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Jens J Holst - One of the best experts on this subject based on the ideXlab platform.

  • glucagon like Peptide 2 inhibits postprandial gallbladder emptying in man a randomized double blinded crossover study
    Clinical and translational gastroenterology, 2020
    Co-Authors: Nina L Hansen, Bolette Hartmann, Andreas Bronden, Christina C Nexoelarsen, Alexander S Christensen, David P Sonne, Jens F Rehfeld, Nicolai Wever J Albretchsen, Tina Vilsboll, Jens J Holst
    Abstract:

    INTRODUCTION A recent study in mice points to the gut-derived hormone Glucagon-Like Peptide 2 (GLP-2) as an important regulator of gallbladder motility inducing gallbladder relaxation and refilling. In this study, we evaluated the effect of exogenous GLP-2 on postprandial gallbladder motility in healthy men. METHODS In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effect of 4-hour intravenous infusions of high-dose GLP-2 (10 pmol × kg × min), low-dose GLP-2 (1 pmol × kg × min), and placebo (saline) on postprandial gallbladder motility. A 300-kcal liquid-mixed meal (added 1.5 g of acetaminophen for indirect measurement of gastric emptying) was served 30 minutes after start of intravenous infusions. Gallbladder volume was assessed by ultrasonography. RESULTS Fifteen healthy men, age 24.3 (22.4-26.1) years (mean [95% confidence interval]) and body mass index 22.5 (21.7-23.4) kg × m, were included. Basal plasma GLP-2 concentration was 14 (11-17) pmol/L. During low-dose and high-dose GLP-2 infusions, steady-state postprandial plasma GLP-2 concentrations amounted to 201 (188-214) and 2,658 (2,443-2,873) pmol/L, respectively, compared with maximum postprandial plasma GLP-2 concentration of 34 (25-44) pmol/L during placebo. Gallbladder emptying (assessed as baseline-subtracted area under the curve for gallbladder volume) was reduced by low-dose GLP-2 (-0.8 [0.7-1.9] L × min, P < 0.0001) and nearly abolished by high-dose GLP-2 (1.3 [-1.7 to 0.01] L × min, P = 0.029) compared to placebo (-2.0 [-2.8 to -1.1] L × min). Compared to placebo, gastric emptying was reduced by high-dose GLP-2 (P = 0.0060 and 0.019), whereas low-dose GLP-2 did not affect gastric emptying (P = 0.13 and 0.85). DISCUSSION Exogenous GLP-2 exerts a dose-dependent inhibitory effect on postprandial gallbladder emptying in healthy men.

  • 1982 p glucagon like Peptide 2 inhibits postprandial gallbladder emptying in healthy male individuals a randomized double blinded placebo controlled study
    Diabetes, 2019
    Co-Authors: Nina L Hansen, Jens J Holst, Bolette Hartmann, Andreas Bronden, Christina C Nexoelarsen, Alexander S Christensen, David P Sonne, Tina Vilsboll, Filip K. Knop
    Abstract:

    A recent study in mice has demonstrated that the gut-derived hormone Glucagon-Like Peptide-2 (GLP-2) may be involved in the regulation of gallbladder motility and induces gallbladder refilling. This study evaluated the effect of exogenous GLP-2 on postprandial gallbladder motility in humans. On three experimental days, 15 young healthy males ([mean±SEM] age 24.3±1.9 years, BMI 22.5±0.9 kg×m -2 , HbA1c 4.8±0.1% (29.3±1.5 mmol/mol)) were subjected to a 3.5-hour 300 kcal mixed liquid meal-test. Continuous 4-hour intravenous infusions of placebo (saline), low-dose GLP-2 (1 pmol×kg -1 ×min -1 ) or high-dose GLP-2 (10 pmol×kg -1 ×min -1 ) were initiated 30 min before meal ingestion. Gallbladder volume was determined by ultrasonography, and gallbladder ejection fraction was calculated. Postprandial maximum gallbladder ejection fraction during saline infusion (76.3±2.8%) was significantly reduced by low-dose GLP-2 (65.5±3.5%, P=0.026) and completely abolished during high-dose GLP-2 infusion (4.0±3.7%, P In conclusion, exogenous GLP-2 dose-dependently inhibits postprandial gallbladder emptying in healthy male subjects. Disclosure N.L. Hansen: None. C.C. Nexoe-Larsen: None. A. Bronden: Other Relationship; Self; AstraZeneca. A.S. Christensen: None. D.P. Sonne: None. B. Hartmann: None. T. Vilsboll: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker9s Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

