HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hartke, J. L. Articles by Donovan, S. M. Search for Related Content PubMed PubMed Citation Articles by Hartke, J. L. Articles by Donovan, S. M.

Effect of a short-term fast on intestinal disaccharidase activity and villus morphology of piglets suckling insulin-like growth factor-I transgenic sows¹

J. L. Hartke^*, M. H. Monaco^*, M. B. Wheeler and S. M. Donovan^*,2

^* Division of Nutritional Sciences and and Department of Animal Sciences and the Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana 61801

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 
The objectives of this study were to use transgenic sows that overexpress IGF-I in milk to investigate the effect of a short-term fast on piglet intestinal morphology and disaccharidase activity and to determine how milk-borne IGF-I influences the response to fasting. After farrowing, litters were normalized to 10 piglets. On d 6, piglets (n = 30) suckling IGF-I transgenic (TG) sows and piglets (n = 30) suckling nontransgenic sows (control) were assigned randomly to three treatments: fed piglets (0 h), which remained with the sow until euthanized on d 7, or fasted piglets, which were removed from the sow at either 6 or 12 h before euthanasia on d 7. Serum IGF-I and IGFBP, intestinal weight and length, jejunal protein and DNA content, disaccharidase activity, and villus morphology were measured. Fasting for 12 h resulted in a negative weight change between d 6 and 7 (quadratic response to fasting; P < 0.001). Piglets suckling TG sows tended to have greater intestinal length (P = 0.068), but no effect of IGF-I overexpression was noted for intestinal weight. Fasting, however, resulted in linear (P < 0.001) and quadratic (P = 0.002) decreases in intestinal weight. Serum IGF-I did not differ between control and TG sows, but decreased linearly (P = 0.003) with fasting. Serum IGFBP-4 decreased (linear and quadratic; P 0.02) with fasting, whereas IGFBP-1 increased quadratically (P < 0.001) with fasting. Jejunal villus height, width, and crypt depth were all increased with fasting (linear and quadratic; P < 0.04). Disaccharidase activity was not affected by fed state; however, piglets suckling TG sows had greater jejunal lactase-phlorhizin hydrolase (P < 0.01) and sucrase-isomaltase (P = 0.02) activities than control piglets. In summary, intestinal weight, villus morphology, serum IGF-I, serum IGFBP-1 and -4, and piglet BW change were altered (P 0.02) in response to fasting. Thus, the duration of food deprivation before euthanization should be considered when designing experiments to assess intestinal development or the IGF axis, as the magnitude of differences between the fed and fasted state may exceed those expected as a result of experimental treatment.

Key Words: Enzyme • Fasting • Insulin-Like Growth Factor-I • Intestine • Piglet • Transgenic

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 
The gastrointestinal tract is the first organ system directly affected by changes in nutrient intake, and it displays both acute and long-term adaptation to food restriction (Ferraris and Carey, 2000). As feeding acutely regulates intestinal nutrient transporters (Cui et al., 2003; Pan et al., 2004) and disaccharidase activity (Goda, 2000), it is common to fast piglets before sample collection to decrease the variability in transporter and enzyme activities associated with feeding (Houle et al., 1997; Alexander and Carey, 2001). Intestinal responses to fasting for 24 h have been well described in adult rodents (Martins et al., 2001; Habold et al., 2004). Most pig studies have focused on ion and nutrient transport in weaning-aged animals after a minimum 24-h fast (Carey et al., 1994; Hayden and Carey, 2000). An analysis of the effect of short-term fasting in young piglets had not been conducted.

