyer-Gerspach, Anne Christin; Beglinger, Christoph; Pfister, Marc

    2017-03-01

    The effects of altered gastric emptying on glucose absorption and kinetics are not well understood in nondiabetic obese adults. The aim of this work was to develop a physiology-based model that can characterize and compare interactions among gastric emptying, glucose absorption, and glycemic control in nondiabetic obese and lean healthy adults. Dynamic glucose, insulin, and gastric emptying (measured with breath test) data from 12 nondiabetic obese and 12 lean healthy adults were available until 180 min after an oral glucose tolerance test (OGTT) with 10, 25, and 75 g of glucose. A physiology-based model was developed to characterize glucose kinetics applying nonlinear mixed-effects modeling with NONMEM7.3. Glucose kinetics after OGTT was described by a one-compartment model with an effect compartment to describe delayed insulin effects on glucose clearance. After the interactions between individual gastric emptying and glucose absorption profiles were accounted for, the glucose absorption rate was found to be similar in nondiabetic obese and lean controls. Baseline glucose concentration was estimated to be only marginally higher in nondiabetic obese subjects (4.9 vs. 5.2 mmol/l), whereas insulin-dependent glucose clearance in nondiabetic obese subjects was found to be cut in half compared with lean controls (0.052 vs. 0.029 l/min) and the insulin concentration associated with 50% of insulin-dependent glucose elimination rate was approximately twofold higher in nondiabetic obese subjects compared with lean controls (7.1 vs. 15.3 μU/ml). Physiology-based models can characterize and compare the dynamic interaction among gastric emptying, glucose absorption and glycemic control in populations of interest such as lean healthy and nondiabetic obese adults. Copyright © 2017 the American Physiological Society.

  6. 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. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  7. 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

  8. 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.

  9. An intrinsic gut leptin-melanocortin pathway modulates intestinal microsomal triglyceride transfer protein and lipid absorption.

    PubMed

    Iqbal, Jahangir; Li, Xiaosong; Chang, Benny Hung-Junn; Chan, Lawrence; Schwartz, Gary J; Chua, Streamson C; Hussain, M Mahmood

    2010-07-01

    Fat is delivered to tissues by apoB-containing lipoproteins synthesized in the liver and intestine with the help of an intracellular chaperone, microsomal triglyceride transfer protein (MTP). Leptin, a hormone secreted by adipose tissue, acts in the brain and on peripheral tissues to regulate fat storage and metabolism. Our aim was to identify the role of leptin signaling in MTP regulation and lipid absorption using several mouse models deficient in leptin receptor (LEPR) signaling and downstream effectors. Mice with spontaneous LEPR B mutations or targeted ablation of LEPR B in proopiomelanocortin (POMC) or agouti gene related peptide (AGRP) expressing cells had increased triglyceride in plasma, liver, and intestine. Furthermore, melanocortin 4 receptor (MC4R) knockout mice expressed a similar triglyceride phenotype, suggesting that leptin might regulate intestinal MTP expression through the melanocortin pathway. Mechanistic studies revealed that the accumulation of triglyceride in the intestine might be secondary to decreased expression of MTP and lipid absorption in these mice. Surgical and chemical blockade of vagal efferent outflow to the intestine in wild-type mice failed to alter the triglyceride phenotype, demonstrating that central neural control mechanisms were likely not involved in the observed regulation of intestinal MTP. Instead, we found that enterocytes express LEPR, POMC, AGRP, and MC4R. We propose that a peripheral, local gut signaling mechanism involving LEPR B and MC4R regulates intestinal MTP and controls intestinal lipid absorption.

  10. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications.

    PubMed

    Cohn, Jeffrey S; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W S; Tandy, Sally

    2010-06-01

    A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals.

  11. 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.

  12. Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

    PubMed Central

    Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

    2001-01-01

    AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

  13. Intestinal absorption of vitamin D: from the meal to the enterocyte.

    PubMed

    Reboul, Emmanuelle

    2015-02-01

    Vitamin D plays key roles in bone, infectious, inflammatory and metabolic diseases. As most people get inadequate sun exposure for sufficient vitamin D status, they need adequate intake of dietary vitamin D. Many studies see optimizing vitamin D status as a public health priority. It is thus vital to gain deeper insight into vitamin D intestinal absorption. It was long assumed that vitamin D intestinal absorption is a passive process, but new data from our laboratory showed that it is actually far more complex than previously thought. This review describes the fate of vitamin D in the human upper gastrointestinal lumen during digestion and focuses on the proteins involved in the intestinal membrane and cellular transport of vitamin D across the enterocyte. Although recent data significantly improve our understanding of vitamin D intestinal absorption, further studies are still needed to increase our knowledge of the molecular mechanisms underlying this phenomenon.

  14. 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.

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

    PubMed

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

    2011-04-01

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

  16. 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

  17. The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed.

    PubMed

    Little, Tanya J; Doran, Selena; Meyer, James H; Smout, Andre J P M; O'Donovan, Deirdre G; Wu, Keng-Liang; Jones, Karen L; Wishart, Judith; Rayner, Christopher K; Horowitz, Michael; Feinle-Bisset, Christine

    2006-09-01

    Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18-59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine ("short-segment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long-segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P < 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long- than during the short-segment infusion (P < 0.05). During the long- but not the short-segment infusion, antral pressure waves (PWs) were suppressed (P < 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon >60 cm of the intestine being exposed to glucose.

  18. 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

    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 (IC(50)) 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 (AUC(last)) 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 AUC(last) 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

  19. 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

  20. Differential responses of intestinal glucose transporter mRNA transcripts to levels of dietary sugars.

    PubMed

    Miyamoto, K; Hase, K; Takagi, T; Fujii, T; Taketani, Y; Minami, H; Oka, T; Nakabou, Y

    1993-10-01

    Dietary sugars are known to stimulate intestinal glucose transport activity, but the specific signals involved are unknown. The Na(+)-dependent glucose co-transporter (SGLT1), the liver-type facilitative glucose transporter (GLUT2) and the intestinal-type facilitative glucose transporter (GLUT5) are all expressed in rat jejunum [Miyamoto, Hase, Taketani, Minami, Oka, Nakabou and Hagihira (1991) Biochem. Biophys. Res. Commun. 181, 1110-1117]. In the present study we have investigated the effects of dietary sugars on these glucose transporter genes. A high-glucose diet stimulated glucose transport activity and increased the levels of SGLT1 and GLUT2 mRNAs in rat jejunum. 3-O-Methylglucose, D-galactose, D-fructose, D-mannose and D-xylose can mimic the regulatory effect of glucose on the SGLT1 mRNA level in rat jejunum. However, only D-galactose and D-fructose increased the levels of GLUT2 mRNA. The GLUT5 mRNA level was increased significantly only by D-fructose. Our results suggest that the increase in intestinal transport activity in rats caused by dietary glucose is due to an increase in the levels of SGLT1 and GLUT2 mRNAs, and that these increases in mRNA may be caused by an enhancement of the transcriptional rate. Furthermore, for expression of the SGLT1 gene, the signal need not be a metabolizable or transportable substrate whereas, for expression of the GLUT2 gene, metabolism of the substrate in the liver may be necessary for signalling. Only D-fructose is an effective signal for expression of the GLUT5 gene.

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

    PubMed

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

    2015-09-02

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

  2. Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice.

    PubMed

    Shim, Jien; Moulson, Casey L; Newberry, Elizabeth P; Lin, Meei-Hua; Xie, Yan; Kennedy, Susan M; Miner, Jeffrey H; Davidson, Nicholas O

    2009-03-01

    FA transport protein 4 (FATP4), one member of a multigene family of FA transporters, was proposed as a major FA transporter in intestinal lipid absorption. Due to the fact that Fatp4(-/-) mice die because of a perinatal skin defect, we rescued the skin phenotype using an FATP4 transgene driven by a keratinocyte-specific promoter (Fatp4(-/-);Ivl-Fatp4(tg/+) mice) to elucidate the role of intestinal FATP4 in dietary lipid absorption. Fatp4(-/-);Ivl-Fatp4(tg/+) mice and wild-type littermates displayed indistinguishable food consumption, growth, and weight gain on either low or high fat (Western) diets, with no differences in intestinal triglyceride (TG) absorption or fecal fat losses. Cholesterol absorption and intestinal TG absorption kinetics were indistinguishable between the genotypes, although Western diet fed Fatp4(-/-);Ivl-Fatp4(tg/+) mice showed a significant increase in enterocyte TG and FA content. There was no compensatory upregulation of other FATP family members or any other FA or cholesterol transporters in Fatp4(-/-);Ivl-Fatp4(tg/+) mice. Furthermore, although serum cholesterol levels were lower in Fatp4(-/-);Ivl-Fatp4(tg/+) mice, there was no difference in hepatic VLDL secretion in-vivo or in hepatic lipid content on either a chow or Western diet. Taken together, our studies find no evidence for a physiological role of intestinal FATP4 in dietary lipid absorption in mice.

  3. Intestinal calcium and lead absorption: Effects of dietary lead and calcium

    SciTech Connect

    Fullmer, C.S. )

    1991-04-01

    The combined effects of dietary calcium (Ca) and lead (Pb) status on intestinal Ca and Pb absorption and related parameters were investigated in young growing chicks. Dietary Pb intake resulted in two remarkable, apparently independent and essentially opposite effects on intestinal Ca and Pb absorption, depending on dietary Ca and Pb levels and duration of treatment. The initial response (1 week) to Ca deficiency was stimulated Ca absorption and calbindin-D level, regardless of dietary Pb intake. The later response (2 weeks) was a reversal, by Pb, of the early phase stimulation. Intestinal Pb absorption was similarly enhanced by Ca deficiency initially, and this response was also inhibited by prolonged dietary Pb intake. Ingestion of Pb by chicks fed adequate Ca resulted is generally elevated intestinal Ca absorption and calbindin-D levels after both 1 and 2 weeks. Intestinal Pb absorption was also increased in the adequate Ca situation, but only after 2 weeks at the lower levels of dietary Pb. The results underscore the complicated nature of Pb-Ca interactions and demonstrate the importance of thorough characterization of the animal model system.

  4. Lanthanide-stimulated glucose and proline transport across rabbit intestinal brush-border membranes.

    PubMed

    Stevens, B R; Kneer, C

    1988-07-07

    Trivalent cations of the lanthanide series (La3+----Yb3+) stimulated uptake of proline or glucose in rabbit small intestinal brush-border membrane vesicles. The lanthanides stimulated uptake to an extent greater than Al3+, choline, and in many cases, Na+. A time-course of Er3+-stimulated glucose uptake gave initial rates and overshoots greater than Na+ stimulation. The best activators were Sm3+, Eu3+ and Tm3+, which stimulated proline initial uptakes by 400-600%, and stimulated glucose uptake by 120-150%, compared to Na+. The best lanthanide cotransport activators possessed high third ionization potentials.

  5. 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.

  6. Intestinal Glycolysis Visualized by FDG PET/CT Correlates With Glucose Decrement After Gastrectomy.

    PubMed

    Ku, Cheol Ryong; Lee, Narae; Hong, Jae Won; Kwon, In Gyu; Hyung, Woo Jin; Noh, Sung Hoon; Lee, Eun Jig; Yun, Mijin; Cho, Arthur

    2017-02-01

    Gastrectomy method is known to influence glucose homeostasis. (18)F-fluoro-2-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) images acquired after gastrectomy often reveals newly developed physiological small bowel uptake. We correlated newly developed small bowel FDG uptake and glucose homeostasis in postgastrectomy gastric cancer patients. We retrospectively analyzed 239 patients without diabetes who underwent staging and follow-up FDG PET/CT scanning before and after gastrectomy for gastric cancer. Postoperative small bowel glycolysis was quantified by recording intestinal total lesion glycolysis (TLG). TLG was assessed with regard to surgical method (Billroth I, Billroth II [BII], Roux-en-Y [RY]), fasting glucose decrement (≥10 mg/dL), and other clinical factors. Patients' weight, fasting glucose, cholesterol, TLG, and body fat levels significantly decreased after surgery. The glucose decrement was significantly associated with fasting glucose, surgical methods, total cholesterol, TLG, and total body fat on univariate analysis. Multivariate analysis showed that BII surgery (odds ratio 6.51) and TLG (odds ratio 3.17) were significantly correlated with glucose decrement. High small bowel glycolysis (TLG >42.0 g) correlated with glucose decrement in RY patients. Newly developed small bowel glycolysis on postgastrectomy FDG PET/CT scanning is correlated with a glucose decrement. These findings suggest a potential role of FDG PET/CT scanning in the evaluation of small bowel glycolysis and glucose control. © 2017 by the American Diabetes Association.

  7. [Effect of various coumarins on the intestinal absorption of galactose in vivo (author's transl)].

    PubMed

    Ruano, M J; Bolufer, J; Larralde, J; Lluch, M

    1975-06-01

    The effect of various coumarins on the active transport of galactose by small intestine in chick and rat was studied, using the in vivo technique of sucessive absorptions. A 10(-4) M concentration of the different coumarins inhibits the absorption of galactose in the chick. This effect persists in successive absorptions without coumarin. In rat, inhibition of galactose active transport by coumarins was observed at 10(-3) M concentration.

  8. Effect of vitamin D on the intestinal absorption of 203Pb and 47Ca in chicks

    SciTech Connect

    Mykkaenen, H.M.; Wasserman, R.H.

    1982-03-01

    The transfer of 203Pb and/or 47Ca across the intestinal epithelium of the chick was investigated, with emphasis given to the functional role of cholecalciferol (vitamin D-3). 203Pb, after introduction in the intestinal lumen, is rapidly accumulated by the intestinal tissue, and only a fraction of 203Pb is translocated parenterally (absorbed). Cholecalciferol did not significantly affect the accumulation of 203Pb by intestinal tissue but did accelerate 203Pb movement across the basal-lateral membrane. In contrast, cholecalciferol both decreased 47Ca tissue levels and increased 47Ca absorption. In rachitic chicks, the rate of absorption of 203Pb was greater in the distal than in the proximal segments of the intestine; after cholecalciferol repletion, the degree of absorption in al segments was similar, indicting the order of cholecalciferol effectiveness as duodenum greater than or equal to jejunum greater than ileum. An acute dose of 1,25(OH)2D3 to rachitic chicks also enhanced both 203Pb and 47Ca absorption, but the time course and pattern of absorption of these metal cations differed. The time at which the absorption of 203Pb peaked and returned to base-line occurred sooner than for 47Ca. Also the back-flux (blood leads to intestinal lumen) of 47Ca was enhanced by cholecalciferol, whereas no effect on the back-flux of 203Pb was noted. These studies show that cholecalciferol and 1,25(OH)2D3 affects both the 203Pb and 47Ca absorptive processes, but the nature of these responses are not identical, suggesting differences in the transport path or the macromolecular interactions of these metal ions during the course of absorption, or both.

  9. Intestinal Lymphatic Transport: an Overlooked Pathway for Understanding Absorption of Plant Secondary Compounds in Vertebrate Herbivores.

    PubMed

    Kohl, Kevin D; Dearing, M Denise

    2017-03-01

    Herbivores employ numerous strategies to reduce their exposure to toxic plant secondary chemicals (PSCs). However, the physiological mechanisms of PSC absorption have not been extensively explored. In particular, the absorption of PSCs via intestinal lymphatic absorption has been largely overlooked in herbivores, even though this pathway is well recognized for pharmaceutical uptake. Here, we investigated for the first time whether PSCs might be absorbed by lymphatic transport. We fed woodrats (Neotoma albigula) diets with increasing concentrations of terpene-rich juniper (Juniperus monosperma) either with or without a compound that blocks intestinal lymphatic absorption (Pluronic L-81). Woodrats consuming diets that contained the intestinal lymphatic absorption blocker exhibited increased food intakes and maintained higher body masses on juniper diets. Our study represents the first demonstration that PSCs may be absorbed by intestinal lymphatic absorption. This absorption pathway has numerous implications for the metabolism and distribution of PSCs in the systemic circulation, given that compounds absorbed via lymphatic transport bypass first-pass hepatic metabolism. The area of lymphatic transport of PSCs represents an understudied physiological pathway in plant-herbivore interactions.

  10. [Studies on absorption kinetics of scopoletin in rat stomachs and intestines].

    PubMed

    Xia, Yu-feng; Dai, Yue; Meng, Qing-yu; Wang, Qiang; Qiu, Ling-ling

    2008-08-01

    To study absorption kinetics of scopoletin in rat stomachs and intestines. Rats was cannulated for in situ recirculation. UV and HPLC methods were used to determine the concentrations of phenolsulfonphthalein and scopoletin, respectively. The absorption rates in rat stomachs at 2 h after administration was 76.31%; The absorption rates at colon, duodenum, ileum and jejunum were 46.25%, 40.54%, 38.21%, 32.77%, respectively. The absorption rate constant (Ka) at concentrations of 10.0144, 20.0288-40.0576 mg x L(-1) in intestine were 0.6434, 0.6137, 0.5970 h(-1), respectively. The Ka of scopoletin at pH of 6.0, 6.8 and 7.4 in intestine were 0.6217, 0.6033, 0.6137 h(-1), respectively. The concentrations and pH values of scopoletin solution had no distinctive effect on the absorption kinetics. The absorption of scopoletin was a first-order process with passive diffusion mechanism. Scopoletin was well absorbed at stomachs and intestines in rats. Colon was the best absorption site of scopoletin, which suggest that a sustained-release preparation should be suitable for this compound.