  • differential action of tgr5 agonists on glp 2 secretion and promotion of intestinal adaptation in a piglet short bowel model
    American Journal of Physiology-gastrointestinal and Liver Physiology, 2019
    Co-Authors: Barbara Stoll, Jens J Holst, Bolette Hartmann, Ignacio R Ipharraguerre, Jason L Robinson, Jose J Pastor, Juan C Marini, Stephanie M Cruz, Oluyinka O Olutoye
    Abstract:

    Therapeutic activation of endogenous Glucagon-Like Peptide 2 (GLP-2) secretion is a promising strategy to improve intestinal adaptation in patients with short bowel syndrome. This study in neonatal...

  • safety and dosing study of glucagon like Peptide 2 in children with intestinal failure
    Journal of Parenteral and Enteral Nutrition, 2017
    Co-Authors: David L Sigalet, Elaine De Heuvel, Bolette Hartmann, Mary Brindle, Dana Boctor, Linda Casey, Bryan J Dicken, Sonia A Butterworth, Vikram Karnik, Jens J Holst
    Abstract:

    BACKGROUND AND AIMS: A Glucagon-Like Peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued. CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

  • jejunal feeding is followed by a greater rise in plasma cholecystokinin Peptide yy glucagon like Peptide 1 and glucagon like Peptide 2 concentrations compared with gastric feeding in vivo in humans a randomized trial
    The American Journal of Clinical Nutrition, 2016
    Co-Authors: J Luttikhold, Jens J Holst, Bolette Hartmann, Klaske Van Norren, Herman Rijna, Nikki Buijs, M Ankersmit, Annemieke C Heijboer, Jeannette Gootjes, Lucas J C Van Loon
    Abstract:

    Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and the associated endocrine response in vivo in humans remains largely unexplored. We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans. In a randomized, crossover study design, 12 healthy young men (mean ± SD age: 21 ± 2 y) received continuous enteral nutrition that contained noncoagulating proteins for 12 h via a nasogastric tube or a nasojejunal tube placed 30-40 cm distal to the ligament of Treitz. Blood samples were collected during the 12-h postprandial period to assess the rise in plasma glucose, amino acid, and gastrointestinal hormone concentrations. No differences were observed in the postprandial rise in circulating plasma amino acid and glucose concentrations between regimens. Jejunal feeding resulted in higher peak plasma insulin concentrations than did gastric feeding (392 ± 53 compared with 326 ± 54 pmol/L, respectively; P <0.05). The postprandial rise in plasma cholecystokinin, Peptide YY (PYY), Glucagon-Like Peptide 1 (GLP-1), and Glucagon-Like Peptide 2 (GLP-2) concentrations was greater after jejunal feeding than after gastric feeding, with higher peak concentrations and a greater postprandial incremental AUC for GLP-1 and cholecystokinin (all P <0.05). Plasma ghrelin concentrations did not differ between regimens. Enteral nutrition with gastric or jejunal feeding in healthy young men results in similar postprandial plasma amino acid and glucose concentrations. However, the endocrine response differs substantially, with higher peak plasma cholecystokinin, PYY, GLP-1, and GLP-2 concentrations being attained after jejunal feeding. This effect may result in an improved anabolic response, greater insulin sensitivity, and an improved intestinotropic effect. Nevertheless, it may also lead to delayed gastric emptying. This trial was registered at trialregister.nl as NTR2801

Per T Sangild - One of the best experts on this subject based on the ideXlab platform.

  • acute effects of the glucagon like Peptide 2 analogue teduglutide on intestinal adaptation in short bowel syndrome
    Journal of Pediatric Gastroenterology and Nutrition, 2014
    Co-Authors: T Thymann, Palle Jeppesen, Barbara J Stoll, Lars Mecklenburg, Douglas G Burrin, Andreas Vegge, Niels Qvist, Thomas Eriksen, Per T Sangild
    Abstract:

    : Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor Glucagon-Like Peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model. Two-day-old pigs were subjected to resection of 50% of the small intestine (distal part), and the remnant intestine was exteriorized on the abdominal wall as a jejunostomy. All pigs were given total parenteral nutrition for 7 days and a single daily injection of the following doses of teduglutide: 0.01 (n = 6), 0.02 (n = 6), 0.1 (n = 5), or 0.2 mg · kg · day (n = 6), and compared with placebo (n = 9). Body weight increment was similar for all 4 teduglutide groups but higher than placebo (P < 0.05). There was a dose-dependent increase in weight per length of the remnant intestine (P < 0.01) and fractional protein synthesis rate in the intestine was increased in the 0.2 mg · kg · day group versus placebo (P < 0.001); however, functional and structural endpoints including activity of digestive enzymes, absorption of enteral nutrients, and immunohistochemistry (Ki67, villin, FABP2, ChgA, and GLP-2R) were not affected by the treatment. Teduglutide induces trophicity on the remnant intestine but has limited acute effects on functional endpoints. Significant effects of teduglutide on gut function may require a longer adaptation period and/or a more frequent administration of the Peptide. In perspective, GLP-2 or its analogues may be relevant to improve intestinal adaptation in pediatric patients with short bowel syndrome.

  • glucagon like Peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007
    Co-Authors: Per T Sangild, Yvette M Petersen, Jan Elnif, Christiane Malo, Mette Schmidt, Randal K Buddington
    Abstract:

    Exogenous Glucagon-Like Peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87–91% of gestation) with GLP-2 (25 nmol·kg−1·day−1 iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol·kg−1·day−1 iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and bru...

  • Glucagon-Like Peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs.
    American journal of physiology. Regulatory integrative and comparative physiology, 2007
    Co-Authors: Per T Sangild, Yvette M Petersen, Jan Elnif, Christiane Malo, Mette Schmidt, Randal K Buddington
    Abstract:

    Exogenous Glucagon-Like Peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis tha...

  • glucagon like Peptide 2 stimulates intestinal nutrient absorption in parenterally fed newborn pigs
    Journal of Pediatric Gastroenterology and Nutrition, 2006
    Co-Authors: Per T Sangild, Kelly A Tappenden, Yvette M Petersen, Jan Elnif, Christiane Malo, Anne L Bartholome, Randal K Buddington
    Abstract:

    Objectives: Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic Peptide Glucagon-Like Peptide 2 (GLP-2), which reduces TPN-associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN. Methods: Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP-2 (25 nmol kg -1 d -1 ; GLP-2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT-1 and GLUT2). Results: Relative to TPN alone, administration of GLP-2 resulted in small intestines that were larger (P < 0.01), had greater abundances of mRNA and protein for SGLT-1, but not for GLUT2, and had higher capacities to absorb nutrients (P < 0.01). Moreover, the intestines of GLP-2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally. Conclusions: Providing GLP-2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.

  • glucagon like Peptide 2 enhances maltase glucoamylase and sucrase isomaltase gene expression and activity in parenterally fed premature neonatal piglets
    Pediatric Research, 2002
    Co-Authors: Yvette M Petersen, Jan Elnif, Per T Sangild
    Abstract:

    Glucagon-Like Peptide 2 Enhances Maltase-Glucoamylase and Sucrase-Isomaltase Gene Expression and Activity in Parenterally Fed Premature Neonatal Piglets

Yvette M Petersen - One of the best experts on this subject based on the ideXlab platform.

  • glucagon like Peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2007
    Co-Authors: Per T Sangild, Yvette M Petersen, Jan Elnif, Christiane Malo, Mette Schmidt, Randal K Buddington
    Abstract:

    Exogenous Glucagon-Like Peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87–91% of gestation) with GLP-2 (25 nmol·kg−1·day−1 iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol·kg−1·day−1 iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and bru...

  • Glucagon-Like Peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs.
    American journal of physiology. Regulatory integrative and comparative physiology, 2007
    Co-Authors: Per T Sangild, Yvette M Petersen, Jan Elnif, Christiane Malo, Mette Schmidt, Randal K Buddington
    Abstract:

    Exogenous Glucagon-Like Peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis tha...

  • glucagon like Peptide 2 stimulates intestinal nutrient absorption in parenterally fed newborn pigs
    Journal of Pediatric Gastroenterology and Nutrition, 2006
    Co-Authors: Per T Sangild, Kelly A Tappenden, Yvette M Petersen, Jan Elnif, Christiane Malo, Anne L Bartholome, Randal K Buddington
    Abstract:

    Objectives: Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic Peptide Glucagon-Like Peptide 2 (GLP-2), which reduces TPN-associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN. Methods: Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP-2 (25 nmol kg -1 d -1 ; GLP-2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT-1 and GLUT2). Results: Relative to TPN alone, administration of GLP-2 resulted in small intestines that were larger (P < 0.01), had greater abundances of mRNA and protein for SGLT-1, but not for GLUT2, and had higher capacities to absorb nutrients (P < 0.01). Moreover, the intestines of GLP-2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally. Conclusions: Providing GLP-2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.

