Management of short-bowel syndrome: A survey of unmet educational needs among healthcare providers.

BACKGROUND: Management of short-bowel syndrome with intestinal failure (SBS-IF) is complex and requires a multidisciplinary approach. Because of the rarity of SBS-IF, healthcare professionals (HCPs) often lack clinical experience with the disease and may benefit from education regarding SBS-IF and its management. This study identified unmet educational needs related to the management of patients with SBS-IF. METHODS: This was a prospective, web-based survey (December 2019-January 2020) in which a series of clinical questions were posed to US HCPs after presenting three standardized SBS-IF cases to assess current practice patterns. HCPs were then asked a series of questions to identify potential knowledge gaps and unmet educational needs relating to SBS-IF management. RESULTS: Overall, 558 HCPs completed the survey, with 12%-38% having a formal SBS-IF multidisciplinary team currently available to make treatment decisions within their institution. Clinicians involved in care included gastroenterologists (93%), registered dietitians (79%), gastroenterology nurse practitioners and physician assistants (37%), registered nurses (43%), social workers (45%), and psychologists/psychiatrists (27%). There was underuse of published guidelines and limited understanding of the course of intestinal adaptation. Responses to the clinical scenarios highlighted disparities in SBS-IF care delivery, including diagnosis, management goals, medications prescribed, and nutrition practices. CONCLUSIONS: Future SBS-IF educational interventions for HCPs should aim to improve awareness and understanding of the disease, facilitate timely diagnosis, and standardize management practices to ensure patients receive optimal interdisciplinary care as widely as possible.

GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community.

BACKGROUND: This initiative aims to build a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. METHODS: The Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. Empirical consensus was reached through a series of face-to-face meetings, telephone conferences, and e-mail communications. RESULTS: A 2-step approach for the malnutrition diagnosis was selected, that is, first screening to identify at risk status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among GLIM participants that selected 3 phenotypic criteria (non-volitional weight loss, low body mass index, and reduced muscle mass) and 2 etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least 1 phenotypic criterion and 1 etiologic criterion should be present. Phenotypic metrics for grading severity are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology-related diagnosis categories. CONCLUSIONS: A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The construct should be re-considered every 3-5 years.

Implications of low muscle mass across the continuum of care: a narrative review.

Abnormalities in body composition can occur at any body weight. Low muscle mass is a predictor of poor morbidity and mortality and occurs in several populations. This narrative review provides an overview of the importance of low muscle mass on health outcomes for patients in inpatient, outpatient and long-term care clinical settings. A one-year glimpse at publications that showcases the rapidly growing research of body composition in clinical settings is included. Low muscle mass is associated with outcomes such as higher surgical and post-operative complications, longer length of hospital stay, lower physical function, poorer quality of life and shorter survival. As such, the potential clinical benefits of preventing and reversing this condition are likely to impact patient outcomes and resource utilization/health care costs. Clinically viable tools to measure body composition are needed for routine screening and intervention. Future research studies should elucidate the effectiveness of multimodal interventions to counteract low muscle mass for optimal patient outcomes across the healthcare continuum. Key messages Low muscle mass is associated with several negative outcomes across the healthcare continuum. Techniques to identify and counteract low muscle mass in clinical settings are needed.

Human Milk Oligosaccharides Influence Intestinal Epithelial Cell Maturation In Vitro.