  11. Intestinal absorption and malnutrition in patients with the acquired immunodeficiency syndrome (AIDS).

    PubMed

    Ott, M; Wegner, A; Caspary, W F; Lembcke, B

    1993-11-01

    The relation of small intestinal dysfunction and malnutrition (body composition and serum index parameters of nutrition) was investigated in 36 male patients with AIDS. Mucosal absorptive capacity was assessed by the 25 g D-xylose test. D-xylose absorption (2 h - serum profile and 5 h - urine) classified 17 patients as having impaired and 19 patients as having normal absorption. In both groups body weight, body mass index as well as body composition analysis indicated malnutrition when compared to healthy male controls (n = 340) or asymptomatic HIV-infected patients (n = 26). Patients with abnormal D-xylose test had more severe malnutrition indicated by a lower body cell mass (17.7 +/- 5.4 vs. 22.5 +/- 4.5 kg; p < 0.01) and an increased ratio of extracellular mass to body cell mass (1.99 +/- 0.82 vs. 1.45 +/- 0.46 p < 0.01). Total serum protein, albumin, cholinesterase activity, cholesterol and LDL were significantly diminished in AIDS-patients with abnormal D-xylose test compared to those with normal D-xylose absorption. Intestinal dysfunction indicated by decreased D-xylose Intestinal dysfunction indicated by decreased D-xylose absorption thus represents an important feature of malnutrition and wasting, and patients with abnormal D-xylose absorption have more profound impairment of body composition, visceral proteins and lipids reflecting malnutrition than patients with unaffected intestinal absorption.

  12. Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves.

    PubMed

    Shimizu, K; Iino, A; Nakajima, J; Tanaka, K; Nakajyo, S; Urakawa, N; Atsuchi, M; Wada, T; Yamashita, C

    1997-04-01

    Extracts containing gymnemic acids, which were extracted from the leaves of Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on glucose transport mediated by the difference of glucose-evoked transmural potential difference (delta PD) in the inverted intestine of guinea-pig and rat, and on blood glucose in rat. Among nine fractions obtained by high performance liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance test, f-2 and f-4 suppressed the elevation of blood glucose level. Both f-2 and f-4 suppressed the contraction of guinea-pig ileal longitudinal muscle, interfered with the increase in delta PD induced by glucose in the inverted intestines of guinea-pig and rat, and inhibited the elevation of blood glucose level. In conclusion, it is suggested that some of the extracts containing gymnemic acids from GS leaves suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestine.

  13. 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.

  14. L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats

    PubMed Central

    Tong, Haiou; Tang, Shaoxun; Han, Xuefeng; Zhou, Chuanshe

    2017-01-01

    L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight) per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration. PMID:28812027

  15. L-Theanine Administration Modulates the Absorption of Dietary Nutrients and Expression of Transporters and Receptors in the Intestinal Mucosa of Rats.

    PubMed

    Yan, Qiongxian; Tong, Haiou; Tang, Shaoxun; Tan, Zhiliang; Han, Xuefeng; Zhou, Chuanshe

    2017-01-01

    L-theanine has various advantageous functions for human health; whether or not it could mediate the nutrients absorption is unknown yet. The effects of L-theanine on intestinal nutrients absorption were investigated using rats ingesting L-theanine solution (0, 50, 200, and 400 mg/kg body weight) per day for two weeks. The decline of insulin secretion and glucose concentration in the serum was observed by L-theanine. Urea and high-density lipoprotein were also reduced by 50 mg/kg L-theanine. Jejunal and ileac basic amino acids transporters SLC7a1 and SLC7a9, neutral SLC1a5 and SLC16a10, and acidic SLC1a1 expression were upregulated. The expression of intestinal SGLT3 and GLUT5 responsible for carbohydrates uptake and GPR120 and FABP2 associated with fatty acids transport were inhibited. These results indicated that L-theanine could inhibit the glucose uptake by downregulating the related gene expression in the small intestine of rats. Intestinal gene expression of transporters responding to amino acids absorption was stimulated by L-theanine administration.

  16. Is apolipoprotein A-IV rate limiting in the intestinal transport and absorption of triglyceride?

    PubMed

    Kohan, Alison B; Wang, Fei; Li, Xiaoming; Vandersall, Abbey E; Huesman, Sarah; Xu, Min; Yang, Qing; Lou, Danwen; Tso, Patrick

    2013-06-15

    Apolipoprotein A-IV (apoA-IV) is synthesized by the intestine and secreted when dietary fat is absorbed and transported into lymph associated with chylomicrons. We have recently demonstrated that loss of apoA-IV increases chylomicron size and delays its clearance from the blood. There is still uncertainty, however, about the precise role of apoA-IV on the transport of dietary fat from the intestine into the lymph. ApoA-IV knockout (KO) mice do not have a gross defect in dietary lipid absorption, as measured by oral fat tolerance and fecal fat measurements. Here, using the in vivo lymph fistula mouse model, we show that the cumulative secretion of triglyceride (TG) into lymph in apoA-IV KO mice is very similar to that of wild-type (WT) mice. However, the apoA-IV KO mice do have subtle changes in TG accumulation in the intestinal mucosa during a 6-h continuous, but not bolus, infusion of lipid. There are no changes in the ratio of esterified to free fatty acids in the intestinal mucosa of the apoA-IV KO, however. When we extended these findings, by giving a higher dose of lipid (6 μmol/h) and for a longer infusion period (8 h), we found no effect of apoA-IV KO on intestinal TG absorption. This higher lipid infusion most certainly stresses the intestine, as we see a drastically lower absorption of TG (in both WT and KO mice); however, the loss of A-IV does not exacerbate this effect. This supports our hypothesis that apoA-IV is not required for TG absorption in the intestine. Our data suggest that the mechanisms by which the apoA-IV KO intestine responds to intestinal lipid may not be different from their WT counterparts. We conclude that apoA-IV is not required for normal lymphatic transport of TG.

  17. Effect of intravenous ranitidine and omeprazole on intestinal absorption of water, sodium, and macronutrients in patients with intestinal resection

    PubMed Central

    Jeppesen, P; Staun, M; Tjellesen, L; Mortensen, P

    1998-01-01

    Background—H2 receptor blockers and proton pump inhibitors reduce intestinal output in patients with short bowel syndrome. 
Aims—To evaluate the effect of intravenous omeprazole and ranitidine on water, electrolyte, macronutrient, and energy absorption in patients with intestinal resection. 
Methods—Thirteen patients with a faecal weight above 1.5 kg/day (range 1.7-5.7 kg/day and a median small bowel length of 100cm were studied. Omeprazole 40 mg twice daily or ranitidine 150mg twice daily were administered for five days in a randomised, double blind, crossover design followed by a three day control period with no treatment. Two patients with a segment of colon in continuation were excluded from analysis which, however, had no influence on the results. 
Results—Omeprazole increased median intestinal wet weight absorption compared with no treatment and ranitidine (p<0.03). The effect of ranitidine was not significant. Four patients with faecal volumes below 2.6 kg/day did not respond to omeprazole; in two absorption increased by 0.5-1 kg/day; and in five absorption increased by 1−2 kg/day. Absorption of sodium, calcium, magnesium, nitrogen, carbohydrate, fat, and total energy was unchanged. Four high responders continued on omeprazole for 12-15 months, but none could be weaned from parenteral nutrition. 
Conclusion—Omeprazole increased water absorption in patients with faecal output above 2.50 kg/day. The effect varied significantly and was greater in patients with a high output, but did not allow parenteral nutrition to be discontinued. Absorption of energy, macronutrients, electrolytes, and divalent cations was not improved. The effect of ranitidine was not significant, possibly because the dose was too low. 

 Keywords: short bowel syndrome; human; diarrhoea; ranitidine; omeprazole PMID:9824602

  18. Intestinal absorption, metabolism, and excretion of (-)-epicatechin in healthy humans assessed by using an intestinal perfusion technique.

    PubMed

    Actis-Goretta, Lucas; Lévèques, Antoine; Rein, Maarit; Teml, Alexander; Schäfer, Christian; Hofmann, Ute; Li, Hequn; Schwab, Matthias; Eichelbaum, Michel; Williamson, Gary

    2013-10-01

    (-)-Epicatechin is a dietary flavonoid present in many foods that affects vascular function, but its action is limited by incomplete absorption, conjugation, and metabolism. Factors that influence this activity may be attributed to instability in the gastrointestinal lumen, low permeability across the intestinal wall, or active efflux from enterocytes and extensive conjugation. With the use of a multilumen perfusion catheter, we investigated the jejunal absorption, systemic availability, metabolism, and intestinal, biliary, and urinary excretion of (-)-epicatechin in humans. In a single-center, randomized, open, controlled study in 8 healthy volunteers, 50 mg purified (-)-epicatechin was perfused into an isolated jejunal segment together with antipyrine as a marker for absorption. (-)-Epicatechin and conjugates were measured in intestinal perfusates, bile, plasma, and urine. Forty-six percent of the dose was recovered in the perfusate either as unchanged (-)-epicatechin (22 mg) or conjugates (0.8 mg); with stability taken into account, this result indicates that ∼46% of the dose had apparently been absorbed. The conjugates were predominantly sulfates, which indicated conjugation by sulfotransferases followed by efflux from the enterocytes. In contrast, epicatechin glucuronides were dominant in plasma, bile, and urine. Almost one-half of the (-)-epicatechin is apparently absorbed in the jejunum but with substantial interindividual differences in the extent of absorption. The data suggest that the nature and substitution position of (-)-epicatechin conjugation are major determinants of the metabolic fate in the body, influencing whether the compound is effluxed into the lumen or absorbed into the blood and subsequently excreted.

  19. [Rat intestinal absorption trait of peimine and peiminine in Thunberg fritillary bulb extract].

    PubMed

    Guan, Zhi-Yu; Zhang, Li-Hua; Chen, Li-Hua; Zhu, Wei-Feng; Liu, Hong-Ning

    2013-12-01

    To study the in situ intestinal absorption kinetics and compatibility influence of peimine and peiminine in rats, the absorption of peimine and peiminine in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC-ELSD. Perfusion rate, pH, concentration of drug, gender and bile duct ligation can significantly affect the absorption of peimine and peiminine, the Ka, and Papp values in the condition of pH 6.8 and pH 7.4 had significant difference (P<0.01), as drug concentration irlcreased, the absorption parameters of peimine and peiminine decreased, Ka and Papp between low concentrations and middle concentrations was significant difference (P<0.01). Verapamil can not affect Ka and Papp of peimine and peiminine which are in the extract (P> 0.05). Bitter almonds and licorice can significantly reduce the absorption of peimine and peiminine with the usual dose (P<0.01), extracted separately and together had no significant difference on Ka and Papp (P> 0.05). Experimental results show that the absorption features of peimine and peiminine are basically the same, both of them could be absorbed at all segments of the intestine in rats and had no special absorption window, and with significant differences between male and female individuals. The absorption of peimine and peiminine complies with the active transport and facilitated diffusion in the general intestinal segments. Bitter almond and licorice can reduce the intestinal absorption rate ofpeimine and peiminine.

  20. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (-)-epigallocatechin gallate.

    PubMed

    Dube, Admire; Nicolazzo, Joseph A; Larson, Ian

    2010-10-09

    Catechins found in green tea have received considerable attention due to their favourable biological properties which include cardioprotective, neuroprotective and anti-cancer effects. However, their therapeutic potential is limited by their low oral bioavailability, attributed to poor stability and intestinal absorption. We encapsulated (+)-catechin (C) and (-)-epigallocatechin gallate (EGCg) in chitosan nanoparticles (CS NP) as a means of enhancing their intestinal absorption. Using excised mouse jejunum in Ussing chambers, encapsulation significantly enhanced (p<0.05) intestinal absorption. The cumulative amounts transported after encapsulation were significantly higher (p<0.05), i.e. 302.1+/-46.1 vs 206.8+/-12.6ng/cm(2) and 102.7+/-12.4 vs 57.9+/-7.9ng/cm(2) for C and EGCg, respectively. The mechanism by which absorption was enhanced was not through an effect of CS NPs on intestinal paracellular or passive transcellular transport processes (as shown by transport of (14)C-mannitol and (3)H-propranolol) or an effect on efflux proteins (as shown by transport of (3)H-digoxin) but was likely due to stabilization of catechins after encapsulation (99.7+/-0.7 vs 94.9+/-3.8% and 56.9+/-3.0 vs 1.3+/-1.7% of the initial C and EGCg concentration remaining, respectively). This study demonstrates that encapsulation of catechins in CS NPs enhances their intestinal absorption and is a promising strategy for improving their bioavailability.

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

    PubMed

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

    2014-09-01

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

  2. 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

  3. 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.

  4. 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.

  5. Amino acid and peptide absorption after proximal small intestinal resection in the rat.

    PubMed Central

    Garrido, A B; Freeman, H J; Chung, Y C; Kim, Y S

    1979-01-01

    In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation. PMID:428822

  6. Intestinal Digestion and Absorption of Sugars and Peptides.

    DTIC Science & Technology

    The sucrase -isomaltase complex, as prepared from the small intestine by papain solubilisation and Sephadex chromatography, has a ml. wt. of...approximately 190 000 and is composed of 6 subunits. Its amino acid composition, its content in SH and SS groups have been determined. The sucrase -isomaltase

  7. Intestinal adaptation in patients with short bowel syndrome. Measurement by calcium absorption

    SciTech Connect

    Gouttebel, M.C.; Saint Aubert, B.; Colette, C.; Astre, C.; Monnier, L.H.; Joyeux, H. )

    1989-05-01

    Functional adaptation of remaining intestine was evaluated in 30 patients with extensive small bowel resection. Calcium and xylose absorption tests were compared. Calcium absorption was measured by a double-radiotracer technique. Serum xylosemia was measured 2 hr after D-xylose ingestion. Patients were divided into two groups according to the time interval between surgery and evaluation: less (group I) or more (group II) than two years. A statistically significant correlation was found between xylosemia and remaining small bowel length (r = 0.71; P less than 0.001) and between calcium absorption and remaining small bowel length (r = 0.75; P less than 0.001) in group I. A significant correlation was also observed between calcium absorption and time after surgery (r = 0.65; P = 0.001) but not for xylose absorption. Calcium absorption value was significantly increased in group II patients compared with group I patients matched for remaining small bowel length (36.2 +/- 12.5% vs 14.5 +/- 9.1%; P less than 0.001) while no difference was observed between the two groups concerning xylose absorption. These data indicate that intestinal calcium absorption continues to increase for more than two years after a major bowel resection in man. The intestine does not seem to recover all its functions at the same time.

  8. Enhanced ex vivo intestinal absorption of olmesartan medoxomil nanosuspension: Preparation by combinative technology.

    PubMed

    Attari, Zenab; Bhandari, Amita; Jagadish, P C; Lewis, Shaila

    2016-01-01

    The purpose of this study was to develop nanosuspension based on combinative technology to enhance the intestinal absorption of Olmesartan medoxomil (OLM), a potent antihypertensive agent with limited oral bioavailability. Two combinative approaches were employed and then characterized. In vitro intestinal absorption of OLM nanosuspension and plain OLM was studied using non-everted rat intestinal sac model. Optimal OLM nanosuspension was prepared by a combination of ball milling and probe sonication using stabilizer, Poloxamer 407. The formula exhibited particle size of 469.9 nm and zeta potential of -19.1 mV, which was subjected to ex vivo studies. The flux and apparent permeability coefficient in intestine from OLM nanosuspension was higher than the plain drug, thereby suggesting better drug delivery.

  9. Intestinal barrier function and absorption in pigs after weaning: a review.

    PubMed

    Wijtten, Peter J A; van der Meulen, Jan; Verstegen, Martin W A

    2011-04-01

    Under commercial conditions, weaning of piglets is associated with social, environmental and dietary stress. Consequently, small-intestinal barrier and absorptive functions deteriorate within a short time after weaning. Most studies that have assessed small-intestinal permeability in pigs after weaning used either Ussing chambers or orally administered marker probes. Paracellular barrier function and active absorption decrease when pigs are weaned at 3 weeks of age or earlier. However, when weaned at 4 weeks of age or later, the barrier function is less affected, and active absorption is not affected or is increased. Weaning stress is a critical factor in relation to the compromised paracellular barrier function after weaning. Adequate feed intake levels after weaning prevent the loss of the intestinal barrier function. Transcellular transport of macromolecules and passive transcellular absorption decrease after weaning. This may reflect a natural intestinal maturation process that is enhanced by the weaning process and prevents the pig from an antigen overload. It seems that passive and active absorption after weaning adapt accurately to the new environment when pigs are weaned after 3 weeks of age. However, when weaned at 3 weeks of age or earlier, the decrease in active absorption indicates that pigs are unable to sufficiently adapt to the new environment. To improve weaning strategies, future studies should distinguish whether the effect of feed intake on barrier function can be directed to a lack of a specific nutrient, i.e. energy or protein.

  10. Variations of intestinal calcium absorption in adult frogs (Rana esculenta). Effect of lysine.

    PubMed

    el Maraghi-Ater, H; Hourdry, J; Mesnard, J; Dupuis, Y

    1987-01-01

    Intestinal calcium absorption was investigated in an adult frog (Rana esculenta) by injecting a CaCl2 solution containing 45Ca into the lumen. The 45Ca absorption coefficient in the proximal loop was higher than in the distal loop, only when the CaCl2 solution was left for 4 h. This coefficient increased both in the proximal and distal loops when a 4-h treatment was substituted for a 1-h treatment. The coefficient increased in the whole intestine during the first 2 h of treatment (1 h: 21%; 2 h: 55%) and remained stable afterwards in our experimental conditions. The intestinal calcium absorption increase occurred early in the presence of L-lysine (100 mM), since the coefficient already reached its maximum value (52%) after a 1-h treatment.