In previous studies, piglets fed formula containing recombinant human IGF-I exhibited greater intestinal villus height (Burrin et al., 1996) and lactase-phlorizin hydrolase (LPH) activity (Houle et al., 1997, 2000) than piglets fed formula alone. The increased LPH activity was associated with increased LPH mRNA abundance (Houle et al., 2000) and greater efficiency of post-translational processing of the proLPH to the mature LPH (Burrin et al., 2001). In these previous studies, the magnitude of the response of LPH activity to IGF-I treatment was greater in samples collected from piglets in a postabsorptive state (Park et al., 1999; Houle et al., 2000) than in a fed state (Burrin et al., 2001; Park et al., 2001). Therefore, the effect of duration of fasting on LPH activity in piglets suckling nontransgenic (control) and IGF-I transgenic (TG) sows was studied. We hypothesized that LPH activity would be greater in piglets suckling TG sows than control sows after a short-term fast. Intestinal morphology and circulating IGF-I and IGFBP also were assessed.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 
Animals and Experimental Design
Transgenic swine that exhibit mammary and lactation-specific overexpression of human IGF-I in milk under the direction of the 5'-regulatory elements of the bovine -lactalbumin gene (Donovan et al., 2001) and control full sib littermates were used. Eight control Yorkshire gilts and eight TG Yorkshire gilts were bred by natural service or artificial insemination to a Yorkshire boar. At d 109 of pregnancy, gilts were moved into farrowing crates and monitored for signs of parturition. At parturition, three control females and three TG females were selected randomly for use in this project. Within 6 h of farrowing, all litters were normalized to 10 piglets per gilt. If a litter contained <10 piglets, Yorkshire piglets from another gilt from the same treatment (control or TG) that farrowed on the same day were cross-fostered to standardize litter size. Whenever possible, the BW of cross-fostered piglets were approximately the mean birth weight of the piglets in the litter that they were joining. All piglets nursed until 1200 on d 6 postpartum, at which time all piglets were weighed, and piglets within each litter were assigned randomly to one of three treatment groups: fasted piglets were removed from the sow at either 6 or 12 h before (0300 on d 7 or 2100 on d 6, respectively) euthanasia at 0900 on d 7, whereas the 0-h piglets remained with the sow until euthanized at 0900 on d 7. All animal protocols and procedures were approved by the Biological Safety Committee and the Laboratory Animal Care Advisory Committee of the University of Illinois and were in compliance with NRC (1996) guidelines for the care and use of laboratory animals.

Sample Collection
Piglets were euthanized via sedation with sodium pentobarbital (0.1 mg/kg of BW; Fatal Plus, Vortech Pharmaceuticals, Dearborn, MI) followed by electrocution and exsanguination. Blood samples were collected, and serum was obtained by centrifugation at 3,500 x g for 15 min at 4°C. The entire small intestine from the pyloric sphincter to the ileocecal valve was immediately removed, and its length was measured. The intestine was divided into segments based on length: duodenum (first 10%), jejunum (middle 75%), and ileum (final 15%). Each segment was flushed with ice-cold saline, and its weight and length were recorded. Duodenal weights were inadvertently not recorded for one replicate; therefore, total intestinal weight could not be calculated, and the number of observations for that outcome is <30 for genotype and 20 for fasting. Beginning at the most proximal region of the jejunum, a jejunal section (2 cm) was fixed in formalin and embedded in paraffin. An additional section of jejunum (3 to 4 cm) was snap frozen in liquid N₂. The entire remaining portion of jejunum was opened longitudinally, and the mucosa was scraped from the luminal surface using a glass microscope slide.

Serum IGF.
Serum IGF-I content was measured by RIA as previously described (Houle et al., 1997). Serum samples (0.5 mL) were chromatographed in 0.2 M formic acid on a column containing Sephadex G-50 (Pharmacia Biotech Inc., Piscataway, NJ) to dissociate the IGF-I from the IGFBP. The IGF-I fraction was collected, frozen, and lyophilized (Labconco, Kansas City, MO). After lyophilization, samples were resolubilized in RIA buffer (0.03 M sodium phosphate and 0.25% sodium azide; pH 7.5) and diluted to 1:30. The IGF-I was measured using [¹²⁵I]IGF-I as the radioligand and a polyclonal anti-human IGF-I antibody, which was distributed through the National Hormone and Pituitary Program (http://www.humc.edu/hormones/). After overnight incubation, bound radioactivity was precipitated by centrifugation at 3,000 x g for 30 min after the addition of 1.0% bovine IgG (Sigma Chemical Co., St. Louis, MO) and 20% polyethylene glycol (Sigma Chemical Co.).

