Intestinal function in mice with small bowel growth induced by glucagon-like peptide-2

1997 ◽  
Vol 272 (6) ◽  
pp. E1050-E1058 ◽  
Author(s):  
P. L. Brubaker ◽  
A. Izzo ◽  
M. Hill ◽  
D. J. Drucker
Keyword(s):  
Glucose Transporter ◽  
Intestinal Epithelial ◽  
Multidrug Resistance Gene ◽  
Intestinal Growth ◽  
Glucose Transporter 1 ◽  
Sodium Dependent ◽  
Glucagon Like Peptide ◽  
Small Intestinal ◽  
Glutamyl Transpeptidase

Glucagon-like peptide-2 (GLP-2) stimulates small intestinal growth through induction of intestinal epithelial proliferation. To examine the physiology of GLP-2-induced bowel, mice were treated with GLP-2 (2.5 micrograms) or vehicle for 10 days. Small intestinal weight increased to 136 +/- 2% of controls in GLP-2-treated mice, in parallel with 1.4 +/- 0.1- and 1.9 +/- 0.5-fold increments in duodenal RNA and protein content, respectively (P < 0.05-0.001). Similarly, the activities of duodenal maltase, sucrase, lactase, glutamyl transpeptidase, and dipeptidyl-peptidase IV (215 +/- 28% of controls; P < 0.001) were increased by GLP-2. Oral or duodenal administration of glucose or maltose did not reveal any differences in the ability of GLP-2-treated mice to absorb these nutrients, possibly because of decreases in expression of the glucose transporters sodium-dependent glucose transporter-1 (SGLT-1) and GLUT-2. In contrast, absorption of leucine plus triolein was increased after duodenal administration in GLP-2-treated mice (P < 0.01-0.001). Finally, GLP-2 did not alter other markers of intestinal or pancreatic gene expression, including levels of mRNA transcripts for ornithine decarboxylase, multidrug resistance gene, amylase, proglucagon, proinsulin, and prosomatostatin. Thus induction of intestinal growth by GLP-2 in wild-type mice results in a normal-to-increased capacity for nutrient digestion and absorption in vivo.

scholarly journals Intestinal growth-promoting properties of glucagon-like peptide-2 in mice

1997 ◽  
Vol 273 (1) ◽  
pp. E77-E84 ◽  
Author(s):  
C. H. Tsai ◽  
M. Hill ◽  
S. L. Asa ◽  
P. L. Brubaker ◽  
D. J. Drucker
Keyword(s):  
Cell Proliferation ◽  
Fold Increase ◽  
Crypt Cell ◽  
Saline Control ◽  
Intestinal Epithelial ◽  
Intestinal Growth ◽  
Crypt Cell Proliferation ◽  
Term Administration ◽  
Glucagon Like Peptide

Glucagon-like peptide-2 (GLP-2) has been shown to promote intestinal epithelial proliferation. We studied crypt cell proliferation, enterocyte cell death, and feeding behavior in GLP-2-treated mice. GLP-2 had no effect on food consumption [7.7 +/- 0.3 vs. 8.0 +/- 0.4 g/day, saline (control) vs. GLP-2-treated mice, P = not significant]; however, GLP-2 increased the crypt cell proliferation rate (46.0 +/- 1 vs. 57 +/- 5%, control vs. GLP-2, P < 0.01) and decreased the enterocyte apoptotic rate (5.9 +/- 0.7 vs. 2.8 +/- 0.2% apoptotic cells, control vs. GLP-2, P < 0.05) in small bowel (SB) epithelium. GLP-2 induced a significant increase in SB weight (1.3- to 1.75-fold increase over control, P < 0.05 to P < 0.001) in mice 1-24 mo of age. Increased SB weight was maintained after daily administration of GLP-2 to mice for 12 wk, and cessation of GLP-2 administration in older mice led to regression of (increased) SB weight and mucosal height. These observations suggest that GLP-2 regulates both cell proliferation and apoptosis and promotes intestinal growth after both short- and long-term administration in vivo.

Glucagon-like peptide-2 protects against TPN-induced intestinal hexose malabsorption in enterally refed piglets

2006 ◽  
Vol 290 (2) ◽  
pp. G293-G300 ◽  
Author(s):  
J. J. Cottrell ◽  
B. Stoll ◽  
R. K. Buddington ◽  
J. E. Stephens ◽  
L. Cui ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Absorption ◽  
Glucose Transporter 1 ◽  
Portal Vein Flow ◽  
Glucose Transporter 2 ◽  
Glucagon Like Peptide ◽  
Portal Veins