  11. Mucosal iron in the control of iron absorption in a rat intestinal transplant model

    SciTech Connect

    Adams, P.C.; Zhong, R.; Haist, J.; Flanagan, P.R.; Grant, D.R. )

    1991-02-01

    Isogeneic intestinal transplantation of iron-loaded and iron-deficient intestine into iron-deficient rats was performed in 20 Lewis rats to isolate the effect of intestinal mucosal iron on iron absorption. Rats were iron loaded with three weekly IM injections of 50 mg of iron dextran and were rendered iron deficient with an iron-deficient diet for 3 weeks. Iron status was assessed by hepatic and gut mucosal iron determination. Uptake and transfer of 59Fe-ascorbate was measured in an isolated perfused segment of transplanted intestine 48 hours after transplantation. The mean rate of uptake of 59Fe from an iron-loaded intestine (mean mucosal iron concentration, 7.97 +/- 2.02 mumol/g) was 431 +/- 27 nmol/30 min, and from an iron-deficient intestine (mean mucosal iron concentration, 1.35 +/- .84 mumol/g), 743 +/- 222 nmol/30 min (P less than 0.001). The mean transfer of 59Fe from the mucosal cell to the body through an iron-loaded intestine was 63 +/- 22 nmol/30 min, and through an iron-deficient intestine was 86 +/- 32 nmol/30 min (P less than 0.05). These results suggest that the gut mucosal iron concentration regulates the uptake and transfer of iron in the intestine.

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

    PubMed

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

    2013-05-06

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

  13. Hyperenteroglucagonaemia and small intestinal mucosal growth after colonic perfusion of glucose in rats.

    PubMed Central

    Miazza, B M; Al-Mukhtar, M Y; Salmeron, M; Ghatei, M A; Felce-Dachez, M; Filali, A; Villet, R; Wright, N A; Bloom, S R; Crambaud, J C

    1985-01-01

    Beside intraluminal factors, humoral agents play an important role in intestinal adaptation. Enteroglucagon, the mucosal concentration of which is maximal in the terminal ileum and colon, is the strongest candidate for the role of small intestinal mucosal growth factor. The present experiment was designed to study the role of colonic enteroglucagon in stimulating mucosal growth in rats with a normal small intestine. After eight days of glucose large bowel perfusion, enteroglucagon plasma concentrations were 120.7 +/- SEM 9.2 pmol/l, versus 60.1 +/- 6.8 in mannitol perfused control rats (p less than 0.001). Gastrin, cholecystokinin, neurotensin, pancreatic glucagon, and insulin plasma concentrations were unchanged. Crypt cell proliferation, measured by the vincristine metaphase arrest technique, increased significantly in the small intestine of glucose perfused animals (p less than 0.005-0.001) in comparison with the controls. This resulted in a greater mucosal mass in both proximal and distal small bowel: mucosal wet weight, DNA, protein and alpha D-glucosidase per unit length intestine were all significantly higher (p less than 0.05-0.001) than in mannitol perfused rats. Our data, therefore, support the hypothesis that enteroglucagon is an enterotrophic factor and stress the possible role of the colon in the regulation of small bowel trophicity. PMID:3996942

  14. Functional involvement of RFVT3/SLC52A3 in intestinal riboflavin absorption.

    PubMed

    Yoshimatsu, Hiroki; Yonezawa, Atsushi; Yao, Yoshiaki; Sugano, Kumiko; Nakagawa, Shunsaku; Omura, Tomohiro; Matsubara, Kazuo

    2014-01-01

    Riboflavin, also known as vitamin B2, is transported across the biological membrane into various organs by transport systems. Riboflavin transporter RFVT3 is expressed in the small intestine and has been suggested to localize in the apical membranes of the intestinal epithelial cells. In this study, we investigated the functional involvement of RFVT3 in riboflavin absorption using intestinal epithelial T84 cells and mouse small intestine. T84 cells expressed RFVT3 and conserved unidirectional riboflavin transport corresponding to intestinal absorption. Apical [(3)H]riboflavin uptake was pH-dependent in T84 cells. This uptake was not affected by Na(+) depletion at apical pH 6.0, although it was significantly decreased at apical pH 7.4. The [(3)H]riboflavin uptake from the apical side of T84 cells was prominently inhibited by the RFVT3 selective inhibitor methylene blue and significantly decreased by transfection of RFVT3-small-interfering RNA. In the gastrointestinal tract, RFVT3 was expressed in the jejunum and ileum. Mouse jejunal and ileal permeabilities of [(3)H]riboflavin were measured by the in situ closed-loop method and were significantly reduced by methylene blue. These results strongly suggest that RFVT3 would functionally be involved in riboflavin absorption in the apical membranes of intestinal epithelial cells.

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

    PubMed

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

    2016-03-01

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

  16. 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

    2016-07-05

    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.

  17. 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

  18. Intestinal absorption of pallidifloside D are limited by P-glycoprotein in mice.

    PubMed

    Wang, Ming-Yu; Yang, Ming; Hou, Pi-Yong; Chen, Xiu-Bo; Li, Hong-Gang; Yan, Jiu-Xing; Zhang, Jun; Zhang, Yan-Wen; Wu, Xiao-Hui

    2017-08-03

    1. Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be very effective in hyperuricemic control. But it is poorly bioavailable after oral administration. Here, we determined the role of P-glycoprotein (P-gp) in the intestinal absorption of Pallidifloside D. 2. We found that Pallidifloside D significantly stimulated P-gp ATPase activity in vitro ATPase assay with a small EC50 value of 0.46 μM. 3. In the single-pass perfused mouse intestine model, the absorption of Pallidifloside D was not favored in the small intestine (duodenum, jejunum and ileum) with a P*w value of 0.35-0.78. By contrast, this compound was well-absorbed in the colon with a P*w value of 1.23. The P-gp inhibitors cyclosporine significantly enhanced Pallidifloside D absorption in all four intestinal segments (duodenum, jejunum, ileum and colon) and the fold change ranged from 5.5 to 15.3. Pharmacokinetic study revealed that cyclosporine increased the systemic exposure of Pallidifloside D by a 2.5-fold after oral administration. 4. These results suggest that P-gp-mediated efflux is a limiting factor for intestinal absorption of Pallidifloside D in mice.

  19. Modeling the heterogeneous intestinal absorption of propiverine extended-release.

    PubMed

    Weiss, Michael; Sermsappasuk, Pakawadee; Siegmund, Werner

    2015-08-30

    Propiverine is a widely used antimuscarinic drug with bioavailability that is limited by intestinal first-pass extraction. To study the apparent heterogeneity in intestinal first-pass extraction, we performed a population analysis of oral concentration-time data measured after administration of an extended-release formulation of propiverine in ten healthy subjects. Using an inverse Gaussian function as input model, the assumption that the systemically available fraction increases as a sigmoidal function of time considerably improved the fit. The step-like increase in this fraction at time t=3.7h predicted by the model suggests that propiverine is predominantly absorbed in colon. A nearly perfect correlation was found between the estimates of bioavailability and mean dissolution time. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. 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.

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

    USGS Publications Warehouse

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

    1980-01-01

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

  2. 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.

  3. 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

  4. 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.

  5. Kinetics of phosphorus absorption in ligated small intestinal segments of broilers.

    PubMed

    Liu, S B; Hu, Y X; Liao, X D; Lu, L; Li, S F; Zhang, L Y; Tan, H Z; Yang, L; Suo, H Q; Luo, X G

    2016-08-01

    Two experiments were conducted using 22-d-old Arbor Acres male broilers to study the kinetics of inorganic P absorption and the effect of P treatment on Type IIb sodium-phosphate cotransporter (NaP-IIb) mRNA and protein levels in ligated segments from different intestinal regions. In Exp. 1, the P absorption in different small intestinal segments at different postperfusion times (0, 2.5, 5, 10, 20, or 40 min) were compared. In Exp. 2, different small intestinal loops were perfused with solutions containing 0, 1.5, 3, 6, 12, 24, or 48 mmol P/L as KHPO, and P concentrations in perfusates were determined at 20 min after perfusion. The mRNA levels of NaP-IIb in different small intestinal loops and protein expression levels in the duodenums from the control group and the 6 or 48 mmol P/L group were analyzed. The results from Exp. 1 showed that P absorption increased in an asymptotic response to postperfusion time within 40 min in all the intestinal segments and P absorption was greater ( < 0.04) in the duodenum than in the other 2 segments at 20 min after perfusion, indicating that the duodenum is the main site of P absorption in the small intestine of chicks. In Exp. 2, the kinetic curves showed that P absorption in the duodenum was a saturated carrier mediated process and in the jejunum or ileum occurred with a nonsaturated diffusion process. In addition, the b mRNA levels were greater ( < 0.0001) in the duodenum than in the other 2 segments in the 3 groups (0, 6, or 48 mmol P/L), further indicating that P absorption in the duodenum occurred mainly by a saturated carrier mediated process. However, no significant differences ( = 0.20) in the NaP-IIb protein levels of the duodenum were observed among the 0, 6, and 48 mmol P/L groups. In conclusion, this study suggests by our criteria in ligated intestinal loops that the duodenum is the main site of P absorption and that P absorption may be a saturated carrier mediated process in the duodenum but a nonsaturated diffusion

  6. Recent developments of in silico predictions of intestinal absorption and oral bioavailability.

    PubMed

    Hou, Tingjun; Li, Youyong; Zhang, Wei; Wang, Junmei

    2009-06-01

    Among the absorption, distribution, metabolism, elimination, and toxicity properties (ADMET), unfavorable oral bioavailability is indeed an important reason for stopping further development of the drug candidates. Thus, predictions of oral bioavailability and bioavailability-related properties, especially intestinal absorption are areas in need of progress to aid pharmaceutical drug development. In this article, we review recent developments in the prediction of passive intestinal absorption and oral bioavailability. The advances in the datasets used for model building, the molecular descriptors, the prediction models, and the statistical modeling techniques, are summarized. Furthermore, we compared the performance of one machine learning method, support vector machines (SVM), and one traditional classification method, recursive partitioning (RP), on the predictions of passive absorption. Our comparisons demonstrate that the complex machine learning method could give better predictions than the traditional approach. Finally we discuss the current challenges that remain to be addressed.

  7. The kinetics of intestinal calcium absorption in the rat: an analytical and model building study.

    PubMed

    de Labriolle-Vaylet, C; Bouvet, D; Brezillon, P; Milhaud, G; Staub, J F

    1986-04-01

    The experimental data obtained from in vivo single pass perfusion of duodenal, jejunal, and ileal intestinal segments of 33- and 50-day-old rats have been used to test a series of models for calcium absorption. Each model was checked for the statistical validity and goodness-of-fit with the experimental data. The model adopted for the duodenum and jejunum had two major components, one saturable and the other nonsaturable, and a minor secretory component. This model was not applicable to ileal calcium absorption. Here the secretory component appeared to be much more important, and the absorption parameters varied in such a manner as to suggest that this intestinal segment was capable of short term autoregulation of dietary calcium absorption.

  8. On the use of tritium-labelled albumin for studies of intestinal absorption

    PubMed Central

    Jeejeebhoy, K. N.; Stewart, J. H.; Evans, E. A.; Booth, C. C.

    1964-01-01

    Human serum albumin has been successfully labelled with tritium. It is considerably denatured in the process and has a shorter half life when given intravenously than 131I-labelled albumin. Nevertheless it is satisfactory for absorption studies, although not for turnover observations. These studies on absorption in control subjects and in patients with intestinal malabsorption indicate that the excreted radioactivity may have been derived from endogenous sources rather than from the results of malabsorption alone. PMID:14209918

  9. Stapled Vasoactive Intestinal Peptide (VIP) Derivatives Improve VPAC2 Agonism and Glucose-Dependent Insulin Secretion.

    PubMed

    Giordanetto, Fabrizio; Revell, Jefferson D; Knerr, Laurent; Hostettler, Marie; Paunovic, Amalia; Priest, Claire; Janefeldt, Annika; Gill, Adrian

    2013-12-12

    Agonists of vasoactive intestinal peptide receptor 2 (VPAC2) stimulate glucose-dependent insulin secretion, making them attractive candidates for the treatment of hyperglycaemia and type-II diabetes. Vasoactive intestinal peptide (VIP) is an endogenous peptide hormone that potently agonizes VPAC2. However, VIP has a short serum half-life and poor pharmacokinetics in vivo and is susceptible to proteolytic degradation, making its development as a therapeutic agent challenging. Here, we investigated two peptide cyclization strategies, lactamisation and olefin-metathesis stapling, and their effects on VPAC2 agonism, peptide secondary structure, protease stability, and cell membrane permeability. VIP analogues showing significantly enhanced VPAC2 agonist potency, glucose-dependent insulin secretion activity, and increased helical content were discovered; however, neither cyclization strategy appeared to effect proteolytic stability or cell permeability of the resulting peptides.

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

    SciTech Connect

    Mason, J.B.; Selhub, J.

    1986-03-01

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

  11. 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.

  12. Morphine-neural interactions on canine intestinal absorption and blood flow.

    PubMed Central

    Mailman, D.

    1984-01-01

    Intestinal Na and H2O fluxes and blood flow were determined in extrinsically denervated or innervated ileum of fed dogs during intra-arterial (0.2, 2, 20 micrograms min-1) or intraluminal (4, 40, 400 micrograms ml-1) morphine sulphate infusion. 3H2O and 22Na were used to determine unidirectional fluxes and 3H2O clearances were used to determine total segmental and absorptive site blood flow. Net Na and H2O absorption decreased with time in innervated gut segments but were unchanged in denervated segments. Intra-arterial morphine prevented the decrease in net Na and H2O absorption in innervated segments due to increases in unidirectional absorptive fluxes. Intra-arterial morphine did not affect absorption in denervated segments. Intraluminal morphine increased net Na and H2O absorption from both innervated and denervated ileal segments due to increases in the unidirectional absorptive fluxes. Absorptive site blood flow was linearly related to unidirectional absorptive Na fluxes in each group although not with the same slopes. The increment in absorptive site blood flow vs. absorptive Na flux was greatest with luminal morphine, intermediate with intra-arterial morphine and in denervated segments without morphine and least in innervated segments. It was concluded that intra-arterial morphine inhibits an antiabsorptive effect of extrinsic nerves and that intraluminal morphine promotes an absorptive effect which could be direct or mediated through intrinsic nerves. PMID:6704589

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

    PubMed

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

    2014-09-15

    Guanylin (GN) inhibited water absorption and short-circuit current (Isc) in seawater eel intestine. Similar inhibition was observed after bumetanide, and the effect of bumetanide was abolished by GN or vice versa, suggesting that both act on the same target, Na(+)-K(+)-2Cl(-) cotransporter (NKCC), which is a key player for the Na(+)-K(+)-Cl(-) transport system responsible for water absorption in marine teleost intestine. However, effect of GN was always greater than that of bumetanide: 10% greater in middle intestine (MI) and 40% in posterior intestine (PI) for Isc, and 25% greater in MI and 34% in PI for water absorption. After treatment with GN, Isc decreased to zero, but 20-30% water absorption still remained. The remainder may be due to the Cl(-)/HCO3 (-) exchanger and Na(+)-Cl(-) cotransporter (NCC), since inhibitors for these transporters almost nullified the remaining water absorption. Quantitative PCR analysis revealed the presence of major proteins involved in water absorption; the NKCC2β and AQP1 genes whose expression was markedly upregulated after seawater acclimation. The SLC26A6 (anion exchanger) and NCCβ genes were also expressed in small amounts. Consistent with the inhibitors' effect, expression of NKCC2β was MI > PI, and that of NCCβ was MI < PI. The present study showed that GN not only inhibits the bumetanide-sensitive Na(+)-K(+)-Cl(-) transport system governed by NKCC2β, but also regulates unknown ion transporters different from GN-insensitive SLC26A6 and NCC. A candidate is cystic fibrosis transmembrane conductance regulator Cl(-) channel, as demonstrated in mammals, but its expression is low in eel intestine, and its role may be minor, as indicated by the small effect of its inhibitors. Copyright © 2014 the American Physiological Society.

  14. Effect of chronic ethanol on D-galactose absorption by the rat whole intestinal surface.

    PubMed

    Carreras, O; Vazquez, A L; Rubio, J M; Delgado, M J; Murillo, M L

    1992-01-01

    The in vivo absorption of D-galactose by rat whole intestinal surface after 4 weeks of 30% ethanol ingestion in drinking water has been studied, and the results were compared with ad lib-fed control rats. The total serosal intestinal area was determined by integration obtaining similar values between control and alcohol-treated groups. In the caecum surface of ethanol-fed rats slight but not significant increases were found, while the jejunum area decreased with respect to control rats. Total galactose absorption during 10 min of perfusion was slightly increased in ethanol-fed rats but these results were not significant with the substrate concentrations tested. When absorption data were referred to serosal surface, the absorption/cm2 values in ethanol-fed rats were increased at the studied galactose concentrations although these results were only statistically significant at 10 mM. In conclusion, the present data indicates a slight increase in D-galactose absorptive capacity by the whole intestine in ethanol-fed rats which suggest that the tissue traditionally not evaluated such as caecum and colon could modify the functional response to the absorption nutrients.

  15. Effect of Glycine-Conjugated Bile Acids with and without Lecithin on Water and Glucose Absorption in Perfused Human Jejunum

    PubMed Central

    Wingate, David L.; Phillips, Sidney F.; Hofmann, Alan F.

    1973-01-01

    Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred. Images PMID:4700493

  16. Glucose transporter 1 (GLUT1) expression is associated with intestinal type of gastric carcinoma.

    PubMed Central

    Kim, W. S.; Kim, Y. Y.; Jang, S. J.; Kimm, K.; Jung, M. H.