Serum IGFBP.
Serum IGFBP profiles were characterized by SDS-PAGE and Western ligand blotting as described previously (Houle et al., 1997). Four samples from each treatment group were selected randomly for use in analyses (n = 24). Sera were separated through 4% stacking and 12% running SDS-polyacrylamide gels at 65V, overnight at 4°C (Hoefer Scientific Instruments, San Francisco, CA). Size-separated proteins were electrotransferred to nitrocellulose (0.45 µm; Micron Separations Inc., Westborough, MA) at 200 mA for 1 h. Membranes were blocked through a series of washes (Houle et al., 1997) and then incubated overnight with 0.45 µCi of [¹²⁵I]IGF-I. Binding proteins were visualized by autoradiography (Eastman Kodak, Rochester, NY) at –70°C for 4 d. Images were captured using a Kodak Imaging Station 440, and band density was analyzed using Kodak 1D analysis software.

Mucosal Protein and DNA Content.
Mucosal protein and DNA content were measured using established methods (Houle et al., 2000). Mucosal samples (0.1 g) were homogenized in 1 mL of buffer containing protease inhibitors (0.45 M NaCl, 0.001 M phenylmethylsulfonyl fluoride, and 0.002 M iodoacetic acid). Protein content was measured by the Lowry method (Peterson, 1977) using BSA (Sigma Chemical Co.) to establish the standard curve. Homogenates were further diluted (1:10) in homogenization buffer before the protein assay. For the DNA assay, mucosal homogenates were diluted (1:20) in DNA buffer (2 mM EDTA, 2.0 M NaCl, and 50 mM NaPO4) and sonicated for 30 s (Fisher Scientific, Pittsburgh, PA). The DNA content was determined fluorometrically (excitation wavelength = 365 and emission wavelength = 460; VersaFluor, BioRad, Hercules, CA) using Hoescht H 33258 dye after dilution in DNA buffer and sonication for 30 s (Fisher Scientific). Calf thymus DNA (Sigma Chemical Co.) was used to generate the DNA standard curve.

Intestinal Histomorphology.
Ten samples from each treatment group were selected randomly for use in analyses (n = 30). Paraffin-embedded jejunal samples were sliced to approximately 5 µm with a microtome, mounted on slides, and stained with hematoxylin. Villus height from the tip of the villi to the villus/crypt junction, mid-villus width, and crypt depth were measured at 10x magnification using a Nikon microscope and Optiphot-2 software (Nikon, Melville, NY) in 10 to 20 well-oriented villi and crypts. Villus cross-sectional area was calculated by multiplying villus height and mid-villus width (Houle et al., 2000).

Disaccharidase Activity.
Mucosal disaccharidase activity was measured as described by Dudley et al. (1994). Mucosal samples were homogenized in homogenization buffer containing protease inhibitors. Sucrase-isomaltase (SI) and LPH activities were determined by incubating homogenates with the appropriate disaccharide (sucrose or lactose; Fisher Scientific) for 30 min at 37°C. The quantity of glucose liberated by mucosal disaccharidases was measured as an index of disaccharidase activity by coupling the reaction to glucose oxidase and peroxidase (Sigma Chemical Co.). Enzyme activities were expressed as µmol of glucose/(min·g of mucosal protein).

Statistical Analyses.
Data were analyzed as a completely randomized design using the GLM procedure of SAS (SAS Inst., Cary, NC). Within litters from control and TG sows, there were 30 piglets, 10 assigned to each fasting treatment (0-, 6-, or 12-h fast). Therefore, data were analyzed as a 2 (sow type) x 3 (fasting time) factorial arrangement of treatments. Separation of means for the effects of fasting time was accomplished using linear and quadratic contrasts. The interaction between sow type and fasting time was not significant for any variable; therefore, only the response to sow type and the linear and quadratic responses to fasting are presented. Comparisons with P < 0.05 were considered significant, and comparisons with P < 0.10 are presented as trends.

