glucagon-like-peptide-2 and Liver-Diseases

Short-bowel syndrome (SBS) is defined as a state of malabsorption after resection or loss of a major portion of the bowel due to congenital or acquired factors. This article presents an overview on the recent management of pediatric SBS. The pediatric SBS population is very heterogeneous. The incidence of SBS is estimated to be 24.5 per 100,000 live births. The nutritional, medical, and surgical therapies available require a comprehensive evaluation. Thus, multidisciplinary intestinal rehabilitation programs (IRPs) are necessary for the management of these complex patients. The key points of focus in IRP management are hepato-protective strategies to minimize intestinal failure-associated liver disease; the aggressive prevention of catheter-related bloodstream infections; strategic nutritional supply to optimize the absorption of enteral calories; and the management and prevention of small bowel bacterial overgrowth, nephrocalcinosis, and metabolic bone disease. As the survival rate of children with SBS currently exceeds 90%, the application of small bowel transplantation has been evolving. The introduction of innovative treatments, such as combined therapy of intestinotrophic hormones, including glucagon-like peptide-2, may lead to further improvements in patients' quality of life.

Topics: Age Factors; Bone Diseases, Metabolic; Child, Preschool; Female; Glucagon-Like Peptide 2; Humans; Incidence; Infant; Infant, Newborn; Intestinal Failure; Intestine, Small; Liver Diseases; Male; Nephrocalcinosis; Quality of Life; Short Bowel Syndrome

Parenteral nutrition-associated liver disease (PNALD) remains a significant cause of morbidity and mortality in neonates with intestinal failure. Although glucagon-like peptide-2 (GLP-2) is being advanced as therapy, the effect of GLP-2 treatment on PNALD is unknown. We aim to investigate the effect of exogenous GLP-2 administration on hepatic function in a neonatal piglet model of PNALD.. Neonatal piglets (aged 2-6 days) underwent jugular venous catheterization to receive isonitrogenous, isocaloric parenteral nutrition (PN). Piglets were allocated to 2 groups: group 1 (n = 8) received saline while group 2 (n = 7) received GLP-2 (at 11 nmol/kg/d). After 17 days, piglets underwent terminal laparotomy, and bile flow was measured. Liver specimens were analyzed histologically and with immunoperoxidase staining. Age-matched sow-reared control piglets (group 3, n = 8) were used for comparison.. Both groups 1 and 2 receiving PN developed cholestasis relative to sow-reared controls, as evidenced by a decrease in bile flow and increase in serum total bilirubin. However, group 2 had improved bile flow (1.35 vs 0.73 µL/g; P = .02) and diminished bilirubin (38.0 vs 78.5 µmol/L; P = .008) compared with group 1. Group 2 also had lower serum alanine aminotransferase levels, a marker of liver injury. Histologically, the liver specimens in group 1 had marked hepatocyte pigmentation, which was decreased in group 2 specimens.. The exogenous administration of GLP-2 is associated with the improvement of cholestasis and liver injury. This study introduces a novel role for GLP-2 in improving PNALD in the setting of prolonged PN duration.

Topics: Alanine Transaminase; Animals; Animals, Newborn; Bilirubin; C-Reactive Protein; Cholestasis; Female; Glucagon-Like Peptide 2; Liver; Liver Diseases; Male; Organ Size; Parenteral Nutrition; Swine

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.. 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.. 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 expression of Farnesoid X receptor (FXR) (P < .001) and CYP7A1 (cytochrome P450, family 7, subfamily A, polypeptide 1) (P = .03). GLP-2 treatment was associated with decreased concentrations of taurohyocholic acid and conjugates of toxic lithocholic acid (P < .01). GLP-2 treatment increased the liver bile acid content.. GLP-2 treatment was associated with alterations in the hepatic expression of genes involved in bile acid metabolism. The transcriptomic results indicate the mechanisms at the transcriptional level acting to regulate bile acid synthesis and increase bile acid export. Differences in bile acid profiles further support a beneficial role for GLP-2 therapy in PNALD.

Topics: Animals; Animals, Newborn; Bile Acids and Salts; Cholestasis; Cholesterol 7-alpha-Hydroxylase; Disease Models, Animal; Gene Expression Regulation; Glucagon-Like Peptide 2; Lithocholic Acid; Liver Diseases; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Parenteral Nutrition; Swine; Tandem Mass Spectrometry; Transcriptome