    2000-01-01

    Increased expression of glucose transporter1 (GLUT1) has been reported in many human cancers. We hypothesized that the degree of GLUT1 might provide a useful biological information in gastric adenocarcinoma. RT-PCR and immunostaining were used to analyze GLUT1 expression in gastric cancer. RT-PCR showed GLUT1 expression was not largely detected in normal gastric tissue but was detected in cancerous gastric tissue of counterpart. By immunohistochemistry, GLUT1 protein was absent in normal gastric epithelium and intestinal metaplasia. 11 of 65 patients with gastric adenocarcinoma had specific GLUT1 immunostaining in a plasma membrane pattern with varied intensities. GLUT1 protein did not show any significant correlation with tumor stage and nodal metastasis (p>0.05 by Mann-Whitney test). However, the positive immunostaining for GLUT1 is associated with intestinal differentiation (p=0.003). Our results suggest that GLUT1 protein is associated with intestinal type of gastric cancer. PMID:10983690

  17. Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus)

    PubMed Central

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Ramesh, Naresh; Delgado, María Jesús; Valenciano, Ana Isabel; Unniappan, Suraj

    2017-01-01

    Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish. PMID:28338019

  18. Ghrelin Facilitates GLUT2-, SGLT1- and SGLT2-mediated Intestinal Glucose Transport in Goldfish (Carassius auratus).

    PubMed

    Blanco, Ayelén Melisa; Bertucci, Juan Ignacio; Ramesh, Naresh; Delgado, María Jesús; Valenciano, Ana Isabel; Unniappan, Suraj

    2017-03-24

    Glucose homeostasis is an important biological process that involves a variety of regulatory mechanisms. This study aimed to determine whether ghrelin, a multifunctional gut-brain hormone, modulates intestinal glucose transport in goldfish (Carassius auratus). Three intestinal glucose transporters, the facilitative glucose transporter 2 (GLUT2), and the sodium/glucose co-transporters 1 (SGLT1) and 2 (SGLT2), were studied. Immunostaining of intestinal sections found colocalization of ghrelin and GLUT2 and SGLT2 in mucosal cells. Some cells containing GLUT2, SGLT1 and SGLT2 coexpressed the ghrelin/growth hormone secretagogue receptor 1a (GHS-R1a). Intraperitoneal glucose administration led to a significant increase in serum ghrelin levels, as well as an upregulation of intestinal preproghrelin, ghrelin O-acyltransferase and ghs-r1 expression. In vivo and in vitro ghrelin treatment caused a concentration- and time-dependent modulation (mainly stimulatory) of GLUT2, SGLT1 and SGLT2. These effects were abolished by the GHS-R1a antagonist [D-Lys3]-GHRP-6 and the phospholipase C inhibitor U73122, suggesting that ghrelin actions on glucose transporters are mediated by GHS-R1a via the PLC/PKC signaling pathway. Finally, ghrelin stimulated the translocation of GLUT2 into the plasma membrane of goldfish primary intestinal cells. Overall, data reported here indicate an important role for ghrelin in the modulation of glucoregulatory machinery and glucose homeostasis in fish.

  19. 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)

  20. 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)

  1. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier.

    PubMed

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

    2016-07-15

    The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd contamination

  2. Oral Administration of Probiotics Inhibits Absorption of the Heavy Metal Cadmium by Protecting the Intestinal Barrier

    PubMed Central

    Zhai, Qixiao; Tian, Fengwei; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan

    2016-01-01

    ABSTRACT The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. Our previous work demonstrated that oral administration of probiotics can significantly inhibit Cd absorption in the intestines of mice, but further evidence is needed to gain insights into the related protection mode. The goal of this study was to evaluate whether probiotics can inhibit Cd absorption through routes other than the Cd binding, with a focus on gut barrier protection. In the in vitro assay, both the intervention and therapy treatments of Lactobacillus plantarum CCFM8610 alleviated Cd-induced cytotoxicity in the human intestinal cell line HT-29 and protected the disruption of tight junctions in the cell monolayers. In a mouse model, probiotics with either good Cd-binding or antioxidative ability increased fecal Cd levels and decreased Cd accumulation in the tissue of Cd-exposed mice. Compared with the Cd-only group, cotreatment with probiotics also reversed the disruption of tight junctions, alleviated inflammation, and decreased the intestinal permeability of mice. L. plantarum CCFM8610, a strain with both good Cd binding and antioxidative abilities, exhibited significantly better protection than the other two strains. These results suggest that along with initial intestinal Cd sequestration, probiotics can inhibit Cd absorption by protecting the intestinal barrier, and the protection is related to the alleviation of Cd-induced oxidative stress. A probiotic with both good Cd-binding and antioxidative capacities can be used as a daily supplement for the prevention of oral Cd exposure. IMPORTANCE The heavy metal cadmium (Cd) is an environmental pollutant that causes adverse health effects in humans and animals. For the general population, food and drinking water are the main sources of Cd exposure due to the biomagnification of Cd within the food chain; therefore, the intestinal tract is the first organ that is susceptible to Cd

  3. Coexisted components of Salvia miltiorrhiza enhance intestinal absorption of cryptotanshinone via inhibition of the intestinal P-gp.

    PubMed

    Dai, Haixue; Li, Xiaorong; Li, Xiaoli; Bai, Lu; Li, Yuhang; Xue, Ming

    2012-11-15

    Cryptotanshinone, derived from the roots of Salvia miltiorrhiza Bge and Salvia przewalskii Maxim, is the major active component and possesses significant antibacterial, antidermatophytic, antioxidant, anti-inflammatory and anticancer activities. The objective of this study was to investigate the intestinal absorptive characteristics of cryptotanshinone as well as the absorptive behavior influenced by co-administration of the diterpenoid tanshinones and danxingfang using an in vitro everted rat gut sac model. The results showed a good linear correlation between cryptotanshinone of absorption and the incubation time from 10 to 70min. The concentration dependence showed that a non-linear correlation existed between the cryptotanshinone absorption and the concentration at 100 μg/ml. Coexisting diterpenoid tanshinones and danxingfang could significantly enhance the absorption of cryptotanshinone. Coexisting diterpenoid tanshinones and danxingfang, which influenced cryptotanshinone's absorption, manifested as similar to that of the P-glycoprotein inhibitor. The underlying mechanism of the improvement of oral bioavailability was proposed that coexisting diterpenoid tanshinones and danxingfang could decrease the efflux transport of cryptotanshinone by P-glycoprotein.

  4. Effect of carbachol on intestinal mucosal blood flow, activity of Na+-K+-ATPase, expression of aquaporin-1, and intestinal absorption rate during enteral resuscitation of burn shock in rats.

    PubMed

    Bao, Chengmei; Hu, Sen; Zhou, Guoyong; Tian, Yijun; Wu, Yan; Sheng, Zhiyong

    2010-01-01

    We investigated the effect of carbachol (CAR, a cholinergic agent) on intestinal mucosal blood flow (IMBF), activity of Na-K-ATPase, expression of aquaporin (AQP)-1, and intestinal absorption rate during enteral resuscitation of a 35%TBSA scald in rats with a glucose electrolyte solution (GES). One hundred male Wistar rats were randomly divided into five groups: sham scald (N group); scald without fluid resuscitation (S group); scald resuscitated with enteral GES alone (GES group); scald resuscitated with enteral CAR alone (CAR group); and scald resuscitated with enteral CAR plus GES (GES/CAR group). The rats were inflicted 35%TBSA third degree of scald injury on the back with boiling water (100 degrees C, 15 seconds) in all groups, except the sham scald group. A catheter was inserted into the proximal duodenum (5 cm distal to pylorus) and distal ileum (5 cm proximal to cecum), of each rats through laparotomy, thus a segment of intestine was virtually isolated to form a loop for inlet and outlet of introduced fluid. In N, GES, and GES/CAR groups, fluids were introduced 30 minutes after scald injury. The speed of fluid infusion was 4 ml/kg/1%TBSA for 4 hours. CAR (60 microg/kg) was injected into the intestinal lumen at 30-minute after injury in CAR and GES/CAR groups. At 2 and 4 hours after scald, intestinal absorption rate of water and Na, and IMBF were determined, respectively. Then, animals were killed, and specimens of intestinal tissue were obtained for the determination of the activity of Na-K-ATPase, hematoxylin-eosin coloring, and expression of AQP-1. The intestinal absorption rate was reduced markedly in GES group compared with sham scald group at 2 and 4 hours after scald, and absorption rate of small intestine in GES/CAR was significantly higher than that in GES group (P < .05). It was also found that there was significant decrease in IMBF, activity of Na-K-ATPase, and expression of AQP-1 in scald group compared with the sham group. However, in GES

  5. 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.

  6. Absorption of theophylline from the small and large intestine of the neonatal piglet.

    PubMed

    Murray, R D; Breech, L; Ailabouni, A; Zingerelli, J; Nahata, M C

    1993-01-01

    In this study, the newborn piglet model was used to assess theophylline absorption from various areas of the GI tract. 13 piglets, ages 9-14 days, had their intestines surgically exposed. Four segments of equal length (jejunum, ileum, right colon and left colon) were simultaneously perfused with a saline solution containing [3H]-polyethylene glycol 4000 to measure water shifts and theophylline at a total dose of 5 mg/kg, a typical neonatal dose. Absorption of theophylline, appearance in serum, and the effects of the drug on water and electrolyte movement in the intestinal segments were monitored. Serum concentrations of theophylline after an intravenous and oral dose were also studied in 2 piglets. The data showed excellent absorption of the drug from all intestinal segments studied (jejunum 0.97 +/- 0.16, ileum 0.7 +/- 0.13, right colon 0.7 +/- 0.13, and left colon 0.88 +/- 0.19 micrograms/cm/min), despite a concomitant secretion of sodium chloride and water. No statistical differences in absorptive capacity were seen among segments. The results suggest that as little as 100 cm of residual intestine could, theoretically, absorb a 5 mg dose of theophylline if presented slowly. These findings have ramifications for neonates who may receive theophylline orally or rectally.

  7. 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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

    PubMed

    Park, Mi-Young; Kwon, Hoon-Jeong; Sung, Mi-Kyung

    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 microM 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.

  9. Effect of abdominal surgery on the intestinal absorption of lipophilic drugs: possible role of the lymphatic transport.

    PubMed

    Gershkovich, Pavel; Itin, Constantin; Yacovan, Avihai; Amselem, Shimon; Hoffman, Amnon

    2009-06-01

    Although abdominal surgery is a routine procedure in clinical practice and in preclinical investigation, little is known regarding its effect on the intestinal absorption of drugs. The aim of this study was to investigate the effect of abdominal surgery on the intestinal absorption of highly lipophilic compounds with different absorption mechanisms following oral administration. The 2 compounds that were tested were biopharmaceutical classification system (BCS) class 2 model lipophilic cannabinoid derivatives, dexanabinol and PRS-211,220. Although dexanabinol is mostly absorbed via passive diffusion to the portal blood, PRS-211,220 is absorbed mostly via lymphatic transport. In this work, we compared the absorption of these compounds after abdominal surgery in rat with the absorption data obtained from naïve animals. The outcomes of this investigation showed that the abdominal surgery mostly affected the absorption process on the preenterocyte level, as indicated by the 2-fold increase in the extent of intestinal absorption of dexanabinol, which is a compound with a low degree of intestinal lymphatic transport. However, the lymphatic transport was not affected by the surgical procedure as evident by the absence of change in the extent of absorption of PRS-211,220, which is transported to the systemic circulation mainly by intestinal lymphatics. In conclusion, abdominal surgery can significantly affect the intestinal absorption of lipophilic drugs; however, intestinal lymphatic transport seems to be less affected by the abdominal surgery.

  10. [Effect of phosphate upon calcium intestinal absorption (author's transl)].

    PubMed

    Fournier, P; Dupuis, Y; Digaud, A; Fournier, A

    1976-11-01

    Adult rats receive 5 to 50 mM CaCl2 solutions in which glycerophosphate or sodium diacid phosphate may be added in variable quantity. These solutions are administered by gavage or in situ ligatured jejunal loop. The inhibition of calcium absorption dependent on simultaneously administered phosphate doses is well characterized: high for the lowest concentration, the inhibiting effect of phosphate doses decreases more and more reaching a limit from which phosphate supplementation has no effect. These observations discarding an intervention of phosphate by calcium insolubilization seem to demonstrate that the control supplied by phosphates on calcium absorption is of enzymatic character. Facts related to the respective effects of calcium and phosphates on the action of alkaline phosphatases lead to discuss a possible intervention of these enzymes upon calcium transfer.

  11. Net Intestinal Transport of Oxalate Reflects Passive Absorption and SLC26A6-mediated Secretion

    PubMed Central

    Knauf, Felix; Ko, Narae; Jiang, Zhirong; Robertson, William G.; Van Itallie, Christina M.; Anderson, James M.

    2011-01-01

    Mice lacking the oxalate transporter SLC26A6 develop hyperoxalemia, hyperoxaluria, and calcium-oxalate stones as a result of a defect in intestinal oxalate secretion, but what accounts for the absorptive oxalate flux remains unknown. We measured transepithelial absorption of [14C]oxalate simultaneously with the flux of [3H]mannitol, a marker of the paracellular pathway, across intestine from wild-type and Slc26a6-null mice. We used the anion transport inhibitor DIDS to investigate other members of the SLC26 family that may mediate transcellular oxalate absorption. Absorptive flux of oxalate in duodenum was similar to mannitol, insensitive to DIDS, and nonsaturable, indicating that it is predominantly passive and paracellular. In contrast, in wild-type mice, secretory flux of oxalate in duodenum exceeded that of mannitol, was sensitive to DIDS, and saturable, indicating transcellular secretion of oxalate. In Slc26a6-null mice, secretory flux of oxalate was similar to mannitol, and no net flux of oxalate occurred. Absorptive fluxes of both oxalate and mannitol varied in parallel in different segments of small and large intestine. In epithelial cell lines, modulation of the charge selectivity of the claudin-based pore pathway did not affect oxalate permeability, but knockdown of the tight-junction protein ZO-1 enhanced permeability to oxalate and mannitol in parallel. Moreover, formation of soluble complexes with cations did not affect oxalate absorption. In conclusion, absorptive oxalate flux occurs through the paracellular “leak” pathway, and net absorption of dietary oxalate depends on the relative balance between absorption and SLC26A6-dependent transcellular secretion. PMID:22021714

  12. Organic zinc absorption by the intestine of broilers in vivo.

    PubMed

    Yu, Yu; Lu, Lin; Li, Su-Fen; Zhang, Li-Yang; Luo, Xu-Gang

    2017-04-01

    In Expt 1, a Zn-unsupplemented basal diet (control) and the basal diet supplemented with one of four different Zn sources, including ZnSO4, Zn-amino acid chelate with a weak chelation strength (Zn-AA W), Zn-protein chelate with a moderate chelation strength (Zn-Pro M) and Zn-protein chelate with a strong chelation strength (Zn-Pro S) were fed to broiler chickens from days 14 to 28. On day 28, Zn content in plasma from the hepatic portal vein increased (P0·05) and Zn-AA W(P<0·04) were higher than those for ZnSO4. These findings indicate that organic Zn absorption (especially Zn-Pro S) in intact living broilers was more effective than that of inorganic Zn; organic Zn absorption in the ligated duodenal segment was a saturable carrier-mediated process similar to that of ZnSO4. Moreover, except for MT, there might be other Zn transporters involved in Zn absorption that are affected by different Zn sources.

  13. [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.

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

    PubMed

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

    2014-12-25

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

  15. Intestinal Absorption of Hemoglobin Iron-Heme Cleavage by Mucosal Heme Oxygenase

    PubMed Central

    Raffin, Steven B.; Woo, Choong H.; Roost, Kenneth T.; Price, David C.; Schmid, Rudi

    1974-01-01

    Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-α, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic 55Fe from 55Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined. PMID:4436436

  16. The origin of the glucose dependent increase in the potential difference across the tortoise small intestine

    PubMed Central

    Wright, E. M.

    1966-01-01

    1. Experiments were carried out to investigate the origin of the glucose dependent increase in the potential difference (p.d.) across the isolated intestinal mucosa of the tortoise. 2. In addition to glucose, galactose, α-methyl glucoside, 3-0-methyl glucopyranose and sucrose also increased the transepithelial potential difference. There was no increase with either fructose or mannose. 3. The use of micro-electrodes demonstrated that the change in the p.d. due to the presence of glucose was wholly accounted for by the increase in the p.d. across the serosal face of the epithelial cells. 4. Diffusion potentials were produced across the isolated mucosa by varying the ionic composition of either the mucosal or serosal fluids. However, there was no reduction of the glucose dependent increase in the p.d. when the ionic concentration gradients across the serosal face of the cell were reversed. 5. These results suggest that the increase in the p.d. associated with the active transfer of sugars across the small intestine was due to the presence of an electrogenic ion pump at the serosal face of the epithelial cell. PMID:16992234

  17. Phenolics from Whole Grain Oat Products as Modifiers of Starch Digestion and Intestinal Glucose Transport.

    PubMed

    Li, Min; Koecher, Katie; Hansen, Laura; Ferruzzi, Mario G

    2017-08-16

    Four oat varieties and three product forms (porridge, cereal, and snack bar) were assessed to determine the impact of oat phenolics on starch digestibility and intestinal glucose transport. α-Amylase activity was enhanced by 20 GAE μM (gallic acid equivalent) of phenolics extracted from oat (96.7-118%, p < 0.05), while it was modestly inhibited at 500 GAE μM (83.0-95.4%). Maltose hydrolysis was reduced (49.6-82.4%, p < 0.05), albeit with high IC50 values (500-940 GAE μM). Free and bound oat phenolic extracts dose-dependently attenuated transport of d-glucose-1,2,3,4,5,6,6-d7 by Caco-2 monolayers over 60 min. Oat foods were then subjected to a coupled in vitro digestion/Caco-2 intestinal cell model to determine relevance to whole food systems. Digestive release of glucose was similar among products; however, glucose transport was significantly reduced from digesta of GMI 423 porridge and puffed cereal by 34% ± 12% and 20% ± 10% (p < 0.05) at 60 min. Results suggest phenolics might be a factor modulating glycemic response of oat products.