	Results

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 
Body Weight and Intestinal Weight and Length.
At sacrifice, BW was similar in all groups. The BW change in response to fasting was calculated by subtracting BW obtained at the same time from all groups on d 6 at 1200 from the BW at sacrifice on d 7 at 0900. Thus, of the 21-h period, 6-h fasted piglets had remained with the sow for 15 h, whereas the 12-h fasted piglets had remained with the sow for 9 h (Table 1). Weight change decreased quadratically (P < 0.001) with increasing fasting time. Piglets fasted for either 0 or 6 h had a positive weight gain between the d 6 weighing and sacrifice at d 7, whereas piglets fasted for 12 h lost 69.5 ± 48.39 g, or approximately 2.3% of their d-6 BW. All 0-h piglets had milk in their stomach and/ or jejunum at sacrifice, whereas none of the 6- or 12-h fasted piglets had digesta in their stomach or jejunum. Piglets suckling TG sows tended to have greater intestinal length (P = 0.068); however, no effect of fasting was observed on intestinal length. Conversely, intestinal weight was unaffected by IGF-I overexpression, but decreased in a linear (P < 0.001) and quadratic (P = 0.002) fashion with increasing fasting time (Table 1).

View larger version (87K): [in this window] [in a new window]   Figure 1. Jejunal histomorphology of 7-d-old piglets suckling control (CON) sows or transgenic (TG) sows that overexpress IGF-I in milk and fasted for 0, 6, or 12 h before sample collection. Images were captured at 10x magnification, and the bars shown in the 0-h panels are 100 µm in length.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

Body weights of piglets suckling control and TG sows were similar on d 6, which is consistent with earlier data documenting similar growth of piglets fed formula supplemented with or without recombinant IGF-I (Burrin et al., 1996; Houle et al., 1997, 2000). Circulating IGF-I concentrations in piglets suckling control or TG sows did not differ significantly, which is also consistent with previous findings in piglets fed formula alone or supplemented with IGF-I (Burrin et al., 1996; Houle et al., 1997, 2000). Furthermore, using [¹²⁵I]IGF-I as a tracer, we have shown that orally administered IGF-I is poorly absorbed in the neonatal piglet (Donovan et al., 1997). The length of time piglets were fasted influenced BW change and circulating IGF-I concentrations. Piglet BW change decreased quadratically with fasting. Piglets fasted for 12 h lost an average of 70 g, or 2% of their d 6 BW, whereas piglets fasted for only 6 h before sacrifice maintained a positive weight gain between d 6 and 7. Serum IGF-I decreased linearly with increased fasting time. A 6-h fast resulted in a 16% decrease in serum IGF-I, whereas a 12-h fast resulted in a 34% decrease in serum IGF-I concentrations.

In addition, changes in circulating IGFBP profiles in response to fasting were observed. The IGFBP-4 decreased 31% with a 6-h fast. Although the greatest percentage decrease in IGFBP-4 was observed within 6 h of fasting, IGFBP-4 continued to decrease with additional fasting time. In contrast to IGFBP-4, IGFBP-1 increased with fasting time. Serum IGFBP-1 increased 30% after 6 h and showed a further increase after 12 h of fasting to levels threefold greater than fed (0-h) piglets.

Food restriction over several days has been shown to alter piglet serum IGFBP profiles (McCusker et al., 1991; Zjilstra et al., 1997), but documentation of the effect of short-term food deprivation in livestock is limited, and most fasting studies have been conducted in human subjects (Suikkari et al., 1988). Katz et al. (2002) demonstrated that serum IGFBP-1 increases steadily during fasting, following an inverse relationship with insulin. The increase in IGFBP-1 is thought to serve as a glucose counter-regulatory hormone during fasting and hypoglycemia by binding free IGF-I and inhibiting its ability to bind to IGF receptors. Thus, the response of circulating IGF-I (–34%) and IGFBP-1 (+300%) to fasting illustrates the need to control for postabsorptive state when aspects of the IGF axis are included in the outcome variables.