OBJECTIVES: Human milk oligosaccharides (HMOs) are reported to promote epithelial cell differentiation in vitro. The aim of the present study was to assess induction of epithelial cell differentiation by individual and combined administration of 3 HMOs. METHODS: An in vitro epithelial model of the crypt-villus axis consisting of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cells was used. Cultures were randomized to 17 treatments for 72 hours of incubation: low- and high-dose HMOs (3'sialyllactose [3'SL] at 0.2 and 1.0 g/L, 6'siallylactose [6'SL] at 0.4 and 1.0 g/L, and 2'fucosyllactose at 0.2 and 2.0 g/L), HMO combinations at both low and high doses, and controls (culture medium, 4 g/L pooled HMO, and lipopolysaccharide). RESULTS: High doses of individual HMOs (P < 0.05), combined HMOs (P < 0.05), and pooled HMO decreased (P < 0.001) proliferation in preconfluent HT-29 cultures. Pooled means of individual low and high treatments with 3'SL and 6'SL, combinations of 2 or 3 high-dose HMOs, and total HMO significantly reduced (P < 0.05) proliferation in preconfluent Caco-2Bbe cells. HMOs increased differentiation in preconfluent HT-29 and Caco-2Bbe cells. 3'SL and 6'SL increased alkaline phosphatase activity but did not affect disaccharidase activity in postconfluent Caco-2Bbe cells. Apoptosis and necrosis were both decreased (P < 0.001) in postconfluent Caco-2Bbe cells treated with pooled HMO. CONCLUSIONS: HMO treatments inhibited proliferation with some associated enhancement of epithelial differentiation. Effects of HMOs were additive but no specific combinations of HMOs were especially potent. These results suggest that commercially viable individual HMOs and specific combinations may promote intestinal epithelial cell maturation.

Teduglutide-Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome.

BACKGROUND: Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, is available for long-term use by parenteral nutrition (PN)-dependent adults to promote intestinal adaptation but is not approved for use in pediatric patients. The objective of this study was to assess teduglutide-stimulated induced intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation in a neonatal piglet model of short bowel syndrome (SBS). MATERIALS AND METHODS: Neonatal piglets (48 hours old; n = 72) underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment groups, in a 2 × 2 factorial design, with PN or PEN (80% standard PN/20% standard enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received nutrient infusions for 4 hours, 48 hours, or 7 days. RESULTS: Teduglutide improved ( P < .05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon; apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). These effects were complemented and synergistically enhanced by PEN in both site and timing of action. Structural adaptations preceded functional adaptations, but crypt depth remained a strong indicator of adaptation, regardless of time. CONCLUSIONS: The combination of teduglutide and PEN enhances intestinal adaptation beyond that of either therapy alone.

Teduglutide for Safe Reduction of Parenteral Nutrient and/or Fluid Requirements in Adults: A Systematic Review.

BACKGROUND: Teduglutide (Gattex; NPS Pharma, Bedminster, NJ), a recombinant analogue of human glucagon-like peptide 2 (GLP-2), is the first long-term medical therapy approved for the treatment of adults dependent on parenteral nutrition (PN). OBJECTIVE: To assess the efficacy and safety of teduglutide in reducing PN (parenteral nutrient and/or fluid) requirements in PN-dependent adults. METHODS: Studies were identified using predefined search criteria and multiple databases, including Medline and Embase. The search was completed to November 30, 2014, in the absence of date or study design restrictions. Citation inclusion criteria and methodological quality were assessed by 2 independent reviewers. Outcomes of interest were changes in parenteral nutrient or fluid requirements and adverse event incidence. From 2693 unique citations, 76 abstracts were reviewed. Fourteen reports met the inclusion criteria, including data from 2 phase III, double-blind, placebo-controlled clinical trials and their respective extension studies. Data extraction was performed by 2 reviewers using a standardized form. RESULTS: Teduglutide reduced PN requirements compared with placebo, whereas adverse event incidence was similar. LIMITATIONS: Number of subjects studied and length of follow-up. CONCLUSIONS: Teduglutide appears to be a safe and well-tolerated means to reduce PN dependence in adults, regardless of PN dependence duration.

Intestinal adaptation following resection.

Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines.

Stimulation of gastrointestinal tract maturation is 1 of the many benefits of human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are reported to promote enterocyte differentiation in vitro. The objective of this study was to assess the impact of 3 predominant HMOs on multiple aspects of enterocyte maturation in vitro. Ranging from crypt-like to differentiated enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco-2Bbe to model early and late stages of differentiation, respectively. With this model of the crypt-villus axis made up of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto-N-neotetraose (LNnT), 2'-fucosyllactose (2'FL), and 6'-sialyllactose on epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In contrast to previous reports, only treatment with 2'FL at concentrations similar to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29 cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human milk increased transepithelial resistance by 21% (P = 0.002) in well-differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation in an epithelial cell model of the crypt-villus axis. However, effects on differentiation, digestive function, and epithelial barrier function differed between the HMOs tested. These results suggest differential roles for specific HMOs in maturation of the gastrointestinal tract.

Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome.

BACKGROUND: Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells. AIMS: To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation. METHODS: In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32). RESULTS: Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%). CONCLUSIONS: Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.

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

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.

Intestinal adaptation is stimulated by partial enteral nutrition supplemented with the prebiotic short-chain fructooligosaccharide in a neonatal intestinal failure piglet model.

BACKGROUND: Butyrate has been shown to stimulate intestinal adaptation when added to parenteral nutrition (PN) following small bowel resection but is not available in current PN formulations. The authors hypothesized that pre- and probiotic administration may be a clinically feasible method to administer butyrate and stimulate intestinal adaptation. METHODS AND MATERIALS: Neonatal piglets (48 hours old, n = 87) underwent placement of a jugular catheter and an 80% jejunoileal resection and were randomized to one of the following treatment groups: control (20% standard enteral nutrition/80% standard PN), control plus prebiotic (10 g/L short-chain fructooligosaccharides [scFOS]), control plus probiotic (1 × 10(9) CFU Lactobacillus rhamnosus GG [LGG]), or control plus synbiotic (scFOS + LGG). Animals received infusions for 24 hours, 3 days, or 7 days, and markers of intestinal adaptation were assessed. RESULTS: Prebiotic treatment increased ileal mucosa weight compared with all other treatments (P = .017) and ileal protein compared with control (P = .049), regardless of day. Ileal villus length increased in the prebiotic and synbiotic group (P = .011), regardless of day, specifically due to an increase in epithelial proliferation (P = .003). In the 7-day prebiotic group, peptide transport was upregulated in the jejunum (P = .026), whereas glutamine transport was increased in both the jejunum and colon (P = .001 and .003, respectively). CONCLUSIONS: Prebiotic and/or synbiotic supplementation resulted in enhanced structure and function throughout the residual intestine. Identification of a synergistic prebiotic and probiotic combination may enhance the promising results obtained with prebiotic treatment alone.

Emerging therapies for intestinal failure.

Given the immeasurable human distress and health care burden associated with intestinal failure, medical therapies aimed at intestinal rehabilitation are needed. Following massive small-bowel resection, the residual intestine is known to adapt structurally and functionally in an attempt to compensate for the resected portion. However, parenteral nutrition may be associated with many short- and long-term complications, including prevention of intestinal adaptation and promotion of mucosal atrophy due to lack of stimulus provided by oral or enteral nutrition. However, data herein demonstrate that the addition of butyrate, a short-chain fatty acid produced in the colon by dietary fiber fermentation, stimulates intestinal adaptation when added to parenteral nutrition, indicating that current solutions could be formulated to optimize intestinal adaptation and to reduce dependence of individuals with intestinal failure receiving long-term parenteral nutrition regimens.

Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization.

Peripheral activation of the immune system by infectious agents triggers the brain-cytokine system causing sickness behaviors which profoundly impact well-being. Dietary fiber is a beneficial foodstuff that, from a gastrointestinal tract perspective, exists in both insoluble and soluble forms. We show that a diet rich in soluble fiber protects mice from endotoxin-induced sickness behavior by polarizing mice Th2 when compared to a diet containing only insoluble fiber. Mice fed soluble fiber became less sick and recovered faster from endotoxin-induced sickness behaviors than mice fed insoluble fiber. In response to intraperitoneal endotoxin, mice fed soluble fiber had up-regulated IL-1RA and reduced IL-1beta and TNF-alpha in the brain as compared to mice fed insoluble fiber. Importantly, mice fed soluble fiber had a basal increase in IL-4 in the ileum and spleen which was absent in MyD88 knockout mice. Con-A stimulated splenocytes from mice fed soluble fiber showed increased IL-4 and IL-5 and decreased IL-2, IL-12 and IFN-gamma when compared to mice fed insoluble fiber. Likewise, endotoxin-stimulated macrophages from mice fed soluble fiber demonstrated decreased IL-1beta, TNF-alpha, IFN-gamma, IL-12 and nitrate and increased IL-1RA, arginase 1 and Ym1 when compared to mice fed insoluble fiber. Finally, the behavioral protection afforded by feeding mice soluble fiber was reduced in IL-4 knockout mice, as was the impact of soluble fiber on Con-A stimulated splenocytes and endotoxin activated macrophages. These data show that a diet rich in soluble fiber protects against endotoxin-induced sickness behavior by polarizing mice Th2 and promoting alternative activation of macrophages.