  18. Enhanced intestinal absorption of daidzein by borneol/menthol eutectic mixture and microemulsion.

    PubMed

    Shen, Qi; Li, Xi; Li, Wenji; Zhao, Xinyi

    2011-12-01

    In the present study, the effect of a borneol/menthol eutectic mixture (25:75) and microemulsion on the absorption of daidzein in rat intestinal membrane was evaluated. The microemulsion formulation was composed of ethyl oleate (oil), Cremophor RH40 (surfactant), PEG400 (co-surfactant), and water. The borneol/menthol eutectic mixture and its microemulsion were found to enhance the intestinal absorption of daidzein in vitro. A diffusion chamber system with isolated rat intestinal membranes was used. In contrast, verapamil (0.3 mM), a typical P-glycoprotein inhibitor, showed no effect on the absorption of daidzein by this system. A pharmacokinetic study was conducted in rats. After oral administration of daidzein at a dose of 10 mg/kg in the form of either borneol/menthol eutectic mixtures or suspension, the relative bioavailability of borneol/menthol eutectic mixtures and microemulsion was enhanced by about 1.5- and 3.65-fold, respectively, compared with a daidzein suspension. In conclusion, a borneol/menthol eutectic mixture can enhance the absorption of daidzein, although the mechanism of absorption enhancement is still unclear.

  19. Rapid Upregulation of Sodium-Glucose Transporter SGLT1 in Response to Intestinal Sweet Taste Stimulation

    PubMed Central

    Stearns, Adam T.; Balakrishnan, Anita; Rhoads, David B.; Tavakkolizadeh, Ali

    2014-01-01

    Objective We set out to examine the short-term regulation of the intestinal sodium/glucose cotransporter SGLT1 by its substrate glucose and sweet taste analogs. Summary Background Data Intestinal SGLT1 is a putative target for antidiabetic therapy; however, its physiological regulation is incompletely understood, limiting its application as a pharmacological target. While it is clearly regulated by dietary composition over a period of days, its short-term regulation by nutrients is unknown. Methods Sprague-Dawley rats were anesthetized, and the duodenum cannulated. D-glucose, D-fructose, saccharin, D-mannitol, and water were infused for 3 hours, before harvest of proximal jejunum for SGLT1 analysis with Western blotting and quantitative polymerase chain reaction. In further experiments, the receptor region was identified by D-glucose infusion of isolated regions. Lastly, the vagus was de-afferented with capsaicin, and 5HT3-receptor activation of vagal afferents inhibited using ondansetron, before repeating experiments using water or D-glucose infusion. Results Infusion of D-glucose led to 2.9-fold up-regulation in SGLT1 compared with water or iso-osmotic D-mannitol; this effect was replicated by D-fructose or saccharin. This response was strongest following isolated infusions of duodenum and proximal jejunum, with a blunted effect distally; topography matched the expression profile of sweet taste receptor T1R2/T1R3. The reflex was abolished by capsaicin pretreatment, and blunted by ondansetron. Conclusions The agonist response implicates the luminal-based sweet-taste receptor T1R2/T1R3, with the reflex apparently involving vagal afferents. The proximal nature of the sensor coincides with the excluded biliopancreatic limb in Roux-en-Y gastric bypass, and this may provide a novel explanation for the antidiabetic effect of this procedure. PMID:20395849

  20. Absorption of D-[{sup 14}C]-glucose and D-[{sup 3}H]-mannose in everted rat jejunum

    SciTech Connect

    Wagner, B.; Galey, W.R. Jr.

    1997-12-01

    Radiolabeled elements are useful in measuring physiologic processes in mammalian tissues. Absorption of D-[{sup 14}C]-glucose is often used as a marker for active transport by the sodium-dependent transmembrane glucose/galactose carrier, SGLT1, present in epithelial tissues. Also, D-[{sup 3}H]-mannose monitors the flux of a passively absorbed hexose through the intestinal wall. Many gastrointestinal absorption studies have employed the everted gut sac method developed by Wilson and Wiseman in 1954. Phloridzin is a glycoside derived from apple trees and an effective inhibitor of the sodium-dependent glucose carrier. It was hypothesized that a kinetic study of radiolabeled hexoses could be successfully applied to a modification of this method and assayed by an inhibitory effect of phloridzin on D-[{sup 14}C]-glucose influx into everted rat jejunum and that glycosides transported by the sodium-dependent glucose transporter would have a similar inhibitory effect on D-[{sup 14}C]-glucose influx.

  1. In vivo regulation of intestinal absorption of amino acids by leptin.

    PubMed

    Fanjul, Carmen; Barrenetxe, Jaione; De Pablo-Maiso, Lorena; Lostao, María Pilar

    2015-01-01

    Leptin is secreted by the gastric mucosa and is able to reach the intestinal lumen and bind to its receptors located in the apical membranes of enterocytes. We have previously demonstrated that apical leptin inhibits uptake of amino acids in rat intestine in vitro and in Caco-2 cells. The aim of the present work was to investigate the effect of leptin on absorption of amino acids using in vivo techniques, which generate situations closer to physiological conditions. In vivo intestinal absorption of amino acids in rats was measured by isolating a jejunal loop and using the single-pass perfusion system. Disappearance of glutamine (Gln), proline (Pro), and β-alanine (β-Ala) from the perfusate, in the absence or presence of leptin, was measured using a radioactivity method. Luminal leptin (25 nM) inhibited the absorption of 2 mM Pro, 5 mM β-Ala, and 5 mM Gln by approximately 45% after 5-15 min; the effect remained constant until the end of the experiment (80 min) and was rapidly and completely reversed when leptin was removed from the perfusion medium. Moreover, leptin was able to regulate the absorption of galactose and Gln in the same animal, indicating a direct action of the hormone on the specific transporters implicated in the uptake of each nutrient. The results of the present work indicate that luminal leptin decreases absorption of amino acids in vivo in a short-term manner and in a reversible way. These results, together with our previous findings, make it evident that leptin can be considered as a hormone which provides the intestine with a control mechanism to handle absorption of nutrients.

  2. 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.

  3. 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

  4. Studies on the Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Waldron-Edward, Deirdre; Paul, T. M.; Skoryna, Stanley C.

    1964-01-01

    A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to be available to the body. Studies were carried out by measuring bone uptake of Sr89 and Ca45 when various amounts of sodium alginate were fed with the diet. Long-term studies were made in which two different levels of radioactivity were used, to determine the pattern of Sr89 deposition with continuous intake of binding agent. It was found that administration of sodium alginate as a jelly overcomes the problem of constipation and effectively reduces Sr89 uptake, up to 83%. This fact represents a significant finding with respect to the use of the compound in human subjects. Addition of sodium alginate to drinking water is effective with low levels of Sr89 intake. This naturally occurring water-soluble macromolecular substance possesses several advantages in use for the suppression of absorption of radioactive strontium when compared with synthetic ion exchange resins: there is no disturbance of electrolyte balance; efficiency is not reduced by treatment over a prolonged period of time; and finally, the product is palatable. PMID:14222668

  5. Erythrocyte membrane nanoparticles improve the intestinal absorption of paclitaxel.

    PubMed

    Jiang, Xing; Wang, Kaikai; Zhou, Zaigang; Zhang, Yifan; Sha, Huizi; Xu, Qiuping; Wu, Jie; Wang, Juan; Wu, Jinhui; Hu, Yiqiao; Liu, Baorui

    2017-06-24

    Paclitaxel (PTX) is a cytotoxic chemotherapy drug with encouraging activity in human malignancies. However, free PTX has a very low oral bioavailability due to its low aqueous solubility and the gastrointestinal drug barrier. In order to overcome this obstacle, we have designed erythrocyte membrane nanoparticles (EMNP) using sonication method. The permeability of PTX by EMNP was 3.5-fold (Papp = 0.425 nm/s) and 16.2-fold (Papp = 394.1 nm/s) higher than free PTX in MDCK-MDR1 cell monolayers and intestinal mucosal tissue, respectively. The in vivo pharmacokinetics indicated that the AUC0-t (μg/mL·h) and Cmax (μg/mL) of EMNP were 14.2-fold and 6.0-fold higher than that of free PTX, respectively. In summary, the EMNP appears to be a promising nanoformulation to enhance the oral bioavailability of insoluble and poorly permeable drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. [Determination method of muscone in rat intestinal perfusate by GC-MS/MS and its intestinal absorption kinetic characteristics in rats].

    PubMed

    Zou, Liang; Lin, Junzhi; Wang, Zhanguo; Xu, Lijia; Wang, Ping; Zhao, Gang; Luo, Jieying

    2012-08-01

    To establish the method for determining muscone in rat intestinal perfusate by GC-MS/MS and study its intestinal absorption kinetic characteristics in rats. The GC-MS/MS method was used to determine the content of muscone in rat intestinal circulation fluid. In situ intestinal circulation perfusion was adopted to study absorption kinetics of muscone in rats. Muscone was proved to be well absorbed in each section of small intestine. Its absorption rate constants (Ka) and the absorption rate (A) in the rat intestine showed duodenum > jejunum (P < 0.05) , duodenum > ileum (P < 0.01). Its Ka, A and t1/2 in rat small intestine was 0.990 h(-1) , 43.58% and 0.705h, respectively. Muscone was well absorbed in each intestinal section, with duodenum better than jejunum (Ka, T1/2, P < 0.05) significantly better than ileum (Ka, T1/2, P < 0.01; A, P < 0.05). There is no obvious statistical difference between jejunum and ileum.

  7. Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats.

    PubMed

    Zhang, Hailong; Huang, Xiaoyan; Zhang, Yongjing; Gao, Yang

    2017-03-01

    Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic. To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats. Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively. HP-β-CD-PEI polymers, especially HP-β-CD-PEI1800, demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects. HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

  8. 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

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

    PubMed

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

    2013-08-20

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

  10. Intestinal absorption of amino acids and peptides in Hartnup disorder.

    PubMed

    Leonard, J V; Marrs, T C; Addison, J M; Burston, D; Clegg, K M; Lloyd, J K; Matthews, D M; Seakins, J W

    1976-04-01

    Absorption of free and peptide-bound amino acids was investigated in a girl with Hartnup disorder aged 26 months. Plasma levels of amino acids were followed after oral administration of (1) an amino acid mixture simulating casein and (2) an equivalent dose of a partial enzymic hydrolysate of casein containing oligopeptides in addition to free amino acids. The results suggested that many neutral amino acids were poorly absorbed when given in the free form, but much more readily absorbed when given as peptides. Unexpectedly, the results also suggested that glutamic acid was poorly absorbed when given in the free form. The results obtained with threonine could not be interpreted. There was an increased renal clearance of many neutral amino acids, including glycine, but clearance of proline was not increased. Most amino acids with an increased renal clearance also appeared to be poorly absorbed when given by mouth in the free form.

  11. Studies of Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Skoryna, Stanley C.; Paul, T. M.; Waldron-Edward, Deirdre

    1965-01-01

    A method is reported which permits selective suppression of absorption of radioactive strontium from ingested food material, allowing calcium to be available to the body. Studies were carried out on the inhibitory effect of various amounts of sodium alginate and the dose-response relationship of Sr89 and bone uptake. The results obtained indicated that under laboratory conditions sodium alginate effectively reduces Sr89 uptake in a constant proportion. This effect was observed at the three levels of administration of 1.4%, 12% and 24% of sodium alginate. The linear relationship between the dosage of the radioisotope and the bone uptake in the presence of sodium alginate suggests that the same proportion is maintained at the lower levels of intake of radioactive strontium. Previous studies with small constant doses of sodium alginate were extended in rats to a period corresponding approximately to three years of human life span. Low doses were sufficient to reduce appreciably bone uptake of radiostrontium. PMID:14341649

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-20

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2(-/-)) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed

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

    2013-06-01

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

  15. Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats.

    PubMed

    Sinko, P J; Balimane, P V

    1998-05-01

    The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester prodrug of acyclovir, was investigated in rats using an in situ intestinal perfusion technique. VACV demonstrates an oral bioavailability that is three to five time greater than acyclovir, concentration dependent, and saturable in humans. Homogenate and perfused buffer stability results demonstrated that VACV was increasingly unstable with increasing pH. VACV was converted to ACV in a concentration dependent manner during a single pass through the intestinal segment. Perfusions were performed at 37 degrees C, pH 6.5, and under iso-osmotic conditions (290 +/- 10 mOsm L-1). Intestinal outlet concentrations were corrected for VACV that was converted to ACV during the perfusion. The effective dimensionless intestinal permeability (P*e) of VACV was concentration dependent, saturable (intrinsic Km = 1.2 +/- 0.7 mM), and significantly reduced (p < 0.05) in the presence of peptide analogues (amoxicillin, ampicillin, cefadroxil, and cephradine), by the organic anion, p-amino hippuric acid and by the organic cation quinine. VACV transport was not inhibited by classical nucleoside competitive substrates or inhibitors or by valine. These results suggest that H(+)-oligopeptide, H(+)-organic cation, and organic anion transporters are involved in the small intestinal uptake of VACV. The permeability of VACV in the colon was very low, indicating that VACV is predominantly absorbed from the small intestine. VACV P*e was not altered in the presence of glucose-induced convective fluid flow, suggesting that carrier-mediated, transcellular uptake is the predominant absorption pathway of VACV in rat small intestine. Based on these results, the oral bioavailability of VACV appears to be significantly influenced by the preabsorptive conversion of VACV to the poorly absorbed ACV, by the involvement of multiple transporters in VACV small-intestinal uptake, and by the low permeability of VACV in the colon.

  16. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome?

    PubMed

    Luo, Menghua; Fernández-Estívariz, Concepción; Manatunga, Amita K; Bazargan, Niloofar; Gu, Li H; Jones, Dean P; Klapproth, Jan-Michael; Sitaraman, Shanthi V; Leader, Lorraine M; Galloway, John R; Ziegler, Thomas R

    2007-01-01

    Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared

  17. Intestinal brush border membrane Na+/glucose cotransporter functions in situ as a homotetramer

    SciTech Connect

    Stevens, B.R.; Fernandez, A.; Hirayama, B.; Wright, E.M.; Kempner, E.S. )

    1990-02-01

    The functional unit molecular size of the intestinal brush border membrane-bound Na+/glucose cotransporter was determined by radiation inactivation. Purified brush border membrane vesicles preserved in cryoprotectant buffer were irradiated (-135 degrees C) with high-energy electrons from a 13-MeV (1 eV = 1.602 x 10(-19) J) linear accelerator at doses from 0 to 70 Mrad (1 rad = 0.01 Gy). After each dose, the cotransporter was investigated with respect to (i) Na(+)-dependent transport activity and (ii) immunologic blot analysis with antibodies against the cloned rabbit intestinal cotransporter. Increasing radiation decreased the maximal Na(+)-dependent cotransporter activity Jmax without affecting apparent Km. The size of the transporting functional unit was 290 +/- 5 kDa. Immunologic blot analysis of brush border membranes gave a single band of Mr 70,000, which decreased in intensity with increased radiation dose and gave a target size of 66 +/- 11 kDa. We conclude that activity of the intestinal Na+/glucose cotransporter in situ in the brush border membrane requires the simultaneous presence of four intact, independent, identical subunits arranged as a homotetramer.

  18. 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.

  19. Intestinal absorption of strontium chloride in healthy volunteers: pharmacokinetics and reproducibility

    PubMed Central

    SIPS, A. J. A. M.; van der VIJGH, W. J. F.; BARTO, R.; NETELENBOS, J. C.

    1996-01-01

    1The absorption kinetics of orally administered strontium chloride and its reproducibility were investigated in healthy volunteers after administering strontium either under fasting conditions (study I, n=8) or in combination with a standardized meal (study II, n=8). Each subject received strontium orally at day 0, 14, and 28 and intravenously at day 42. The study was performed as part of a project in which a simple clinical test for measuring intestinal calcium absorption is being developed, based on the use of stable strontium as a marker. 2Plasma strontium concentration–time curves were analysed by noncompartment analysis and a four compartment disposition model. Within a volunteer each oral curve was fitted simultaneously with the intravenous curve, by which means a two segment model for absorption was revealed. 3Mean absolute bioavailability of strontium was 25% without a meal and 19% with a meal, whereas the intraindividual variation was 24% and 20%, respectively. 4Various limited sampling absorption parameters were determined in order to select a potential test parameter for measuring intestinal calcium absorption using strontium as a marker. Fractional absorption at 4 h (Fc240), obtained after co-ingestion of strontium with a meal, appeared to be the best test parameter, because it represented bioavailability well (r=0.90). PMID:8799520

  20. 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.

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

    PubMed

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

    2015-09-08

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

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

    PubMed

    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 14C-triolein marker remained proportional to the load up to 2,359 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 14C-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.

  3. 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

  4. 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.

  5. Calcium and glucose uptake in rat small intestinal brush-border membrane vesicles. Modulation by exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3.

    PubMed

    Braun, H J; Birkenhäger, J C; De Jonge, H R

    1984-07-11

    The effect of exogenous hypercortisolism and 1,25-dihydroxyvitamin D-3 on small-intestinal calcium and glucose transport in the rat was studied at the level of brush-border membrane vesicles generated from isolated villous cells by a freeze-thaw procedure. At 5 X 10(-5) M extravesicular calcium, initial uptake rates in vesicles prepared from triamcinolone-treated adult rats were decreased by 30% after 5 days. Since calcium ionophore A23187 virtually abolished the difference in calcium uptake, triamcinolone appeared to affect calcium channel density or activity rather than intravesicular binding capacity. Kinetic analysis showed that a decrease in Vmax of a saturable calcium transport system could entirely account for the diminished rate of vesicular calcium uptake. Calcium transport rates could be partially restored by in vivo administration of 1,25-dihydroxyvitamin D-3 at a dosage which did not affect vesicular calcium uptake in control animals. Conversely, sodium-driven glucose accumulation in brush-border vesicles from triamcinolone-treated rats was stimulated by 50-70% after 36 h and appeared insensitive to vitamin D. A specific triamcinolone action on the glucose carrier itself rather than on the driving force of the sodium gradient was indicated by (i) a similar stimulation of glucose transport under equilibrium exchange conditions and (ii) an opposite effect of triamcinolone on sodium-driven alanine transport. The triamcinolone-induced changes in calcium and glucose uptake were not accompanied by a gross alteration of membrane integrity in vitro or by major alterations in vesicular protein composition, intravesicular glucose space and sucrase or alkaline phosphatase activity. The modification of vesicular transport properties is discussed in relation to the vitamin D-antagonized inhibition of intestinal calcium uptake and the stimulation of glucose absorption in response to supraphysiologic amounts of glucocorticoids observed in intact epithelium.