  • glucagon like Peptide 2 enhances maltase glucoamylase and sucrase isomaltase gene expression and activity in parenterally fed premature neonatal piglets
    Pediatric Research, 2002
    Co-Authors: Yvette M Petersen, Jan Elnif, Per T Sangild
    Abstract:

    Glucagon-Like Peptide 2 Enhances Maltase-Glucoamylase and Sucrase-Isomaltase Gene Expression and Activity in Parenterally Fed Premature Neonatal Piglets

  • Glucagon-Like Peptide 2 Enhances Maltase-Glucoamylase and Sucrase-Isomaltase Gene Expression and Activity in Parenterally Fed Premature Neonatal Piglets
    Pediatric Research, 2002
    Co-Authors: Yvette M Petersen, Jan Elnif, Mette Schmidt, Per T Sangild
    Abstract:

    Exogenous Glucagon-Like Peptide 2 (GLP-2) mimics the stimulatory effect of enteral nutrition on intestinal mucosal growth in preterm neonatal pigs. Little is known about its effects on small intestinal function. In this study, we investigated whether the trophic actions of GLP-2 and enteral nutrition are paralleled by effects on small intestinal function. Cesarean-delivered piglets (92% of gestation) were given either a parenteral nutrient infusion [total parenteral nutrition (TPN), n = 7], TPN + human GLP-2 (25 nmol/kg/d, n = 8), or enteral nutrition (ENT, n = 6) for 6 d. Gene expression (mRNA) and activities of lactase phlorizin hydrolase (LPH), maltase-glucoamylase (MGA), sucrase-isomaltase (SI), aminopeptidase N (ApN), and A (ApA) and dipeptidyl peptidase IV (DPP IV) were measured. Both GLP-2 and enteral nutrition increased mucosal weight (+30–40%, p < 0.05) relative to TPN. GLP-2 stimulated jejunal MGA and SI mRNA abundance and activity levels but did not change LPH in parenterally fed pigs ( p < 0.05). Enteral nutrition decreased jejunal LPH and MGA mRNA abundance and activity and increased ileal ApN, ApA, and DPP IV activities relative to TPN ( p < 0.05). We conclude that GLP-2 and enteral nutrition exert different effects on intestinal enzyme function despite similar effects on intestinal growth. In addition, the effects of GLP-2 on intestinal function in these parenterally fed, premature neonatal pigs differed from those previously reported for similarly fed term neonates.

David L Sigalet - One of the best experts on this subject based on the ideXlab platform.

  • safety and dosing study of glucagon like Peptide 2 in children with intestinal failure
    Journal of Parenteral and Enteral Nutrition, 2017
    Co-Authors: David L Sigalet, Elaine De Heuvel, Bolette Hartmann, Mary Brindle, Dana Boctor, Linda Casey, Bryan J Dicken, Sonia A Butterworth, Vikram Karnik, Jens J Holst
    Abstract:

    BACKGROUND AND AIMS: A Glucagon-Like Peptide 2 (GLP-2) analogue is approved for adults with intestinal failure, but no studies of GLP-2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP-2 in children with intestinal failure. METHODS: Native human GLP-2(1-33) was synthesized following good manufacturing practices. In an open-label trial, with parental consent, 7 parenteral nutrition-dependent pediatric patients were treated with subcutaneous GLP-2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. RESULTS: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP-2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP-2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half-life or endogenous GLP-2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP-2 was discontinued. CONCLUSIONS: GLP-2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP-2 release or metabolism. These results suggest that GLP-2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.