The gastrointestinal tract often displays striking structural and functional changes to food restriction (Ferraris and Carey, 2000). We observed decreased intestinal weight (g/kg of BW) within 6 h of fasting, whereas a change in overall BW was not detected until after 12 h of food restriction. Although we did not directly measure tissue hydration, we speculate that the change in intestinal weight may reflect short-term changes in tissue wet weight that arise from decreased luminal nutrient transport (Meinild et al., 1998) and blood flow to the tissue (Nowicki et al., 1983; Niinikoski et al., 2004). Glucose and galactose, produced from dietary lactose by the action of LPH, are transported across the brushborder membrane via the sodium-glucose co-transporter. It has been reported that the sodium-glucose co-transporter functions as a molecular water pump, wherein the transmembrane transport of one sugar molecule is coupled with two sodium ions and the influx of 210 water molecules (Meinild et al., 1998). From the serosal side, it was demonstrated in nonanesthetized, awake 2-d-old piglets that within 30 min of feeding, oxygen delivery and oxygen extraction increased by >30% compared with the preprandial state (P < 0.05). The increase in oxygen delivery was a result of an increase in gastrointestinal blood flow, which was localized to the mucosal-submucosal layer of the small intestine (Nowicki et al., 1983). The importance of luminal nutrients to maintain intestinal blood flow was further supported by a recent study in which 3-wk-old piglets were placed on total parenteral nutrition (TPN) for 24 or 48 h (Niinikoski et al., 2004). After 8 h of TPN, portal and superior mesenteric artery blood flow was significantly decreased (–30%) compared with enteral feeding, and flows remained near levels of food-deprived piglets for the remaining 48 h of TPN. Those researchers concluded that the transition from enteral to parenteral nutrition induced a rapid (within 8 h) decrease in intestinal blood flow, which likely preceded the subsequent villus atrophy and suppression of protein synthesis observed at 24 h, and the decreased cell proliferation and cell survival observed after 48 h on TPN (Niinikoski et al., 2004). The time points studied herein, 6 and 12 h, coincide with the period of time of decreased blood flow, but before the onset of villus atrophy.

Despite the decrease in intestinal weight, piglets fasted for 6 or 12 h had 32 and 45% greater villus height than fed piglets, respectively. Increases in mid-villus width, total surface area, and crypt depth also were observed in fasted vs. fed piglets. This result was unexpected, as most studies have shown a decrease in villus height and crypt depth in response to food deprivation (Mayhew, 1987; Carey et al., 1994; Kong et al., 2000); however, the duration of food restriction in these studies was 48 to 72 h. The lack of change in mucosal protein and DNA content with fasting suggests that changes in morphology were not due to alterations in villus cell number, although fasting periods >24 h were associated with decreased cell number along the crypt-villus axis (Raul and von der Decken, 1985). The intestinal brush border architecture is dynamic under physiological conditions including feeding, fasting, or exposure to lectins (Heintzelman and Mooseker, 1992). In support of our observations, data from hamsters, rats, and humans document changes in the volume of individual enterocytes lining the villi in response to feeding (Pappenheimer and Michel, 2003). During sodium-coupled absorption, enterocytes shrink and lose up to 30% of their volume. In hamsters, the average volume of nonabsorbing enterocytes was 1,503 µm³ vs. 1,040 µm³ during the absorption of glucose (Pappenheimer and Michel, 2003). Thus, it is reasonable to speculate that our observed increase in overall villus height and width after 6 to12 h fasting may reflect short-term changes in enterocyte volume during the postabsorptive state.

In contrast to the effect of fasting, no effect of IGF-I on villus morphology was detected. Others have documented improvements in villus architecture in response to oral IGF-I supplementation of artificial formula (Burrin et al., 1996; Houle et al., 1997, 2000); however, this effect has not been observed by all (Alexander and Carey, 1999; Burrin et al., 2001). The different model used in this project (sow-reared) vs. artificial rearing in the previous studies may contribute to this discrepancy. Additionally, other bioactive components in sow milk (Donovan and Odle, 1994) may modulate the actions of IGF-I on villus morphology.

Several previous studies have investigated the effect of enterally administered IGF-I on nutrient transport (Alexander and Carey, 1999, 2001, 2002) and intestinal development (Burrin et al., 1996, 2001) in piglets. A particular focus of our laboratory has been on the effect of IGF-I on intestinal LPH activity (Houle et al., 2000; Park et al., 1999, 2001), and mRNA abundance (Houle et al., 2000), synthesis, and processing (Burrin et al., 2001; Park et al., 2001), all of which were shown to be greater in piglets fed sow milk replacer + IGF-I compared with piglets receiving sow milk replacer alone. The magnitude of increase in LPH activity in response to IGF-I was greater when piglets were killed in a postabsorptive state (Houle et al., 1997, 2000; Park et al., 1999) than when piglets were killed in a fed state (Burrin et al., 2001; Park et al., 2001). The latter two studies involved stable isotope protocols that required piglets receive a continuous infusion of luminal nutrients until immediately before intestinal sample collection (Burrin et al., 2001; Park et al., 2001). The stable isotope enrichment findings suggested that enterally administered IGF-I suppressed intestinal proteolysis and substantially increased the proportion of newly synthesized pro-LPH that was processed and inserted in the brush border membrane (e.g., increased processing efficiency; Burrin et al., 2001). Greater efficiency of insertion of LPH into the brush border may, in turn, affect the turnover rate of LPH, allowing for LPH activity to be maintained at greater levels in the postabsorptive state. Therefore, we wished to assess the effect of duration of food restriction on LPH activity. Piglets suckling TG sows had greater jejunal LPH and SI activities, but no effect of fasting on disaccharidase activity was apparent, despite the observed morphological changes. Nonetheless, simply measuring disaccharidase activity after a fast of only 6 or 12 h might not have been sufficiently sensitive to detect differences in LPH turnover.