  6. 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.

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

    PubMed

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

    2015-02-01

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

  8. 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

  9. Studies on Inhibition of Intestinal Absorption of Radioactive Strontium

    PubMed Central

    Paul, T. M.; Edward, Deirdre Waldron; Skoryna, Stanley C.

    1964-01-01

    A method is reported that enables selective suppression of absorption of radioactive strontium from ingested food material, permitting calcium to remain available to the body. Studies were carried out by measuring blood levels and bone uptake of Sr89 and Ca45 at different time intervals after orogastric intubation of rats. The addition of sodium alginate, derived from brown marine algae, to the radioactive isotopes increased the overall physiological discrimination against strontium by amounts up to 60% after 24 hours. This discrimination was further increased by feeding sodium alginate mixed with standard diet in the proportions of 20:80 and 30:70. The observed ratio was reduced by administration of sodium alginate from 0.25 to 0.09. Determination of the limiting dosage in rats is restricted to the amounts which rats will consume. In the event of an inadvertent release of radioactive strontium, human subjects probably could increase their intake of alginate at will, permitting a greater effectiveness of sodium alginate than could be obtained in experimental animals. PMID:14176062

  10. 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.

  11. The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.

    PubMed

    Chan, Kelvin; Liu, Zhong Qiu; Jiang, Zhi Hong; Zhou, Hua; Wong, Yuen Fan; Xu, Hong-Xi; Liu, Liang

    2006-02-20

    Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.

  12. Intestinal absorptive transport of Genkwanin from Flos genkwa using a single-pass intestinal perfusion rat model.

    PubMed

    Jiang, Cui-Ping; He, Xin; Yang, Xiao-Lin; Zhang, Su-Li; Li, Hui; Song, Zi-Jing; Zhang, Chun-Feng; Yang, Zhong-Lin; Li, Ping

    2014-01-01

    To investigate the absorptive transport behavior of genkwanin and the beneficial effects of monoterpene enhancers with different functional groups, the single-pass intestinal perfusion (SPIP) of rats was used. The results showed that genkwanin was segmentally-dependent and the best absorptive site was the duodenum. The effective permeability coefficient (P eff ) was 1.97 × 10(-4) cm/s and the absorption rate constant (Ka) was 0.62 × 10(-2) s(-1). Transepithelial transportation descended with increasing concentrations of genkwanin. This was a 1.4-fold increase in P eff by probenecid, whereas a 1.4-fold or 1.6-fold decrease was observed by verapamil and pantoprazole, respectively. Furthermore, among the absorption enhancers, the enhancement with carbonyl (camphor and menthone) was higher than that with hydroxyl (borneol and menthol). The concentration-independent permeability and enhancement by coperfusion of probenecid indicated that genkwanin was transported by both passive diffusion and multidrug resistance protein (MDR)-mediated efflux mechanisms.

  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. 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.

  15. Effect of Inhibition of Intestinal Cholesterol Absorption on the Prevention of Cholesterol Gallstone Formation.

    PubMed

    Portincasa, Piero; Wang, David Q-H

    2017-01-01

    Cholesterol cholelithiasis is a multifactorial hepatobiliary disease. Interactions between genetic and environmental factors play a critical role in biliary cholesterol homeostasis and its imbalance enhances cholelithogenesis. In patients developing symptoms or complications of gallstone disease, laparoscopic cholecystectomy is recommended for treatment of gallstones. In a subgroup of patients with small, radiolucent pure cholesterol gallstones, the hydrophilic bile acid, ursodeoxycholic acid (UDCA) is still considered the only pharmacological therapy able to induce oral litholysis. Identifying novel and effective pharmacological therapies is being investigated. We propose that the specific intestinal Niemann-Pick C1-like 1 protein inhibitor ezetimibe is a potential agent for preventing gallstone formation by reducing bioavailability of intestine- derived cholesterol to the liver for biliary secretion and desaturating bile through the inhibition of intestinal absorption of cholesterol. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Very low density lipoproteins in intestinal lymph: role in triglyceride and cholesterol transport during fat absorption

    PubMed Central

    Ockner, Robert K.; Hughes, Faith B.; Isselbacher, Kurt J.

    1969-01-01

    The role of nonchylomicron very low density lipoproteins (VLDL, Sf 20-400) in the transport of triglyceride and cholesterol was studied during lipid absorption. Various long chain fatty acids were infused intraduodenally in the form of mixed fatty acid—mono-olein-taurocholate micelles; control animals received saline or taurocholate. As compared with controls, all fatty acids (palmitic, oleic, linoleic) resulted in significant increases in chylomicron (Sf > 400) triglyceride. In addition, palmitic acid resulted in a twofold increase in VLDL triglyceride, whereas with the absorption of oleic or linoleic acid VLDL triglyceride did not change significantly. Differences in triglyceride fatty acid composition between chylomicrons and VLDL were observed during lipid absorption. Although the absolute amount of endogenous cholesterol in intestinal lymph was not significantly affected by lipid absorption under these conditions, its lipoprotein distribution differed substantially among the lipid-infused groups. During palmitate absorption, VLDL cholesterol was similar to that in the taurocholate-infused controls, and was equal to chylomicron cholesterol. In contrast, during oleate and linoleate absorption the VLDL cholesterol fell markedly, and was less than half of the chylomicron cholesterol in these groups. The half-time of plasma survival of VLDL cholesterol-14C was found to be twice that of chylomicron cholesterol-14C. These studies demonstrate that dietary long chain fatty acids differ significantly in their effects upon the transport of triglyceride and cholesterol by lipoproteins of rat intestinal lymph. These findings, together with the observed differences in rates of removal of chylomicrons and VLDL from plasma, suggest that variations in lipoprotein production at the intestinal level may be reflected in differences in the subsequent metabolism of absorbed dietary and endogenous lipids. PMID:5355348

  17. 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. Copyright © 2012 John Wiley & Sons, Ltd.

  18. 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.

  19. Iron regulatory proteins control a mucosal block to intestinal iron absorption.

    PubMed

    Galy, Bruno; Ferring-Appel, Dunja; Becker, Christiane; Gretz, Norbert; Gröne, Hermann-Josef; Schümann, Klaus; Hentze, Matthias W

    2013-03-28

    Mammalian iron metabolism is regulated systemically by the hormone hepcidin and cellularly by iron regulatory proteins (IRPs) that orchestrate a posttranscriptional regulatory network. Through ligand-inducible genetic ablation of both IRPs in the gut epithelium of adult mice, we demonstrate that IRP deficiency impairs iron absorption and promotes mucosal iron retention via a ferritin-mediated "mucosal block." We show that IRP deficiency does not interfere with intestinal sensing of body iron loading and erythropoietic iron need, but rather alters the basal expression of the iron-absorption machinery. IRPs thus secure sufficient iron transport across absorptive enterocytes by restricting the ferritin "mucosal block" and define a basal set point for iron absorption upon which IRP-independent systemic regulatory inputs are overlaid.

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

    USGS Publications Warehouse

    Serafin, J.A.

    1984-01-01

    1. 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.2. Bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards.3. Mallards absorbed less dieldrin and mercury than black-crowned night-herons.4. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards.5. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  3. Calcium solubility, intestinal sojourn time and paracellular permeability codetermine passive calcium absorption in rats.

    PubMed

    Duflos, C; Bellaton, C; Pansu, D; Bronner, F

    1995-09-01

    To investigate the nonsaturable, paracellular pathway of intestinal Ca absorption, the luminal contents of 12-cm segments of the intestine of 8-wk-old male Sprague-Dawley rats were analyzed for pH, sojourn time and soluble and insoluble Ca over a 24-h period. The rats had been fed one of two high Ca diets for 2 wk: 1.5% Ca (diet group 3a) and 3.1% (diet group 5a). The pH of the small intestine increased from < 6.6 to > 8.0 from duodenum to ileum; transit time increased from 2.5 min in the duodenum to 58 min in the distal ileum, with the entire ileum accounting on the average for 74% of the transit time of 3 h. The amount of Ca solubilized throughout the intestine was 32 +/- 3.3 mumol in diet group 3a and 53 +/- 5.3 mumol in diet group 5a, i.e., 2.7% and 2.0% of the total luminal Ca. Because absorption by diet group 3a was 1.45 +/- 0.23 mmol/d and that by diet group 5a was 2.50 +/- 0.18 mmol/d, the amounts absorbed were 45.3 and 47.1 times greater than present in the lumen in soluble form at any one time. Thus, over a 24-h period, an average of 3.2% (46.2/1440) of the soluble Ca present in the lumen at any time was absorbed per min. Calculations involving the gradient between luminal and plasma Ca show that the rate of Ca diffusion from lumen to blood is < 2% of what it would be if the paracellular path were unrestricted. Thus, intestinal sojourn time, Ca solubility and mucosal permeability to Ca are factors that determine the rate of passive Ca absorption.

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

    PubMed Central

    Renaud, Helen J.; Klaassen, Curtis D.

    2016-01-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [3H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [3H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum–fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance. PMID:26744253

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

    PubMed

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

    2016-03-01

    There is wide variation in how patients respond to therapeutics. Factors that contribute to pharmacokinetic variations include disease, genetics, drugs, age, and diet. The purpose of this study was to determine the effect of calorie restriction on the expression of Abcb1a in the intestine and whether calorie restriction can alter the absorption of an Abcb1a substrate (i.e., digoxin) in mice. Ten-week-old C57BL/6 mice were given either an ad libitum diet or a 25% calorie-restricted diet for 3 weeks. To determine digoxin absorption, mice were administered [(3)H]-labeled digoxin by oral gavage. Blood and intestine with contents were collected at 1, 2, 4, and 12 hours after digoxin administration. Concentrations of [(3)H]-digoxin in plasma and tissues were determined by liquid scintillation. Calorie restriction decreased plasma digoxin concentrations (about 60%) at 1, 2, and 4 hours after administration. Additionally, digoxin concentrations in the small intestine of calorie-restricted mice were elevated at 4 and 12 hours after administration. Furthermore, calorie restriction increased Abcb1a transcripts in the duodenum (4.5-fold) and jejunum (12.5-fold). To confirm a role of Abcb1a in the altered digoxin pharmacokinetics induced by calorie restriction, the experiment was repeated in Abcb1a/b-null mice 4 hours after drug administration. No difference in intestine or plasma digoxin concentrations were observed between ad libitum-fed and calorie-restricted Abcb1a/b-null mice. Thus, these findings support the hypothesis that calorie restriction increases intestinal Abcb1a expression, leading to decreased absorption of digoxin in mice. Because Abcb1a transports a wide variety of therapeutics, these results may be of important clinical significance. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

    PubMed Central

    Subramanya, Sandeep B.; Subramanian, Veedamali S.; Kumar, Jeyan S.; Hoiness, Robert

    2011-01-01

    The water-soluble vitamin biotin is essential for normal cellular functions and its deficiency leads to a variety of clinical abnormalities. Mammals obtain biotin from exogenous sources via intestinal absorption, a process mediated by the sodium-dependent multivitamin transporter (SMVT). Chronic alcohol use in humans is associated with a significant reduction in plasma biotin levels, and animal studies have shown inhibition in intestinal biotin absorption by chronic alcohol feeding. Little, however, is known about the cellular and molecular mechanisms involved in the inhibition in intestinal biotin transport by chronic alcohol use. These mechanisms were investigated in this study by using rats and transgenic mice carrying the human full-length SLC5A6 5′-regulatory region chronically fed alcohol liquid diets; human intestinal epithelial Caco-2 cells chronically exposed to alcohol were also used as models. The results showed chronic alcohol feeding of rats to lead to a significant inhibition in carrier-mediated biotin transport events across jejunal brush border and basolateral membrane domains. This inhibition was associated with a significant reduction in level of expression of the SMVT protein, mRNA, and heterogenous nuclear RNA. Chronic alcohol feeding also inhibited carrier-mediated biotin uptake in rat colon. Studies with transgenic mice confirmed the above findings and further showed chronic alcohol feeding significantly inhibited the activity of SLC5A6 5′-regulatory region. Finally, chronic exposure of Caco-2 cells to alcohol led to a significant decrease in the activity of both promoters P1 and P2 of the human SLC5A6 gene. These studies identify for the first time the cellular and molecular parameters of the intestinal biotin absorptive processes that are affected by chronic alcohol feeding. PMID:21148397

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

    PubMed

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

    2011-03-01

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

  8. Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease

    PubMed Central

    Navab, F.; Asatoor, A. M.

    1970-01-01

    A severely affected case of Hartnup disease is reported, where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, β-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal. ImagesFig. 5Fig. 6 PMID:4246731

  9. Studies on intestinal absorption of amino acids and a dipeptide in a case of Hartnup disease.

    PubMed

    Navab, F; Asatoor, A M

    1970-05-01

    A severely affected case of Hartnup disease is reported, where the patient responded rapidly to nicotinamide. This supports the view that all the clinical features, except reduced stature from general nutritional defect, are secondary to tryptophan and nicotinamide deficiency rather than to an unknown toxic factor. Severe malabsorption of both tryptophan and phenylalanine was demonstrated. The dipeptide carnosine was absorbed normally whereas when the two constituent amino acids, beta-alanine and L-histidine, were ingested, absorption of the former was normal but that of the latter was grossly defective. The suggestion is advanced that in cases of Hartnup disease protein nutrition is maintained by intestinal uptake of amino acids as oligopeptides rather than as free amino acids. By contrast, both modes of absorption are probably important in normal subjects. Radiology of the small intestine is abnormal in Hartnup disease when a large amount of protein is admixed with the barium meal.

  10. Influence of dietary fat on the intestinal absorption of lipophilic compounds in goldfish (Carassius auratus).

    PubMed

    Sharifi, M; Connell, W D; Gabric, A

    1997-12-01

    Dietary uptake of a mixture of pp'DDT and four chlorobenzenes from diets with different lipid contents was measured in goldfish (Carassius auratus) in order to investigate the mechanism of intestinal absorption of organic compounds. The results of the experiments suggest that intestinal absorption is basically controlled by chemical diffusion rather than lipid coassimilation. The extent of dietary uptake as indicated by biomagnification factor was strongly correlated with the chemical log Kow, indicating that uptake of the chemicals from the gastrointestinal fluid is similar to the uptake from other aqueous environments and lipid content of the food in the range used in these experiments (2.9-10.9%) could not influence the uptake of lipophilic chemicals.

  11. Olive oil improves the intestinal absorption and bioavailability of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Mamatha, Bangera Sheshappa; Baskaran, V

    2014-02-01

    To investigate the influence of olive (OO), groundnut (GNO), soybean (SBO), sunflower (SFO), rice bran (RBO), corn (CO), palm (PO) oil or mixed micelle (control) on absorption kinetics and bioavailability of lutein in lutein-deficient mice. Additional aim was to correlate the activity of intestinal triacylglycerol lipase with intestinal and plasma lutein levels. After induction of lutein deficiency, mice (n = 165) were divided into eight groups (OO, SFO, GNO, RBO, PO, CO, SBO and control; n = 20/group) and the remaining (n = 5) were used as baseline (0 h). Groups were further divided into four subgroups (n = 5/subgroup) and were intubated with lutein (200 μM) dispersed in different vegetable oils. Plasma and tissue (intestine, liver and eyes), lutein, triglycerides, intestinal triacylglycerol lipases and fatty acid profile of plasma and tissues were measured at different time intervals. The percentage area under the curve value for plasma lutein in OO and GNO was higher by 41.8 and 5.1 %, while it was lower in other groups (18.2-53.3 %), when compared to control. Similarly, the percentage area under the curve for eye lutein in OO and GNO groups was higher by 35.2 and 4.8 %, whereas in other groups it was lower (5.4-69 %) than in control. Results show that olive oil facilitates the lutein absorption more compared to other vegetable oils, which may be due to the difference in fatty acid composition and higher activity of intestinal triacylglycerol lipase. Dietary olive oil rich in oleic acid improves the bioavailability and accumulation of lutein in lutein-deficient mice by modifying the intestinal triacylglycerol lipase activity.

  12. Influence of phosvitin and calcium gluconate concentration on permeation and intestinal absorption of calcium ions.

    PubMed

    Dolińska, Barbara; Łopata, Katarzyna; Mikulska, Agnieszka; Leszczyńska, Lucyna; Ryszka, Florian

    2012-06-01

    The effect of egg yolk phosvitin on the permeation and absorption of calcium was investigated in vitro in relation to calcium gluconate concentration. Obtained results indicate that phosvitin significantly reduces the intestinal calcium absorption from 1 and 10 mM of calcium gluconate solution. It is associated with the formation of the complex of Ca (II) ions with phosvitin. The process of calcium permeation increases under phosvitin influence when calcium gluconate concentrations rise up to 10 mM. At a higher concentration of calcium gluconate (20 mM), no effect of phosvitin was seen on permeation of calcium ions.