  • differential effects on intestinal adaptation following exogenous glucagon like Peptide 2 therapy with and without enteral nutrition in neonatal short bowel syndrome
    Journal of Parenteral and Enteral Nutrition, 2017
    Co-Authors: Abdoulaye Diane, David L Sigalet, Justine M. Turner, Pamela R. Wizzard, Patrick N. Nation, Donna F Vine, Mitsuru Muto, David L Bigam, Paul B Pencharz, Paul W Wales
    Abstract:

    Background: We aim to study the efficacy of exogenously administered Glucagon-Like Peptide 2 (GLP-2) on intestinal adaptation in 2 preclinical models of neonatal short bowel syndrome (SBS) according to remnant intestinal anatomy, with and without ileum. Furthermore, we aim to determine if this adaptive effect was potentiated with enteral nutrition (EN). Methods: Neonatal piglets were block-randomized to 75% mid-intestinal (JI group, retains ileum) or distal-intestinal (JC group, has no ileum) resection or no resection (sham control) and GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets received nutrition support, either 100% parenteral nutrition (PN; 0% EN, n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Adaptation was assessed by morphological and histological changes, as well as RT quantitative polymerase chain reaction of nutrient transporters and tight junctional proteins and fat absorption. Data are analyzed by 3-way analysis of variance (ANOVA) and 2-way ANOVA per EN level....

  • glucagon like Peptide 2 alters bile acid metabolism in parenteral nutrition associated liver disease
    Journal of Parenteral and Enteral Nutrition, 2016
    Co-Authors: Si Mi, David L Sigalet, Pamela R. Wizzard, Diana R. Mager, Jonathan M Curtis, Vera C Mazurak, Justine M. Turner
    Abstract:

    Background: We aim to study the mechanisms underlying our previous finding that exogenous Glucagon-Like Peptide-2 (GLP-2) treatment in a preclinical model of neonatal parenteral nutrition–associated liver disease (PNALD) improves cholestasis. Methods: Neonatal piglets received 17 days of parenteral nutrition (PN) therapy and either saline control (PN/Saline n = 8) or GLP-2 treatment at 11 nmol/kg/d (PN/GLP-2, n = 7). At terminal laparotomy, bile and liver samples were collected. The relative gene expression of enzymes involved in bile acid synthesis, regulation, and transport was measured in liver by reverse-transcriptase quantitative polymerase chain reaction. Bile acid composition in bile was determined using tandem mass spectrometry. Data were analyzed using 1-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA. Results: GLP-2 increased the expression of bile acid export genes: multidrug resistance–associated proteins 2 (MRP2) (P = .002) and 3 (MRP3) (P = .037) over saline control. GLP-2 increased...

  • exogenous glucagon like Peptide 2 improves outcomes of intestinal adaptation in a distal intestinal resection neonatal piglet model of short bowel syndrome
    Pediatric Research, 2014
    Co-Authors: Megha Suri, David L Sigalet, Justine M. Turner, Pamela R. Wizzard, Patrick N. Nation, R. O. Ball, Patricia L Brubaker
    Abstract:

    Exogenous Glucagon-Like Peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome

  • Glucagon-Like Peptide 2 induces vasoactive intestinal polyPeptide expression in enteric neurons via phophatidylinositol 3-kinase-γ signaling
    American journal of physiology. Endocrinology and metabolism, 2012
    Co-Authors: Elaine De Heuvel, Laurie E Wallace, Keith A. Sharkey, David L Sigalet
    Abstract:

    Glucagon-Like Peptide 2 (GLP-2) is an enteroendocrine hormone trophic for intestinal mucosa; it has been shown to increase enteric neuronal expression of vasoactive intestinal polyPeptide (VIP) in ...

Patricia L Brubaker - One of the best experts on this subject based on the ideXlab platform.

  • requirement for the intestinal epithelial insulin like growth factor 1 receptor in the intestinal responses to glucagon like Peptide 2 and dietary fat
    The FASEB Journal, 2020
    Co-Authors: Melanie A Markovic, Arjuna Srikrishnaraj, Derek S Tsang, Patricia L Brubaker
    Abstract:

    The intestinal hormone, Glucagon-Like Peptide-2 (GLP-2), enhances the enterocyte chylomicron production. However, GLP-2 is known to require the intestinal-epithelial insulin-like growth factor-1 receptor (IE-IGF-1R) for its other actions to increase intestinal growth and barrier function. The role of the IE-IGF-1R in enterocyte lipid handling was thus tested in the GLP-2 signaling pathway, as well as in response to a Western diet (WD). IE-IGF-1R knockout (KO) and control mice were treated for 11 days with h(GLY2 )GLP-2 or fed a WD for 18 weeks followed by a duodenal fat tolerance test with C14 -labeled triolein. Human Caco-2BBE cells were treated with an IGF-1R antagonist or signaling inhibitors to determine triglyceride-associated protein expression. The IE-IGF-1R was required for GLP-2-induced increases in CD36 and FATP-4 in chow-fed mice, and for expression in vitro; FATP-4 also required PI3K/Akt. Although WD-fed IE-IGF-1R KO mice demonstrated normal CD36 expression, the protein was incorrectly localized 2h post-duodenal fat administration. IE-IGF-1R KO also prevented the WD-induced increase in MTP and decrease in APOC3, increased jejunal mucosal C14 -fat accumulation, and elevated plasma triglyceride and C14 -fat levels. Collectively, these studies elucidate new roles for the IE-IGF-1R in enterocyte lipid handling, under basal conditions and in response to GLP-2 and WD-feeding.