In conclusion, using a transgenic model of mammary-specific IGF-I production, we have confirmed that oral IGF-I upregulates jejunal LPH and SI activities, whereas disaccharidase activities were unaffected by a short-term fast. Food deprivation of piglets for as little as 6 to 12 h before euthanasia decreased serum IGF-I concentrations, altered serum IGFBP profiles, and decreased BW and intestinal weight. A unique observation was the marked villus morphological changes in response to short-term fasting, which are counter to what has been reported with longer-term food restriction.

	Implications

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 
Piglets used to investigate gastrointestinal development are frequently food-deprived overnight before euthanasia; however, differences in the duration of food restriction could be a confounding factor when comparing results among experiments. We showed that a short-term fast before sample collection altered intestinal weight, villus morphology, and serum insulin-like growth factor-I and insulin-like growth factor-I binding protein levels compared with the fed state. Therefore, duration of food deprivation before euthanasia should be considered when designing experiments, as the magnitude of differences between the fed and fasted state may exceed those expected as a result of the experimental treatment. In addition, the duration of food restriction before sample collection should be noted in publications to better enable investigators to compare results among experiments.

	Footnotes

 
¹ This research was funded by a grant from the USDA NRICGP (AG-00-35206-9537) and by the State of Illinois through the Illinois Council for Food and Agricultural Research (C-FAR) Sentinel Program.

² Correspondence: 449 Bevier Hall, 905 S. Goodwin Avenue (phone: 217-333-2289; fax: 217-333-9368; e-mail: sdonovan{at}uiuc.edu).

Received for publication July 15, 2004. Accepted for publication July 5, 2005.

	Literature Cited

Top Abstract Introduction Materials and Methods Results Discussion Implications Literature Cited

 


Alexander, A. N., and H. V. Carey. 1999. Oral IGF-I enhances nutrient and electrolyte absorption in neonatal piglet intestine. Am. J. Physiol. 277:G619–G265.

Alexander, A. N., and H. V. Carey. 2001. Involvement of PI 3-kinase in IGF-I stimulation of jejunal Na+-K+-ATPase activity and nutrient absorption. Am. J. Physiol. 280:G222–G228.

Alexander, A. N., and H. V. Carey. 2002. Insulin-like growth factorI stimulates Na+-dependent glutamine absorption in piglet enterocytes. Dig. Dis. Sci. 47:1129–1134.[Medline]

Auldist, D. E., D. Carlson, L. Morrish, C. M. Wakeford, and R. H. King. 2000. The influence of suckling interval on milk production of sows. J. Anim. Sci. 78:2026–2031.[Abstract/Free Full Text]

Burrin, D. G., B. Stoll, M. Z. Fan, M. A. Dudley, S. M. Donovan, and P. J. Reeds. 2001. Oral IGF-I alters the posttranslational processing but not the activity of lactase phlorizin hydrolase in formula-fed neonatal pigs. J. Nutr. 131:2235–2241.[Abstract/Free Full Text]

Burrin, D. G., T. J. Wester, T. A. Davis, S. Amick, and J. P. Heath. 1996. Orally administered IGF-I increases intestinal mucosal growth in formula-fed neonatal pigs. Am. J. Physiol. 270:R1085–1091.

Carey, H. V., U. L. Hayden, and K. E. Tucker. 1994. Fasting alters basal and stimulated ion transport in piglet jejunum. Am. J. Physiol. 267:R156–R163.

