Glucagon‐like Peptide 2 Stimulates Intestinal Nutrient Absorption in Parenterally Fed Newborn Pigs

Sangild, Per Torp; Tappenden, Kelly A.; Malo, Christiane; Petersen, Yvette M.; Elnif, Jan; Bartholome, Anne L.; Buddington, Randal K.

doi:10.1097/01.mpg.0000228122.82723.1b

Cited by 55 publications

(52 citation statements)

References 38 publications

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“…Due to fear of NEC, preterm infants are often placed on PN, which reduces intestinal growth and delays development of functions of newborn pigs, including nutrient absorption (23). Although none of the pigs developed clinical signs of NEC during the period of PN, the present findings indicate the source of MEN is an important determinant of GIT characteristics.…”

Section: Discussionmentioning

confidence: 66%

Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

et al. 2008

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Necrotizing enterocolitis (NEC) causes morbidity and mortality among preterm infants and is associated with nutrient malabsorption. Therefore, a preterm pig model that spontaneously develops NEC was used to investigate the relationship between severity of NEC lesions and galactose absorption in vivo and carriermediated glucose absorption by intact mid small intestine. Preterm pigs collected by caesarian section at 92% of gestation received parenteral nutrition with and without minimal enteral nutrition for 48 h before conversion to enteral nutrition with colostrum or an enteral formula. Pigs were killed when symptoms of NEC were observed or after 36 -40 h of enteral nutrition. NEC lesions decreased in vivo absorption of galactose and mannitol by more than 50% and abolished carrier-mediated glucose uptake by tissues with lesions. Moreover, when NEC lesions were restricted to the colon, small intestinal tissues that seemed clinically healthy had decreased in vitro glucose absorption due to reduced uptake via the sodiumdependent glucose transporter with little or no involvement of the apical facilitative glucose carrier. The present findings reveal a direct relationship between the severity of NEC lesions and the magnitude of sugar malabsorption that is detectable before clinical symptoms are evident. (Pediatr Res 63: 382-387, 2008)

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Section: Discussionmentioning

confidence: 66%

Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

et al. 2008

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“…Inadequate intestinal restitution results in breakdown of intestinal integrity and this has been suggested to be a critical step towards the development of NEC in rodents [157]. Other studies have investigated the therapeutic potential of administering factors known to bolster epithelial barrier integrity (i.e., EGF, glucagon-like peptide 2, trefoil factors [7,13,158,159] and some have shown a reduction in disease, although not complete prevention. Further investigation into how the initial epithelial barrier is compromised may lead to new therapeutic factors capable of preventing the initial breakdown of epithelial barrier integrity.…”

Section: Mucosal Immune and Bacterial Defense Systemsmentioning

confidence: 98%

Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

Siggers

Thymann

Boye

et al. 2011

The Journal of Nutritional Biochemistry

105

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“…It is known that endocrine cells can exert biological effects by releasing hormones that can either influence nearby cells directly, enter the bloodstream to act distantly as hormones, or activate nearby vagal and spinal afferent fibres from the neurons within the nodose and dorsal root ganglia, respectively, as well as the enteric neurons (62) . There is an increasing body of evidence to support that systemic application of the gut hormone, GLP-2, leads to up-regulation of SGLT1 expression (63)(64)(65)(66) . While there is one study suggesting that GIP is involved in enhancing SGLT1 expression (67) , no data as yet are available on the potential role of GLP-1 in this process.…”

Section: Communication Between the Chemosensory Endocrine Cells And Amentioning

confidence: 99%

Glucose sensing and signalling; regulation of intestinal glucose transport

et al. 2011

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Epithelial cells lining the inner surface of the intestinal epithelium are in direct contact with a lumenal environment that varies dramatically with diet. It has long been suggested that the intestinal epithelium can sense the nutrient composition of lumenal contents. It is only recently that the nature of intestinal nutrient-sensing molecules and underlying mechanisms have been elucidated. There are a number of nutrient sensors expressed on the luminal membrane of endocrine cells that are activated by various dietary nutrients. We showed that the intestinal glucose sensor, T1R2 + T1R3 and the G-protein, gustducin are expressed in endocrine cells. Eliminating sweet transduction in mice in vivo by deletion of either gustducin or T1R3 prevented dietary monosaccharide-and artificial sweetener-induced up-regulation of the Na + /glucose cotransporter, SGLT1 observed in wild-type mice. Transgenic mice, lacking gustducin or T1R3 had deficiencies in secretion of glucagon-like peptide 1 (GLP-1) and, glucose-dependent insulinotrophic peptide (GIP). Furthermore, they had an abnormal insulin profile and prolonged elevation of postprandial blood glucose in response to orally ingested carbohydrates. GIP and GLP-1 increase insulin secretion, while glucagon-like peptide 2 (GLP-2) modulates intestinal growth, blood flow and expression of SGLT1. The receptor for GLP-2 resides in enteric neurons and not in any surface epithelial cells, suggesting the involvement of the enteric nervous system in SGLT1 up-regulation. The accessibility of the glucose sensor and the important role that it plays in regulation of intestinal glucose absorption and glucose homeostasis makes it an attractive nutritional and therapeutic target for manipulation.Intestine: Glucose sensor: Nutrient: Neuroendocrine: SGLT1The intestinal epithelium is lined with a single layer of epithelial cells that undergoes rapid and continuous renewal. The stem cell located near the base of the crypt of Lieberkühn gives rise to absorptive enterocytes, and three types of secretory cells; mucus producing goblet, Paneth and enteroendocrine. Paneth cells, which secrete antimicrobial peptides, digestive enzymes and growth factors, complete their differentiation at the crypt base. The other three epithelial lineages differentiate during a highly organised upward migration from the crypt to the villus tip where they are extruded into the intestinal lumen (1,2) . This process takes about 2-3 d in most species (3)(4)(5) . Enterocytes constitute the majority (90 %) of cells lining the villus (Fig. 1). They are involved in vectorial transport of nutrients from the lumen of the intestine to the systemic system. These polarised cells possess two distinct membrane domains, the apical (brush border) and basolateral. These membranes differ in structure, function and surface charges (6) ; properties that have facilitated their isolation in pure form as brush-border or basolateral membrane vesicles. Brush-border membrane vesicles have been used frequently for measurements of digestive enzyme...

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Glucagon‐like Peptide 2 Stimulates Intestinal Nutrient Absorption in Parenterally Fed Newborn Pigs

Abstract: 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.

Cited by 55 publications

References 38 publications

Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

Aldohexose Malabsorption in Preterm Pigs Is Directly Related to the Severity of Necrotizing Enterocolitis

Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

Glucose sensing and signalling; regulation of intestinal glucose transport

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