  • synergy of glucagon like Peptide 2 and epidermal growth factor coadministration on intestinal adaptation in neonatal piglets with short bowel syndrome
    American Journal of Physiology-gastrointestinal and Liver Physiology, 2017
    Co-Authors: C L Levesque, Patricia L Brubaker, Pamela R. Wizzard, Patrick N. Nation, Donna F Vine, Mitsuru Muto, J Koepke, Julang Li, David L Bigam, Justine M. Turner
    Abstract:

    Glucagon-Like Peptide-2 (GLP-2) and epidermal growth factor (EGF) are intestinotrophic, with demonstrated benefit in both animal models and human studies of short bowel syndrome (SBS). The current ...

  • exogenous glucagon like Peptide 2 improves outcomes of intestinal adaptation in a distal intestinal resection neonatal piglet model of short bowel syndrome
    Pediatric Research, 2014
    Co-Authors: Megha Suri, David L Sigalet, Justine M. Turner, Pamela R. Wizzard, Patrick N. Nation, R. O. Ball, Patricia L Brubaker
    Abstract:

    Exogenous Glucagon-Like Peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome

  • glucagon like Peptide 2 increases intestinal lipid absorption and chylomicron production via cd36
    Gastroenterology, 2009
    Co-Authors: Joanne Hsieh, Chris Baker, Christine Longuet, Adriano Maida, Jasmine Bahrami, Elaine Xu, Patricia L Brubaker, Daniel J Drucker, Khosrow Adeli
    Abstract:

    Background & Aims Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-Like Peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production. Methods Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36 −/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting. Results Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [ 3 H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36 −/− mice. Conclusions GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.

  • glucagon like Peptide 2 increases intestinal lipid absorption and chylomicron production via cd36
    Gastroenterology, 2009
    Co-Authors: Joanne Hsieh, Christine Longuet, Adriano Maida, Jasmine Bahrami, Patricia L Brubaker, Daniel J Drucker, Christopher Baker, Khosrow Adeli
    Abstract:

    Background & Aims Excessive postprandial lipemia is a prevalent condition that results from intestinal oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins. Glucagon-Like Peptide-2 (GLP-2) is a gastrointestinal-derived intestinotropic hormone that links nutrient absorption to intestinal structure and function. We investigated the effects of GLP-2 on intestinal lipid absorption and lipoprotein production. Methods Intestinal lipid absorption and chylomicron production were quantified in hamsters, wild-type mice, and Cd36 −/− mice infused with exogenous GLP-2. Newly synthesized apoB48 was metabolically labelled in primary hamster jejunal fragments. Fatty acid absorption was measured, and putative fatty acid transporters were assessed by immunoblotting. Results Human GLP-2 increased secretion of the triglyceride (TG)-rich lipoprotein (TRL)-apoB48 following oral administration of olive oil to hamsters; TRL and cholesterol mass each increased 3-fold. Fast protein liquid chromatography profiling indicated that GLP-2 stimulated secretion of chylomicron/very low-density lipoprotein-sized particles. Moreover, GLP-2 directly stimulated apoB48 secretion in jejunal fragments cultured ex vivo, increased expression of fully glycosylated cluster of differentiation 36/fatty acid translocase (CD36), and induced intestinal absorption of [ 3 H]triolein. The ability of GLP-2 to increase intestinal lipoprotein production was lost in Cd36 −/− mice. Conclusions GLP-2 stimulates intestinal apoB48-containing lipoprotein secretion, possibly through increased lipid uptake, via a pathway that requires CD36. These findings suggest that GLP-2 represents a nutrient-dependent signal that regulates intestinal lipid absorption and the assembly and secretion of TRLs from intestinal enterocytes.