Cui, X. L., L. Jiang, and R. P. Ferraris. 2003. Regulation of intestinal GLUT2 mRNA abundance by luminal and systemic factors. Biochem. Biophys. Acta 161:178–185.

Donovan, S. M., J. C.- J. Chao, R. T. Zijlstra, and J. Odle. 1997. Orally administered iodinated recombinant human insulin-like growth factor-I (¹²⁵I-rhIGF-I) is poorly absorbed by the newborn piglet. J. Pediatr. Gastroenterol. Nutr. 24:174–182.[Medline]

Donovan, S. M., M. H. Monaco, G. T. Bleck, J. B. Cook, M. S. Noble, W. L. Hurley, and M. B. Wheeler. 2001. Transgenic over-expression of bovine -lactalbumin and human insulin-like growth factor-I in porcine mammary gland. J. Dairy Sci. 84(E Sup-pl.):E216–E222.[Abstract/Free Full Text]

Donovan, S. M., and J. Odle. 1994. Growth factors in milk as mediators of infant development. Page 147 in Annu. Rev. Nutr. Vol. 14. R. E. Olson, D. M. Bier, and D. B. McCormick, eds. Annual Reviews, Inc., Palo Alto, CA.

Dudley, M. A., F. Jahoor, D. G. Burrin, and P. J. Reeds. 1994. Brush-border disaccharidase synthesis in infant pigs measured in vivo with [²H₃] leucine. Am. J. Physiol. 267:G1128–G1134.

Ferraris, R. P., and H. V. Carey. 2000. Intestinal transport during fasting and malnutrition. Annu. Rev. Nutr. 20:195–219.[Medline]

Goda, T. 2000. Regulation of the expression of carbohydrate digestion/absorption-related genes. Br. J. Nutr. 84(Suppl. 2):S245–S248.

Habold, C., C. Chevalier, S. Dunel-Erb, C. Foltzer-Jourdainne, Y. Le Maho, and J. H. Lignot. 2004. Effects of fasting and refeeding on jejunal morphology and cellular activity in rats in relation to depletion of body stores. Scand. J. Gastroenterol. 39:531–539.[Medline]

Hayden, U. L., and H. V. Carey. 2000. Neural control of intestinal ion transport and paracellular permeability is altered by nutritional status. Am. J. Physiol. 278:R1589–R1594.

Heintzelman, M. B., and M. S. Mooseker. 1992. Assembly of the intestinal brush border cytoskeleton. Curr. Top. Dev. Biol. 26:93–122.[Medline]

Houle, V. M., Y. K. Park, S. C. Laswell, G. G. Freund, M. A. Dudley, and S. M. Donovan. 2000. Investigation of three doses of oral insulin-like growth factor-I on jejunal lactase phlorizin hydrolase activity and gene expression and enterocyte proliferation and migration in piglets. Pediatr. Res. 48:497–503.[Medline]

Houle, V. M., E. A. Schroeder, J. Odle, and S. M. Donovan. 1997. Small intestinal disaccharidase activity and ileal villus height are increased in piglets consuming formula containing recombinant human insulin-like growth factor-I. Pediatr. Res. 42:78–86.[Medline]

Jensen, T., G. Sangel, and B. Algers. 1991. Nursing and sucking behaviour of semi-naturally kept pigs during the first 10 days of post-partum. Appl. Anim. Behav. Sci. 31:195–203.

Katz, L. E., D. D. DeLeon, H. Zhao, and A. F. Jawad. 2002. Free and total insulin-like growth factor (IGF)-I levels decline during fasting: Relationships with insulin and IGF-binding protein-1. J. Clin. Endocrinol. Metab. 87:2978–2983.[Abstract/Free Full Text]

Kong, S. E., J. C. Hall, D. Cooper, and R. D. McCauley. 2000. Starvation alters the activity and mRNA level of glutaminase and glutamine synthetase in the rat intestine. J. Nutr. Biochem. 11:393–400.[Medline]

Martins, M. J., C. Hipolito-Reis, and I. Azevedo. 2001. Effect of fasting on rat duodenal and jejunal microvilli. Clin. Nutr. 20:325–331.[Medline]