Premature infants receiving chronic total parenteral nutrition (TPN) due to feeding intolerance develop intestinal atrophy and reduced nutrient absorption. Although providing the intestinal trophic hormone glucagon-like peptide-2 (GLP-2) during chronic TPN improves intestinal growth and morphology, it is uncertain whether GLP-2 enhances absorptive function. We placed catheters in the carotid artery, jugular and portal veins, duodenum, and a portal vein flow probe in piglets before providing either enteral formula (ENT), TPN or a coinfusion of TPN plus GLP-2 for 6 days. On postoperative day 7, all piglets were fed enterally and digestive functions were evaluated in vivo using dual infusion of enteral (13C) and intravenous (2H) glucose, in vitro by measuring mucosal lactase activity and rates of apical glucose transport, and by assessing the abundances of sodium glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2). Both ENT and GLP-2 pigs had larger intestine weights, longer villi, and higher lactose digestive capacity and in vivo net glucose and galactose absorption compared with TPN alone. These endpoints were similar in ENT and GLP-2 pigs except for a lower intestinal weight and net glucose absorption in GLP-2 compared with ENT pigs. The enhanced hexose absorption in GLP-2 compared with TPN pigs corresponded with higher lactose digestive and apical glucose transport capacities, increased abundance of SGLT-1, but not GLUT-2, and lower intestinal metabolism of [13C]glucose to [13C]lactate. Our findings indicate that GLP-2 treatment during chronic TPN maintains intestinal structure and lactose digestive and hexose absorptive capacities, reduces intestinal hexose metabolism, and may facilitate the transition to enteral feeding in TPN-fed infants.

scholarly journals Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. R1965-R1971 ◽  
Author(s):  
C. I. Cheeseman
Keyword(s):  
Intracellular Signaling ◽  
Time Course ◽  
Glucose Transporter ◽  
Membrane Vesicles ◽  
Peptide Hormone ◽  
Affinity Constant ◽  
Glucose Transporter 1 ◽  
Intracellular Signaling Pathway ◽  
Sodium Dependent

The effect of in vivo infusion of the peptide hormone glucagon-like peptide 2 (GLP-2) on glucose transport across the rat jejunal brush-border membrane (BBM) was assessed using isolated membrane vesicles. A 2-h infusion of GLP-2 produced a marked acceleration of sodium-dependent glucose uptake into BBM vesicles with a significant overshoot. There was no change in vesicle space or permeability resulting from the hormone infusion. Kinetic analysis showed this stimulation to be the result of a threefold increase in the maximal rate of transport, with no consistent change in the affinity constant ( K m). The time course of this response showed that the effect was observable, but smaller, after only 30 min of hormone infusion and was maximal after 1 h. Sodium-dependent phloridzin binding to the membrane vesicles showed a parallel increase in maximal binding after 1 and 2 h of hormone infusion. Western blotting showed a similar increase in sodium-dependent glucose transporter 1 (SGLT-1) abundance. The effect of GLP-2 could be blocked by luminal brefeldin A or wortmannin. These results indicate that GLP-2 is able to induce trafficking of SGLT-1 from an intracellular pool into the BBM within 60 min and that phosphoinositol 3-kinase may well be involved in the intracellular signaling pathway in this response.

scholarly journals Porcine small intestinal organoids as a model to explore ETEC–host interactions in the gut

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Bjarne Vermeire ◽  
Liara M. Gonzalez ◽  
Robert J. J. Jansens ◽  
Eric Cox ◽  
Bert Devriendt
Keyword(s):  
Intestinal Epithelial ◽  
Gut Health ◽  
Functional Responses ◽  
Host Pathogen Interactions ◽  
Epithelial Surface ◽  
Host Interactions ◽  
Intestinal Organoids ◽  
Host Pathogen ◽  
Small Intestinal

AbstractSmall intestinal organoids, or enteroids, represent a valuable model to study host–pathogen interactions at the intestinal epithelial surface. Much research has been done on murine and human enteroids, however only a handful studies evaluated the development of enteroids in other species. Porcine enteroid cultures have been described, but little is known about their functional responses to specific pathogens or their associated virulence factors. Here, we report that porcine enteroids respond in a similar manner as in vivo gut tissues to enterotoxins derived from enterotoxigenic Escherichia coli, an enteric pathogen causing postweaning diarrhoea in piglets. Upon enterotoxin stimulation, these enteroids not only display a dysregulated electrolyte and water balance as shown by their swelling, but also secrete inflammation markers. Porcine enteroids grown as a 2D-monolayer supported the adhesion of an F4+ ETEC strain. Hence, these enteroids closely mimic in vivo intestinal epithelial responses to gut pathogens and are a promising model to study host–pathogen interactions in the pig gut. Insights obtained with this model might accelerate the design of veterinary therapeutics aimed at improving gut health.

Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats

1997 ◽  
Vol 273 (4) ◽  
pp. E815-E820 ◽  
Author(s):  
Kirk D. Fischer ◽  
Savita Dhanvantari ◽  
Daniel J. Drucker ◽  
Patricia L. Brubaker
Keyword(s):  
Experimental Diabetes ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Villus Height ◽  
Intestinal Growth ◽  
Glucagon Like Peptide ◽  
Small Intestinal ◽  
The Relationship ◽  
Intestinal Weight

Glucagon-like peptide 2 (GLP-2) has recently been identified as a novel intestinal growth factor. Because experimental diabetes is associated with bowel growth, we examined the relationship between GLP-2 and intestinal growth in rats made diabetic by streptozotocin (STZ) injection and treated with or without insulin for 3 wk. Ileal concentrations of the intestinal proglucagon-derived peptides, i.e., glicentin + oxyntomodulin, and GLPs 1 and 2, were increased by 57 ± 20% above those of controls in untreated STZ diabetes ( P < 0.05–0.001). Similar increases in plasma concentrations of glicentin + oxyntomodulin (77 ± 15% above controls, P < 0.01) and GLP-2 (91 ± 32% above controls, P < 0.05) were seen in untreated STZ diabetes. Both wet and dry small intestinal weight increased by 74 ± 20% above controls ( P < 0.01) in STZ diabetes, and macromolecular analysis indicated parallel increases in both protein ( P < 0.001) and lipid ( P < 0.05) content. Villus height ( P < 0.001) and crypt depth ( P < 0.01) were also increased in untreated diabetic rat intestine. Insulin therapy prevented the changes in plasma GLP-2 and intestinal mass seen in untreated STZ diabetes. Thus STZ diabetes is associated with both increased production of GLP-2 and enhanced bowel weight, thereby suggesting a role for GLP-2 in diabetes-associated bowel growth.

Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis

2020 ◽  
Vol 99 (8) ◽  
pp. 977-986
Author(s):  
H. Ida-Yonemochi ◽  
K. Otsu ◽  
H. Harada ◽  
H. Ohshima
Keyword(s):  
Organ Culture ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Maturation Stage ◽  
Sodium Dependent ◽  
Tooth Morphogenesis

Glucose is an essential source of energy for mammalian cells and is transported into the cells by glucose transporters. There are 2 types of glucose transporters: one is a passive glucose transporter, GLUT ( SLC2A), and the other is a sodium-dependent active glucose transporter, SGLT ( SLC5A). We previously reported that the expression of GLUTs during tooth development is precisely and spatiotemporally controlled and that the glucose uptake mediated by GLUT1 plays a crucial role in early tooth morphogenesis and tooth size determination. This study aimed to clarify the localization and roles of SGLT1 and SGLT2 in murine ameloblast differentiation by using immunohistochemistry, immunoelectron microscopy, an in vitro tooth organ culture experiment, and in vivo administration of an inhibitor of SGLT1/2, phloridzin. SGLT1, which has high affinity with glucose, was immunolocalized in the early secretory ameloblasts and the ruffle-ended ameloblasts in the maturation stage. However, SGLT2, which has high glucose transport capacity, was observed in the stratum intermedium, papillary layer, and ameloblasts at the maturation stage and colocalized with Na+-K+-ATPase. The inhibition of SGLT1/2 by phloridzin in the tooth germs induced the disturbance of ameloblast differentiation and enamel matrix formation both in vitro (organ culture) and in vivo (mouse model). The expression of SGLT1 and SGLT2 was significantly upregulated in hypoxic conditions in the ameloblast-lineage cells. These findings suggest that the active glucose uptake mediated by SGLT1 and SGLT2 is strictly regulated and dependent on the intra- and extracellular microenvironments during tooth morphogenesis and that the appropriate passive and active glucose transport is an essential event in amelogenesis.

Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor

2015 ◽  
Vol 12 (2) ◽  
pp. 101-110 ◽  
Author(s):  
Pablo Lapuerta ◽  
Brian Zambrowicz ◽  
Paul Strumph ◽  
Arthur Sands
Keyword(s):  
Glucose Transporter ◽  
Glucose Transporter 1 ◽  
Sodium Dependent

Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2

2003 ◽  
Vol 81 (11) ◽  
pp. 1005-1012 ◽  
Author(s):  
Patricia L Brubaker ◽  
Younes Anini
Keyword(s):  
Biological Activity ◽  
Intestinal Epithelial ◽  
Intestinal Growth ◽  
Pancreatic Glucagon ◽  
The Past ◽  
L Cells ◽  
Peptide Family ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

The proglucagon-derived peptide family consists of three highly related peptides, glucagon and the glucagon-like peptides GLP-1 and GLP-2. Although the biological activity of glucagon as a counter-regulatory hormone has been known for almost a century, studies conducted over the past decade have now also elucidated important roles for GLP-1 as an antidiabetic hormone, and for GLP-2 as a stimulator of intestinal growth. In contrast to pancreatic glucagon, the GLPs are synthesized in the intestinal epithelial L cells, where they are subject to the influences of luminal nutrients, as well as to a variety of neuroendocrine inputs. In this review, we will focus on the complex integrative mechanisms that regulate the secretion of these peptides from L cells, including both direct and indirect regulation by ingested nutrients.Key words: GLP-1, GLP-2, intestine, secretion, nutrients, neural.

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