Genistein inhibits intestinal cell proliferation in piglets.

Currently 15% of U.S. infants are fed soy formulas that contain up to 14 mg of genistein equivalents/L. Our goal was to investigate the impact of dietary genistein on intestinal development. Piglets (n=8/group) were fed sow milk replacer (MR), MR+1 mg/L of genistein (LG), or MR+14 mg/L of genistein (HG) for 10 d. Formula intake, weight gain, and intestinal length and weight were similar in all groups. Average serum genistein concentration in the HG group was similar to that of soy formula-fed infants. No significant effects of genistein on enterocyte apoptosis, lactase, and sucrase activities or electrophysiologic measures were observed in jejunum or ileum. Jejunal and ileal villus heights were not significantly different, but the percentage of proliferating cell nuclear antigen-positive jejunal crypt cells in the HG was reduced 50% compared with that in MR and LG (p=0.001), indicating decreased proliferation. Enterocyte migration distance in the HG group tended to be 20% less (p=0.1) than LG or MR. Jejunal estrogen receptor beta mRNA expression in HG was half of that in LG (p=0.05), but neither was significantly different from MR. In conclusion, genistein at the level present in soy infant formula is bioactive in the small intestine and results in reduced enterocyte proliferation and migration. The lack of effect of genistein on nutrient transport and enzyme activity suggests that the impact of genistein is greater on proliferating versus differentiated intestinal cells.

Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.

BACKGROUND: Supplementation of total parenteral nutrition (TPN) with a mixture of short-chain fatty acids (SCFA) enhances intestinal adaptation in the adult rodent model. However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific SCFA inducing the intestinotrophic effects and underlying regulatory mechanism(s) are unclear. Therefore, we examined the effect of SCFA supplemented TPN on structural aspects of intestinal adaptation and hypothesized that butyrate is the SCFA responsible for these effects. METHODS: Piglets (n = 120) were randomized to (1) control TPN or TPN supplemented with (2) 60 mmol/L SCFA (36 mmol/L acetate, 15 mmol/L propionate and 9 mmol/L butyrate), (3) 9 mmol/L butyrate, or (4) 60 mmol/L butyrate. Within each group, piglets were further randomized to examine acute (4, 12, or 24 hours) and chronic (3 or 7 days) adaptations. Indices of intestinal adaptation, including crypt-villus architecture, proliferation and apoptosis, and concentration of the intestinotrophic peptide, glucagon-like pepide-2 (GLP-2), were measured. RESULTS: Villus height was increased (p < .029) within 4 hours by supplemented TPN treatments. Supplemented TPN treatments increased (p < .037) proliferating cell nuclear antigen expression along the entire intestine. Indicative of an antiapoptotic profile, jejunal Bax:Bcl-w abundance was decreased (p = .033) by both butyrate-supplemented TPN treatments, and ileal abundance was decreased (p = .0002) by all supplemented TPN treatments, regardless of time. Supplemented TPN treatments increased (p = .016) plasma GLP-2 concentration at all time points. CONCLUSIONS: Butyrate is the SCFA responsible for augmenting structural aspects of intestinal adaptations by increasing proliferation and decreasing apoptosis within 4 hours postresection. The intestinotrophic mechanism(s) underlying butyrate's effects may involve GLP-2. Ultimately, butyrate administration may enable an infant with short-bowel syndrome to successfully transition to enteral feedings by maximizing their absorptive area.

Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story.