  13. Oral drug absorption in pediatrics: the intestinal wall, its developmental changes and current tools for predictions

    PubMed Central

    Bouzom, François; Hugues, Chanteux; Ungell, Anna‐Lena

    2017-01-01

    Abstract The dissolution, intestinal absorption and presystemic metabolism of a drug depend on its physicochemical characteristics but also on numerous physiological (e.g. gastrointestinal pH, volume, transit time, morphology) and biochemical factors (e.g. luminal enzymes and flora, intestinal wall enzymes and transporters). Over the past decade, evidence has accumulated indicating that these factors may differ in children and adults resulting in age‐related changes in drug exposure and drug response. Thus, drug dosage may require adjustment for the pediatric population to ensure the desired therapeutic outcome and to avoid side‐effects. Although tremendous progress has been made in understanding the effects of age on intestinal physiology and function, significant knowledge gaps remain. Studying and predicting pharmacokinetics in pediatric patients remains challenging due to ethical concerns associated with clinical trials in this vulnerable population, and because of the paucity of predictive in vitro and in vivo animal assays. This review details the current knowledge related to developmental changes determining intestinal drug absorption and pre‐systemic metabolism. Supporting experimental approaches as well as physiologically based pharmacokinetic modeling are also discussed together with their limitations and challenges. © 2016 UCB Biopharma sprl. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons, Ltd. PMID:27976409

  14. In Silico Prediction for Intestinal Absorption and Brain Penetration of Chemical Pesticides in Humans

    PubMed Central

    Chedik, Lisa; Mias-Lucquin, Dominique; Bruyere, Arnaud; Fardel, Olivier

    2017-01-01

    Intestinal absorption and brain permeation constitute key parameters of toxicokinetics for pesticides, conditioning their toxicity, including neurotoxicity. However, they remain poorly characterized in humans. The present study was therefore designed to evaluate human intestine and brain permeation for a large set of pesticides (n = 338) belonging to various chemical classes, using an in silico graphical BOILED-Egg/SwissADME online method based on lipophilicity and polarity that was initially developed for drugs. A high percentage of the pesticides (81.4%) was predicted to exhibit high intestinal absorption, with a high accuracy (96%), whereas a lower, but substantial, percentage (38.5%) displayed brain permeation. Among the pesticide classes, organochlorines (n = 30) constitute the class with the lowest percentage of intestine-permeant members (40%), whereas that of the organophosphorus compounds (n = 99) has the lowest percentage of brain-permeant chemicals (9%). The predictions of the permeations for the pesticides were additionally shown to be significantly associated with various molecular descriptors well-known to discriminate between permeant and non-permeant drugs. Overall, our in silico data suggest that human exposure to pesticides through the oral way is likely to result in an intake of these dietary contaminants for most of them and brain permeation for some of them, thus supporting the idea that they have toxic effects on human health, including neurotoxic effects. PMID:28665355

  15. Effects of quercetin and menadione on intestinal calcium absorption and the underlying mechanisms.

    PubMed

    Marchionatti, Ana M; Pacciaroni, Adriana; Tolosa de Talamoni, Nori G

    2013-01-01

    Quercetin (QT) could be considered as a potential therapeutic agent for different diseases due to its antioxidant, anti-inflammatory, antiviral and anticancer properties. This study was designed to investigate the ability of QT to protect the chick intestine against menadione (MEN) induced injury in vivo and in vitro. Four-week old chicks (Gallus gallus) were treated i.p. with 2.5μmol of MEN/kg b.w. or with i.l. 50μM QT or both. QT protected the intestinal Ca(2+) absorption against the inhibition caused by MEN, but QT alone did not modify. Glutathione (GSH) depletion provoked by MEN in chick enterocytes was abolished by QT treatment, whereas QT alone did not modify the intestinal GSH content. The enhancement of GSH peroxidase activity produced by MEN was blocked by QT treatment. In contrast, superoxide dismutase activity remained high after simultaneous treatment of enterocytes with MEN and QT. The flavonol also avoided changes in the mitochondrial membrane permeability (swelling) produced by MEN. The FasL/Fas/caspase-3 pathway was activated by MEN, effect that was abrogated by QT. In conclusion, QT may be useful in preventing inhibition of chick intestinal Ca(2+) absorption caused by MEN or other substances that deplete GSH, by blocking the oxidative stress and the FasL/Fas/caspase-3 pathway activation.

  16. [Effect of wujia bugu recipe on intestinal calcium absorption in rats under simulated weightlessness manner].

    PubMed

    Hu, Su-Min; Zhou, Peng; Fu, Qian

    2009-08-01

    To investigate the intervention effect of Wujia Bugu Recipe (WBR, consisting of Radix Rehmanniae Praeparata, Radix Achyranthis bidentate, Radix Astragali, Radix Angelicae sinensis, acetolytic substance of Concha Ostreae) on the intestinal absorption of exogenous calcium in rats under simulated Weightlessness manner. Twenty-one male Wistar rats were randomly divided into 3 groups, the blank group, the model group, and the tested group treated with WBR via gastric perfusion. Simulated weightlessness manner was formed by tail suspending after rats' entry into an one-week adaptation stage. And a definite dose of 41Ca tracer was given to each rat by gastric administration on the 11th day of the weightless stage. Their 72 h feces were collected for measuring ratio of 41Ca/40Ca by accelerator mass spectrometry (AMS), the total calcium in feces was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES), the 41Ca feces content (FC) and intestinal absorption amount (AA), and then the calcium intestinal absorption ratio (AR) were analyzed and calculated. 41Ca/40Ca ratio and 41Ca FC were higher, 41Ca AA and AR were lower in the model group than those in the blank group, the differences between groups were significant (P <0.01); while in the tested group, the differences of all above-mentioned indices with those in the blank group were insignificant, although the 41Ca/40Ca ratio showed somewhat increased, yet the increment was less than that in the model group (P <0.05). Simulated weightlessness could lead to decrease of intestinal calcium absorption, which could be improved to some extent by Chinese herbal medicine.

  17. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin.

    PubMed

    Huo, Xiaokui; Liu, Qi; Wang, Changyuan; Meng, Qiang; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi; Liu, Kexin

    2013-11-20

    Bestatin is an immunomodulator with antitumor activity. This study was performed to investigate the effect of P-gp on the intestinal absorption and antiproliferative activity of bestatin. Our results showed that P-gp inhibitors significantly increased rat intestinal absorption of bestatin in vivo and in vitro. The net efflux ratio of bestatin was 2.2 across mock-/MDR1-MDCK cell monolayers and was decreased by P-gp inhibitors, indicating bestatin was a substrate of P-gp. Furthermore, the IC50 values of bestatin on U937 and K562 cells were decreased dramatically and the intracellular concentrations of bestatin were increased by incubation of cells with verapamil or Cyclosporin A. K562/ADR cells exhibited a higher IC50 value and a lower intracellular level of bestatin. The bestatin level in K562/ADR cells was partially restored by incubation with doxorubicin. However, P-gp and APN mRNA levels were not changed by bestatin. These results suggested that the intestinal absorption and accumulation in cancer cells for bestatin were limited by P-gp-mediated efflux. Additional attention should be paid to the alternative exposure of bestatin when bestatin was coadministered with drugs as P-gp substrates in clinic.

  18. Effect of chito-oligosaccharide on the intestinal absorptions of phenylethanoid glycosides in Fructus Forsythiae extract.

    PubMed

    Zhou, Wei; Tan, Xiaobin; Shan, Jinjun; Liu, Ting; Cai, Baochang; Di, Liuqing

    2014-10-15

    Phenylethanoid glycosides, the main active ingredients in Fructus Forsythiae extract possesses strong antibacterial, antioxidant and antiviral effects, and their contents were higher largely than that of other ingredients such as lignans and flavones, but their absolute bioavailability orally was significantly low, which influenced clinical efficacies of its oral preparations seriously. In the present study, the absorption mechanism of phenylethanoid glycosides was studied using in vitro Caco-2 cell model. And the effect of chito-oligosaccharide (COS) on the intestinal absorption of phenylethanoid glycosides in Fructus Forsythiae extract was investigated using in vitro, in situ and in vivo models. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenylethanoid glycosides in Fructus Forsythiae extract so with that in monomers was mainly restricted by the tight junctions, and influenced by efflux transporters (P-gp and MRP2). Meanwhile, the absorption of phenylethanoid glycosides in Fructus Forsythiae extract could be improved by COS. Besides, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenylethanoid glycosides compared to the control group (p<0.05), and was all safe for the Caco-2 cells. The observations from single-pass intestinal perfusion in situ model showed that the intestinal absorption of phenylethanoid glycosides can be enhanced by COS. Meanwhile, the absorption enhancing effect of phenylethanoid glycosides might be saturable in different intestine sites. In pharmacokinetics study, COS at dosage of 25mg/kg improved the bioavailability of phenylethanoid glycosides in Fructus Forsythiae extract to the greatest extent, and was safe for gastrointestine from morphological observation. In addition

  19. 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

  20. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.

    PubMed

    Yan, Chengyun; Gu, Jiwei; Lv, Yuguang; Shi, Weiguo; Jing, Hongying

    2017-03-16

    In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1-1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1-0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.

  1. Prediction of drug intestinal absorption in human using the Ussing chamber system: A comparison of intestinal tissues from animals and humans.

    PubMed

    Miyake, Masateru; Koga, Toshihisa; Kondo, Satoshi; Yoda, Noriaki; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

    2017-01-01

    An adequate evaluation system for drug intestinal absorption is essential in the pharmaceutical industry. Previously, we established a novel prediction system of drug intestinal absorption in humans, using the mini-Ussing chamber equipped with human intestinal tissues. In this system, the TI value was defined as the sum of drug amounts transported to the basal-side component (X(corr)) and drug amounts accumulated in the tissue (T(corr)), which are normalized by AUC of a drug in the apical compartment, as an index for drug absorption. In order to apply this system to the screening assay, it is important to understand the differences between animal and human tissues in the intestinal absorption of drugs. In this study, the transport index (TI) values of three drugs, with different levels of membrane permeability, were determined to evaluate the rank order of drug absorbability in intestinal tissues from rats, dogs, and monkeys. The TI values in small intestinal tissues in rats and dogs showed a good correlation with those in humans. On the other hand, the correlation of TI values in monkeys was lower compared to rats and dogs. The rank order of the correlation coefficient between human and investigated animal tissues was as follows: dog (r(2)=0.978), rat (r(2)=0.955), and monkey (r(2)=0.620). TI values in large intestinal tissues from rats (r(2)=0.929) and dogs (r(2)=0.808) also showed a good correlation. The obtained TI values in small intestinal tissues in rats and dogs were well correlated with the fraction of drug absorbed (Fa) in humans. From these results, the mini-Ussing chamber, equipped with intestinal tissues in rats and dogs, would be useful as a screening tool in the drug discovery stage. In addition, the obtained TI values can be used for the prediction of the Fa in humans.

  2. Identification of Nramp2 as an iron transport protein: another piece of the intestinal iron absorption puzzle.

    PubMed

    Fleet, J C

    1998-03-01

    Although a number of iron-binding proteins have been identified, the roles for specific proteins in mediating iron absorption have not been definitively assigned. Two recent papers report the identification of an iron transport protein that may be responsible for movement of iron from the intestinal lumen into the enterocyte. Coupled with the recent identification of the protein mutated in hemochromatosis, researchers are now establishing a clearer picture of the mechanism of intestinal iron absorption.

  3. 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.

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

    PubMed

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

    2004-10-01

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

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

    PubMed

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

    2012-07-01

    The effect of chitosan on the intestinal absorption of acyclovir (ACV) was evaluated in rats, and factors influencing its facilitative effect on the ACV absorption were examined. When ACV solution containing 1% chitosan with an average molecular weight of 150 kDa was administered into the upper jejunum, a significant increase in the plasma ACV concentration was observed, with the peak ACV concentration being eight times greater than that observed with the chitosan-free solution. The chitosan-free ACV solution, whose viscosity was adjusted to remain unchanged with polyethylene glycol, did not cause an increase in the plasma concentration, and neither did the chitosan-free solutions substitutionally containing low molecular cationic compounds, triethanolamine and kanamycin. When chitosan was digested with chitosanase to shorten its polycationic polysaccharide structure, chitosan subjected to 150-min digestion retained its facilitative effect on ACV absorption, but that subjected to 420-min digestion no longer caused facilitation, in which its average molecular weight was reduced to around 10 kDa. It is therefore indicated that intestinal ACV absorption can be facilitated with chitosan, and that it is necessary for chitosan to have a certain length of polycationic polysaccharide structure to exert such facilitation. Copyright © 2012 Wiley Periodicals, Inc.

  6. Trpv6 mediates intestinal calcium absorption during calcium restriction and contributes to bone homeostasis

    PubMed Central

    Lieben, L.; Benn, B. S.; Ajibade, D.; Stockmans, I.; Moermans, K.; Hediger, M.A.; Peng, J.B.; Christakos, S.; Bouillon, R.; Carmeliet, G.

    2010-01-01

    Energy-dependent intestinal calcium absorption is important for the maintenance of calcium and bone homeostasis, especially when dietary calcium supply is restricted. The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a crucial regulator of this process and increases the expression of the transient receptor potential vanilloid 6 (Trpv6) calcium channel that mediates calcium transfer across the intestinal apical membrane. Genetic inactivation of Trpv6 in mice (Trpv6−/−) showed, however, that TRPV6 is redundant for intestinal calcium absorption when dietary calcium content is normal/high and passive diffusion likely contributes to maintain normal serum calcium levels. At the other hand, Trpv6 inactivation impaired the increase in intestinal calcium transport following calcium restriction, however without resulting in hypocalcemia. A possible explanation is that normocalcemia is maintained at the expense of bone homeostasis, a hypothesis investigated in this study. In this study, we thoroughly analyzed the bone phenotype of Trpv6−/− mice receiving a normal (~ 1%) or low (~ 0.02%) calcium diet from weaning onwards using micro-computed tomography, histomorphometry and serum parameters. When dietary supply of calcium is normal, Trpv6 inactivation did not affect growth plate morphology, bone mass and remodeling parameters in young adult or ageing mice. Restricting dietary calcium had no effect on serum calcium levels and resulted in a comparable reduction in bone mass accrual in Trpv6+/+ and Trpv6−/− mice (−35% and 45% respectively). This decrease in bone mass was associated with a similar increase in bone resorption, whereas serum osteocalcin levels and the amount of unmineralized bone matrix were only significantly increased in Trpv6−/− mice. Taken together, our findings indicate that TRPV6 contributes to intestinal calcium transport when dietary calcium supply is limited and in this condition indirectly regulates bone formation

  7. 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.

  8. 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.

  9. 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

  10. Assessment and modulation of forsythiaside absorption with MDCKII cells and validation with in situ intestinal experiment.

    PubMed

    Li, Yun-Xia; Zhang, Ruo-Qi; Peng, Cheng

    2012-09-01

    Forsythiaside was characterized by low intestinal absorption by in situ rat experiment and Caco-2 cells. The mechanisms behind this low absorption had not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of forsythiaside as a potential mechanism for its low small-intestinal absorption following oral administration. Polarized MDCKII cell lines stably transfected with human or murine complementary DNA encoding for various efflux transporters (P-gp/MDR1, MRP2 and Bcrp1) were used to study transepithelial transport of forsythiaside and compare results with the MDCKII-Wild type cells. The transportation inhibitors GF120918, MK571 and Ko143 were used to investigate the transport mechanism. The active transport of forsythiaside was found in MDCKII-WT cells. The MDCKII-MRP2 and MDCKII-Bcrp1 cells significantly increased forsythiaside efflux ratio compared with the parental cells due to the apically directed transport by MRP2 and Bcrp1, respectively. The efflux ratios in MRP2 and Bcrp1 transfected cell lines were greatly decreased in the presence of MK-571 and Ko143, respectively, which indicated that forsythiaside efflux by MRP2 and Bcrp1 were significantly inhibited by their selective inhibitors. MDCKII-MDR1 cells did not exhibit a significant reduction in the forsythiaside efflux compared with the parental cells, indicating that it was not a good substrate for MDR1. And the results were then validated by the in situ experiment. This study presents direct evidence that forsythiaside is effluxed by both MRP2 and Bcrp1, which may contribute to its poor oral bioavailability.

  11. Prediction of Human intestinal absorption of compounds using artificial intelligence techniques.

    PubMed

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-04-04

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. In current work, we are presenting a comprehensive study of prediction of absorption. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds with prediction accuracy of 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. The effect of auranofin on glucose uptake by the isolated vascularly perfused, small intestine of the rat.

    PubMed

    McMaster, D; Love, A H

    1987-11-01

    Auranofin at a concentration of 2.5 micrograms/ml had no effect on glucose uptake by the viable, isolated, vascularly perfused, small intestine of the rat and no net movement of water was detected. No effect on glucose uptake or water movement was found when intestines from rats fed 0.1 mg/Kg body weight per day for 4 weeks were perfused with drug free medium. Mucosal damage was seen in 1 of 2 rats fed Auranofin and examined histologically.

  13. Mouse Atonal Homolog 1 Directs Intestinal Progenitors to Secretory Cell Rather than Absorptive Cell Fate

    PubMed Central

    VanDussen, Kelli L.; Samuelson, Linda C.

    2010-01-01

    The Notch-regulated transcription factor mouse atonal homolog 1 (Math1) is required for the development of intestinal secretory cells, as demonstrated by the loss of goblet, endocrine and Paneth cell types in null mice. However, it was unknown whether Math1 is sufficient to induce the program of secretory cell differentiation. To examine the function of Math1 in the differentiation of intestinal epithelial cells, intestinal morphology and epithelial and mesenchymal cell fate were examined by histological staining and marker gene expression in transgenic mice expressing a villin-regulated Math1 transgene. Late prenatal transgenic founders exhibited a gross cellular transformation into a secretory epithelium. The expansion of secretory cells coupled with the almost complete loss of absorptive enterocytes suggested reprogramming of a bipotential progenitor cell. Moreover, Math1 expression inhibited epithelial cell proliferation, as demonstrated by a marked reduction in Ki67 positive cells and blunted villi. Unexpectedly, the transgenic mesenchyme was greatly expanded with increased proliferation. Several mesenchymal cell types were amplified, including smooth muscle and neurons, with maintenance of basic radial patterning. Since transgenic Math1 expression was restricted to the epithelium, these findings suggest that epithelial-mesenchymal signaling is altered by the cellular changes induced by Math1. Thus, Math1 is a key effector directing multipotential precursors to adopt secretory and not absorptive cell fate. PMID:20691176

  14. 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.