Mayhew, T. M. 1987. Quantitative ultrastructural study on the responses of microvilli along the small bowel to fasting. J. Anat. 154:237–243.[Medline]

McCusker, R. H., W. S. Cohick, W. H. Busby, and D. R. Clemmons. 1991. Evaluation of the developmental and nutritional changes in porcine insulin-like growth factor-binding protein-1 and -2 serum levels by immunoassay. Endocrinology 129:2631–2638.[Abstract]

Meinild, A., D. A. Klaerke, D. D. Loo, E. M. Wright, and T. Zeuthen. 1998. The human Na+-glucose cotransporter is a molecular water pump. J. Physiol. 508:15–21.[Abstract/Free Full Text]

Niinikoski, H., B. Stoll, X. Guan, K. Kansagra, B. D. Lambert, J. Stephens, B. Hartmann, J. J. Holst, and D. G. Burrin. 2004. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. J. Nutr. 134:1467–1474.[Abstract/Free Full Text]

Nowicki, P. T., B. S. Stonestreet, N. B. Hansen, A. C. Yao, and W. Oh. 1983. Gastrointestinal blood flow and oxygen consumption in awake newborn piglets: Effect of feeding. Am. J. Physiol. 245:G697–G702.

NRC. 1996. The Guide for the Care and Use of Laboratory Animals. 7th ed. Natl. Acad. Press, Washington, DC.

Pan, X., T. Terada, M. Okuda, and K. Inui. 2004. The diurnal rhythm of intestinal transporters SGLT1 and PEPT1 is regulated by feeding conditions in rats. J. Nutr. 134:2211–2215.[Abstract/Free Full Text]

Pappenheimer, J. R., and C. C. Michel. 2003. Role of villus microcirculation in intestinal absorption of glucose: Coupling of epithelial with endothelial transport. J. Physiol. 553:561–574.[Abstract/Free Full Text]

Park, Y. K., M. A. Dudley, D. G. Burrin, and S. M. Donovan. 2001. Mucosal protein and lactase-phlorizin hydrolase synthesis in parenterally-fed piglets receiving partial enteral nutrition and insulin-like growth factor-I. J. Pediatr. Gastroent. Nutr. 33:189–195.[Medline]

Park, Y. K., M. H. Monaco, and S. M. Donovan. 1999. Enteral insulin-like growth factor-I augments intestinal disaccharidase activity in piglets receiving total parenteral nutrition. J. Pediatr. Gastroent. Nutr. 29:198–206.[Medline]

Peterson, G. L. 1977. A simplification of the protein assay method of Lowry et al. which is generally more applicable. Anal. Biochem. 83:346–356.[Medline]

Raul, F., and A. von der Decken. 1985. Changes in chromatin structure and transcription activity by starvation and dietary sucrose in mature and immature intestinal epithelial cells of the rat. Cell. Mol. Biol. 31:299–304.[Medline]

Shimasaki, S., M. Shimonaka, H. - P. Zhang, and N. Ling. 1991. Isolation and molecular characterization of three novel insulin-like growth factor binding proteins (IGFBP-4, 5, and 6). Page 343 in Modern Concepts of Insulin-like Growth Factors. E. M. Spencer, ed. Elsevier, New York, NY.

Suikkari, A. M., V. A. Koivisto, E. M. Rutanen, H. Yki-Jarvinen, K. L. Karnonen, and M. Seppala. 1988. Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. J. Clin. Endocrinol. Metab. 66:266–272.[Abstract]

Zijlstra, R. T., S. M. Donovan, J. Odle, H. B. Gelberg, B. W. Petschow, and H. R. Gaskins. 1997. Protein-energy malnutrition delays small-intestinal recovery in neonatal pigs infected with rotavirus. J. Nutr. 127:1118–1127.[Abstract/Free Full Text]

This article has been cited by other articles:

				M. Berkeveld, P. Langendijk, H. M. G. van Beers-Schreurs, A. P. Koets, M. A. M. Taverne, and J. H. M. Verheijden Postweaning growth check in pigs is markedly reduced by intermittent suckling and extended lactation J Anim Sci, January 1, 2007; 85(1): 258 - 266. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hartke, J. L. Articles by Donovan, S. M. Search for Related Content PubMed PubMed Citation Articles by Hartke, J. L. Articles by Donovan, S. M.