The nutritional regulation of intestinal adaptation extends beyond the route of nutrient administration as specific nutrients are known to mediate the adaptive response. Dietary carbohydrates are known to enhance intestinal adaptation in patients with short-bowel syndrome. This review discusses SCFA-induced adaptation in intestinal structure and function in adult rat and neonatal piglet models. Potential mechanisms relate to the salvage of energy as SCFA in the colon, direct mediation of intestinal adaptation by SCFA and stimulated release of glucagon-like peptide-2 (GLP-2) from enteroendocrine L cells by SCFA. Among the produced SCFA, butyrate appears to be responsible for increasing plasma GLP-2 concentration, in addition to the enterotrophic effects. Emerging evidence reveals that physiological concentrations of butyrate acutely upregulate the expression of key enterocyte-associated nutrient transporters. Focused experiments are needed to carefully identify the critical components of intestinal adaptation and yield conclusions regarding the relative contributions of SCFA and GLP-2 during the various phases of this process.

GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1.

BACKGROUND & AIMS: Our aim was to determine whether the intestinotrophic effects of GLP-2 are mediated by acute up-regulation of intestinal substrate utilization in TPN-fed piglets. METHODS: Twenty-four 12-day-old pigs, fitted with a portal flow probe and carotid, jugular and portal catheters, were fed by TPN for 7 days. On day 8, a group of pigs (n = 8) was infused intravenously with saline (control) for 4 hours and then with GLP-2 (500 pmol x kg(-1) x hour(-1), GLP-2) for 4 hours. (2)H-glucose and (13)C-phenylalanine were infused to estimate their kinetics and protein turnover. Another group (n = 8) received consecutive intravenous infusions of saline, GLP-2, and GLP-2 plus N(G)-Nitro-L-arginine methyl ester (L-NAME, 50 micromol x kg(-1) x hour(-1)) for 4 hours each. RESULTS: GLP-2 acutely increased portal-drained visceral (PDV) blood flow rate (+25%) and intestinal blood volume (+51%) in TPN-fed piglets. GLP-2 also increased intestinal constitutive nitric oxide synthase (NOS) activity and endothelial NOS protein abundance. GLP-2 acutely increased PDV glucose uptake (+90%) and net lactate production (+79%). Co-infusion of GLP-2 plus L-NAME did not increase either PDV blood flow rate or glucose uptake. GLP-2 increased PDV indispensable amino acid uptake by 220% and protein synthesis by 125%, but did not decrease protein breakdown or phenylalanine oxidation. CONCLUSIONS: We conclude that in TPN-fed neonatal pigs, GLP-2 acutely stimulates intestinal blood flow and glucose utilization, and this response is nitric oxide-dependent. These findings suggest that GLP-2 may play an important physiological role in the regulation of intestinal blood flow and that nitric oxide is involved in GLP-2 receptor function.

Dietary lipids alter the effect of steroids on transport of glucose after intestinal resection: Part II. Signalling of the response.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. Budesonide (Bud) increases the jejunal D-glucose uptake, and this effect is prevented through a polyunsaturated fatty acid (PUFA) diet. This study was undertaken to assess the possible signalling effect of budesonide, prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids. METHODS: Northern blots were performed. RESULTS: Steroids reduced the jejunal but not the ileal expression of proglucagon. Ornithine decarboxylase (ODC) expression was reduced in the jejunum. CONCLUSIONS: c-jun, ODC, and proglucagon may be involved in the adaptive response that occurs with steroids and variations in dietary lipids after intestinal resection.

Dietary lipids alter the effect of steroids on the transport of glucose after intestinal resection: Part I. Phenotypic changes and expression of transporters.

BACKGROUND/PURPOSE: Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the effect on D-glucose uptake of budesonide (Bud), prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids (PUFA). METHODS: In vitro ring uptake technique, Western blots, and Northern blots were performed. RESULTS: Bud increased the jejunal D-glucose uptake, and this effect was prevented by feeding PUFA. SGLT1 and Na+/K+ ATPase protein and mRNA abundance did not correlate with the change in the rate of uptake of glucose. CONCLUSIONS: (1) Bud increased the jejunal glucose uptake, (2) the activity of the sugar transporter does not correlate with the abundance of protein or their respective mRNAs, (3) th Bud effect on glucose uptake is prevented by feeding PUFA. Thus, the desired intestinal adaptive response after intestinal resection may be enhanced further by the administration of the locally acting steroid budesonide and by feeding a saturated compared with a polyunsaturated fatty acid diet.