  15. Exploration of intestinal calcium precipitation as a barrier to absorption at high calcium doses.

    PubMed

    Goss, Sandra; Rafferty, Pauline; Prushko, Jennifer; Gorman, Eric; Taub, Mitchell; Bogner, Robin

    2008-12-01

    To investigate the hypothesis that intestinal bicarbonate secretions precipitate calcium as the carbonate salt, thereby resulting in poor absorption (20-40%) from calcium supplements. The in vitro effect of calcium dose and bicarbonate secretion rate on soluble calcium was determined by neutralizing elemental Ca(2+)(250, 475, and 630 mg) in 0.1 N HCl to pH 7 with a bicarbonate secretion rate of 0.12 or 1.2 mEq/min. P (CO2) and pH of the solutions were monitored. Soluble calcium was analyzed using atomic absorption spectrometry. Additionally, the transport of calcium across Caco-2 cell monolayers was determined. Calcium from a 250 mg dose remained soluble during bicarbonate secretion, regardless of rate. Once the dose increased, the calcium remaining in solution decreased during neutralization with bicarbonate. The Ca(2+)/CaHCO(3) (+) ratio had no effect on calcium permeation across Caco-2 cell monolayers. The physicochemical mechanism of intestinal calcium precipitation supports published clinical data by suggesting that once the solubility product of calcium carbonate is reached, increasing the calcium dose results in significant precipitation at intestinal pH values.

  16. Protective effect of glucose-insulin-potassium (GIK) on intestinal tissues after severe burn in experimental rats.

    PubMed

    Wang, Zhanke; Liu, Longyan; Hu, Tian; Lei, Wansheng; Wan, Fusheng; Zhang, Ping; Wang, Zhen; Xu, Jinsong; Zhu, Haohao; Zhu, Zhongzhen; Yang, Yang; Hu, Xiaolu; Xu, Linshui; Wang, Shiliang

    2012-09-01

    Intestinal barrier damage after scald and burns, other trauma or major operations result in severe intestinal infections that cause serious consequences. Therefore, it is important to develop methods to protect intestinal barrier after severe burns. This study used rats that had full-thickness burn of approximately 30% of the total body surface area to investigate the effect and mechanism of glucose-insulin-potassium (GIK) and provide experimental evidence for application of GIK in protecting the intestine after burns or other trauma and major surgeries. The results show that the degree of intestinal damage and plasma diamine oxidase (DAO) levels in GIK (the concentrations of glucose, insulin, sodium chloride and potassium chloride were 100 g l(-1), 70 U l(-1), 9 g l(-1) and 5 g l(-1), respectively) and insulin (30 IU l(-1)) treatment groups were significantly lower than that in control group; the status of anti-inflammatory and pro-inflammatory cytokines and the ratio between them in GIK and insulin groups also significantly improved compared to those in control group; intestinal tumour necrosis factor-alpha (TNFα), nuclear factor-kappaB (NF-κB) and interleukin-10 (IL-10) messenger RNA (mRNA) expression and IL10/TNFα in GIK and insulin groups 2 days after the injury were also improved significantly compared to those in control group. All the indices including body weight detected in GIK group were improved to those in insulin group. Taken together, these results show that GIK and insulin show protective effect on intestine after severe burn, which may relate to controlling hyperglycaemia and regulating intestinal expression of NFκB and pro-inflammatory and anti-inflammatory cytokine genes by GIK and insulin; the protective effect of GIK on intestinal tissue after severe burn is superior to that of using insulin alone, which may attribute to improving the nutritional status by glucose supplement and the relatively higher dose of insulin in the GIK group.

  17. A preliminary study on the absorption of isometamidium chloride (Samorin) in the stomach and small intestine of rat.

    PubMed

    Ogun, C O; Eghianruwa, K I

    1993-04-01

    The levels of absorption of isometamidium chloride (Samorin) in the stomach and intestine of the rat were determined because of problems usually associated with parenteral administration of the drug. The in situ loop method and in situ recirculation technique were used to determine the absorption of the drug in the stomach and intestine respectively. 54.8% of isometamidium chloride was absorbed in the stomach in 30 minutes while 2% was absorbed in the intestine in one hour. These results warrant the comparative study of the blood and tissue concentrations of isometamidium chloride following oral and parenteral administration.

  18. 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.

  19. 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

  20. Vesicular transport and apotransferrin in intestinal iron absorption, as shown in the Caco-2 cell model.

    PubMed

    Moriya, Mizue; Linder, Maria C

    2006-02-01

    The potential roles of vesicular transport and apotransferrin (entering from the blood) in intestinal Fe absorption were investigated using Caco-2 cell monolayers with tight junctions in bicameral chambers as a model. As shown previously, addition of 39 microM apotransferrin (apoTf) to the basolateral fluid during absorption studies markedly stimulated overall transport of 1 microM (59)Fe from the apical to the basal chamber and stimulated its basolateral release from prelabeled cells, implicating endo- and exocytosis. Rates of transport more than doubled. Uptake was also stimulated, but only 20%. Specific inhibitors of aspects of vesicular trafficking were applied to determine their potential effects on uptake, retention, and basolateral (overall) transport of (59)Fe. Nocodazole and 5'-(4-fluorosulfonylbenzoyl)-adenosine each reduced uptake and basolateral transport up to 50%. Brefeldin A inhibited about 10%. Tyrphostin A8 (AG10) reduced uptake 35% but markedly stimulated basolateral efflux, particularly that dependent on apoTf. Cooling of cells to 4 degrees C (which causes depolymerization of microtubules and lowers energy availability) profoundly inhibited uptake and basolateral transfer of Fe (7- to 12-fold). Apical efflux (which was substantial) was not temperature affected. Our results support the involvement of apoTf cycling in intestinal Fe absorption and indicate that as much as half of the iron uses apoTf and non-apoTf-dependent vesicular pathways to cross the basolateral membrane and brush border of enterocytes.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Two weeks of moderate intensity continuous training, but not high intensity interval training increases insulin-stimulated intestinal glucose uptake.

    PubMed

    Motiani, Kumail Kumar; Savolainen, Anna M; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A; Parkkola, Riitta; Kapanen, Jukka; Gronroos, Tove J; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-02-09

    Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy middle-aged sedentary men were randomized for two weeks of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [(18)F]FDG and [(18)F]FTHA. In addition, effects of HIIT and MICT on intestinal Glut2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (p=0.001) and whole-body insulin sensitivity (p=0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon [HIIT=0%; MICT=37%] (p=0.02 for time*training) and tended to increase in the jejunum [HIIT=-4%; MICT=13%] (p=0.08 for time*training). Fasting free fatty acid uptake decreased in the duodenum in both groups [HIIT=-6%; MICT=-48%] (p=0.001 time) and tended to decrease in the colon in the MICT group [HIIT=0%; MICT=-38%] (p=0.08 for time*training). In rats, both training groups had higher Glut2 and CD36 expression compared to control animals. This study shows that already two weeks of MICT enhances insulin-stimulated glucose uptake while both training modes reduce fasting free fatty acid uptake in the intestine in healthy middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.

  3. The use of low molecular weight protamine chemical chimera to enhance monomeric insulin intestinal absorption.

    PubMed

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

    2013-10-01

    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 non-toxic 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 homogenous, 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.

  4. 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

  5. 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.

  6. 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

  7. Bomb calorimetry, the gold standard for assessment of intestinal absorption capacity: normative values in healthy ambulant adults.

    PubMed

    Wierdsma, N J; Peters, J H C; van Bokhorst-de van der Schueren, M A E; Mulder, C J J; Metgod, I; van Bodegraven, A A

    2014-04-01

    Intestinal absorption capacity is considered to be the best method for assessing overall digestive intestinal function. Earlier reference values for intestinal function in healthy Dutch adults were based on a study that was conducted in an inpatient metabolic unit setting in a relatively small series. The present study aimed to readdress and describe the intestinal absorption capacity of healthy adults, who were consuming their usual (Western European) food and beverage diet, in a standard ambulatory setting. Twenty-three healthy subjects (aged 22-60 years) were included in the analyses. Nutritional intake (energy and macronutrients) was determined with a 4-day nutritional diary. Subsequently, mean faecal losses of energy (by bomb calorimetry), fat, protein and carbohydrate were determined following a 3-day faecal collection. Finally, intestinal absorption capacity was calculated from the differences between intake and losses. Mean (SD) daily faeces production was 141 (49) g (29% dry weight), containing 891 (276) kJ [10.7 (1.3) kJ g(-1) wet faeces; 22.6 (2.5) kJ g(-1) dry faeces], 5.2 (2.2) g fat, 10.0 (3.8) g protein and 29.7 (11.7) g carbohydrates. Mean (SD) intestinal absorption capacity of healthy subjects was 89.4% (3.8%) for energy, 92.5% (3.7%) for fat, 86.9% (6.4%) for protein and 87.3% (6.6%) for carbohydrates. The present study provides normative values for both stool nutrient composition and intestinal energy and macronutrient absorption in healthy adults on a regular Dutch diet in an ambulatory setting. Intestinal energy absorption was found to be approximately 90%. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

  8. Effect of the artificial sweetener, acesulfame potassium, a sweet taste receptor agonist, on glucose uptake in small intestinal cell lines.

    PubMed

    Zheng, Ye; Sarr, Michael G

    2013-01-01

    Sweet taste receptors may enhance glucose absorption. This study aimed to explore the cell biology of sweet taste receptors on glucose uptake. 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. 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. 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 (PLC βII inhibitor) 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. 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). Role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself.

  9. Enhancing effects of chitosan and chitosan hydrochloride on intestinal absorption of berberine in rats.

    PubMed

    Chen, Wei; Fan, Dongjiao; Meng, Lingkuo; Miao, Yuqiang; Yang, Shenshen; Weng, Yan; He, Haibing; Tang, Xing

    2012-01-01

    Berberine chloride (BBR) is a plant alkaloid that has been used for centuries for treatment of inflammation, dysentery, and liver diseases. It is poorly absorbed from the gastrointestinal (GI) tract and its various clinical uses are limited because of its poor bioavailability. The object of the present study was to investigate the absorption enhancing effect of chitosan on BBR. Mixtures of BBR and chitosan were prepared and the absorption enhancement was investigated in rats. The results showed a dose-dependent absorption enhancement produced by chitosan. Formulations containing 0.5%, 1.5%, and 3.0% chitosan resulted in improvement of AUC(0-36 h) values by 1.9, 2.2, 2.5 times. The absorption enhancing ability of chitosan may be due to its ability to improve the BBR paracellular pathway in the intestinal tract. Chitosan hydrochloride, a salt of chitosan, was also investigated in this study. However, the addition of 2.0% and 3.3% chitosan hydrochloride to BBR solution did not produce any increase in either C(max) or AUC(0-36 h) of BBR. Subsequent solubility studies suggested that the reduced berberine chloride solubility in chitosan hydrochloride may limit the enhancement ability. This study showed that the optimum formulation producing the highest BBR absorption is the BBR solution containing 3.0% chitosan.

  10. Influence of gallate and pyrogallol moieties on the intestinal absorption of (-)-epicatechin and (-)-epicatechin gallate.

    PubMed

    Tagashira, Tomohiko; Choshi, Tominari; Hibino, Satoshi; Kamishikiryou, Jun; Sugihara, Narumi

    2012-10-01

    The cellular accumulation of individual catechins was measured as an index of intestinal absorption to clarify the interactions among catechins. The cellular accumulation of (-)-epicatechin (EC) increased in the presence of other catechins. The ability of gallate catechin such as (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) to increase the cellular accumulation of EC was greater than that of nongallate catechins. Gallic acid octyl ester (GAO) also increased the cellular accumulation of EC by 426% as compared with that in untreated cells. Conversely, the cellular accumulation of ECG was not influenced by other catechins, but it increased by 54% in the presence of GAO. Experiments using GAO derivatives indicated that the gallate moiety required the presence of a catechol group and a neighboring carbonyl group, whereas the pyrogallol moiety, without a neighboring carbonyl group, required 3 hydroxyl groups to increase the cellular accumulation of EC. Furthermore, gallate esters required long carbon chains to increase the same. The experiment using EGCG, GAO, or their derivatives indicated that the ability of gallate or pyrogallol moiety to increase the cellular accumulation of EC was restricted by their hydrophobicity. These results suggest that the co-administration of foods containing functional materials such as gallate or pyrogallol moieties, increases the intestinal absorption of catechin. The cellular accumulation of (-)-epicatechin increased by the gallate or pyrogallol moiety in catechin structure. The interaction among catechins appeared to affect intestinal absorption of catechin. The bioavailability of catechin may be improved by co-administration of functional foods. © 2012 Institute of Food Technologists®

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

    PubMed Central

    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.

    2014-01-01

    The ferritin core is composed of fine nanoparticulate Fe3+ oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe3+ polyoxohydroxide (nanoFe3+). 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 Fe2+ sulfate (FeSO4), nanoFe3+, or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe3+ was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe3+ 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 nanoFe3+ group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe3+ 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.—Aslam, M. F., Frazer, D. M., Faria, N., Bruggraber, S. F. A., Wilkins, S. J., Mirciov, C., Powell, J. J., Anderson, G. J., Pereira, D. I. A. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice. PMID:24776745

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

    PubMed

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

    2012-04-01

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

  13. Intestinal absorption of carnosine and its constituent amino acids in man 1

    PubMed Central

    Asatoor, A. M.; Bandoh, J. K.; Lant, A. F.; Milne, M. D.; Navab, F.

    1970-01-01

    Serum concentrations of β-alanine and l-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (β-alanyl-l-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion of the amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves. PMID:5423906

  14. Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats.

    PubMed

    Chuang, Er-Yuan; Lin, Kun-Ju; Su, Fang-Yi; Mi, Fwu-Long; Maiti, Barnali; Chen, Chiung-Tong; Wey, Shiaw-Pyng; Yen, Tzu-Chen; Juang, Jyuhn-Huarng; Sung, Hsing-Wen

    2013-12-10

    This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with ethylene glycol tetraacetic acid (γPGA-EGTA) for oral insulin delivery in diabetic rats during an oral glucose tolerance test (OGTT). OGTT has been used largely as a model to mimic the period that comprises and follows a meal, which is often associated with postprandial hyperglycemia. Based on Förster resonance energy transfer (FRET), this work also demonstrated the ability of γPGA-EGTA to protect insulin from an intestinal proteolytic attack in living rats, owing to its ability to deprive the environmental calcium. Additionally, EGTA-conjugated NPs were effective in disrupting the epithelial tight junctions, consequently facilitating the paracellular permeation of insulin throughout the entire small intestine. Moreover, results of positron emission tomography and computer tomography demonstrated the effective absorption of the permeated insulin into the systemic circulation as well as promotion of the glucose utilization in the myocardium, and skeletal muscles of the chest wall, forelimbs and hindlimbs, resulting in a significant glucose-lowering effect. Above results indicate that as-prepared EGTA-conjugated NPs are a promising oral insulin delivery system to control postprandial hyperglycemia and thus may potentially prevent the related diabetic complications. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Molecular and cellular studies on the absorption, function, and safety of food components in intestinal epithelial cells.

    PubMed

    Satsu, Hideo

    2017-03-01

    The intestinal tract comes into direct contact with the external environment despite being inside the body. Intestinal epithelial cells, which line the inner face of the intestinal tract, have various important functions, including absorption of food substances, immune functions such as cytokine secretion, and barrier function against xenobiotics by means of detoxification enzymes. It is likely that the functions of intestinal epithelial cells are regulated or modulated by these components because they are frequently exposed to food components at high concentrations. This review summarizes our research on the interaction between intestinal epithelial cells and food components at cellular and molecular levels. The influence of xenobiotic contamination in foods on the cellular function of intestinal epithelial cells is also described in this review.

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

    PubMed

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

    2015-11-01

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

  17. Effect of vitamin D on the intestinal absorption of /sup 203/Pb and /sup 47/Ca in chicks

    SciTech Connect

    Mykkaenen, H.M.; Wasserman, R.H.

    1982-03-01

    The transfer of /sup 203/Pb and/or /sup 47/Ca across the intestinal epithelium of the chick was investigated, with emphasis given to the functional role of cholecalciferol (vitamin D-3). /sup 203/Pb, after introduction in the intestinal lumen, is rapidly accumulated by the intestinal tissue, and only a fraction of /sup 203/ Pb is translocated parenterally (absorbed). Cholecalciferol did not significantly affect the accumulation of /sup 203/Pb by intestinal tissue but did accelerate /sup 203/Pb movement across the basal-lateral membrane. In contrast, cholecalciferol both decreased /sup 47/Ca tissue levels and increased /sup 47/Ca absorption. In rachitic chicks, the rate of absorption of /sup 203/Pb was greater in the distal than in the proximal segments of the intestine; after cholecalciferol repletion, the degree of absorption in all segments was similar, indicating the order of cholecalciferol effectiveness as duodenum greater than or equal to jejunum > ileum. An acute dose of 1,25(OH)/sub 2/D/sub 3/ to rachitic chicks also enhanced both /sup 203/Pb and /sup 47/Ca absorption, but the time course and pattern of absorption of these metal cations differed. The time at which the absorption of /sup 203/Pb peaked and returned to base-line occurred sooner than for /sup 47/Ca. Also the back-flux (blood ..-->.. intestinal lumen) of /sup 47/Ca was enhanced by cholecalciferol, whereas no effect on the back-flux of /sup 203/Pb was noted. These studies show that cholecalciferol and 1,25(OH)/sub 2/D/sub 3/ affects both the /sup 203/Pb and /sup 47/Ca absorptive processes, but the nature of these responses are not identical, suggesting differences in the transport path or the macromolecular interactions of these metal ions during the course of absorption, or both.

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

    PubMed

    Hyde, Michelle L; Fraser, David R

    2014-09-14

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

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

    PubMed

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

    2015-08-01

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