scholarly journals Intra-Amniotic Administration of l-Glutamine Promotes Intestinal Maturation And Enteroendocrine Stimulation In Chick Embryos

Author(s):  
Naama Reicher ◽  
Tal Melkman-Zehavi ◽  
Jonathan Dayan ◽  
Zehava Uni

Abstract Initial nutritional stimulation is a key driving force for small intestinal maturation, and is mediated by enteroendocrine L-cells signaling. In chick embryos, administration of specific nutrients into the amniotic fluid stimulates early development of the small intestine. In this study, we examined the effects of intra-amniotic administration of l-glutamine (Gln) on enterocyte morphological and functional maturation and L-cell signaling before and after hatch. Gln stimulation at embryonic day 17 caused an increase in enterocyte and microvilli dimensions by 10 and 20%, respectively, within 48h. Post-hatch, enterocytes and microvilli were 20% longer in Gln-treated chicks. Correspondingly, mRNA expression of brush border nutrient transporters PepT-1 and SGLT-1 and tight junction proteins TJP-1, TJP-2 and Occludin was significantly upregulated before and after hatch (P<0.05) in Gln-treated chicks. We then evaluated the effects of Gln stimulation on enteroendocrine signaling by locating L-cells in the developing jejunum and observed significant increases in mRNA expression of L-cell signaling components GLP-2R, IGF-1 and IGF-1R before and after hatch, in response to Gln stimulation (P<0.05). Our findings link primary nutrient stimulation of L-cells to enterocyte morphological and functional maturation and provide a model for investigating the effects of specific nutrients on enteroendocrine signaling in the developing small intestine.

2009 ◽  
Vol 297 (4) ◽  
pp. G663-G671 ◽  
Author(s):  
Tohru Hira ◽  
Taisuke Mochida ◽  
Kyoko Miyashita ◽  
Hiroshi Hara

Glucagon-like peptide-1 (GLP-1) is released from enteroendocrine cells (L cells) in response to food ingestion. The mechanism by which dietary peptides stimulate GLP-1 secretion in the gut is unknown. In the present study, we found that a hydrolysate prepared from zein, a major corn protein [zein hydrolysate (ZeinH)], strongly stimulates GLP-1 secretion in enteroendocrine GLUTag cells. Stimulatory mechanisms of GLP-1 secretion induced by ZeinH were investigated in the rat small intestine under anesthesia. Blood was collected through a portal catheter before and after ZeinH administration into different sites of the small intestine. The duodenal, jejunal, and ileal administration of ZeinH induced dose-dependent increases in portal GLP-1 concentration. GLP-1 secretion in response to the ileal administration of ZeinH was higher than that in the duodenal or jejunal administration. Capsaicin treatment on esophageal vagal trunks abolished the GLP-1 secretion induced by duodenal ZeinH but did not affect the secretion induced by jejunal or ileal ZeinH. These results suggest that ZeinH in the jejunum or ileum directly stimulates GLP-1 secretion but duodenal ZeinH indirectly stimulates GLP-1 secretion via the vagal afferent nerve. A direct blood sampling method from the duodenal vein and ileal mesenteric vein revealed that ZeinH administered into the ligated duodenal loop enhanced GLP-1 concentration in the ileal mesenteric vein but not in the duodenal vein. This confirmed that ZeinH in the duodenum induces GLP-1 secretion from L cells located in the ileum by an indirect mechanism. These results indicate that a potent GLP-1-releasing peptide, ZeinH, induces GLP-1 secretion by direct and indirect mechanisms in the rat intestine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rune E. Kuhre ◽  
Ida M. Modvig ◽  
Sara L. Jepsen ◽  
Hüsün S. Kizilkaya ◽  
Cecilie Bæch-Laursen ◽  
...  

The molecular sensors underlying nutrient-stimulated GLP-1 secretion are currently being investigated. Peripheral administration of melanocortin-4 receptor (MC4R) agonists have been reported to increase GLP-1 plasma concentrations in mice and humans but it is unknown whether this effect results from a direct effect on the GLP-1 secreting L-cells in the intestine, from other effects in the intestine or from extra-intestinal effects. We investigated L-cell expression of MC4R in mouse and human L-cells by reanalyzing publicly available RNA sequencing databases (mouse and human) and by RT-qPCR (mouse), and assessed whether administration of MC4R agonists to a physiologically relevant gut model, isolated perfused mouse and rat small intestine, would stimulate GLP-1 secretion or potentiate glucose-stimulated secretion. L-cell MC4R expression was low in mouse duodenum and hardly detectable in the ileum and MC4R expression was hardly detectable in human L-cells. In isolated perfused mouse and rat intestine, neither intra-luminal nor intra-arterial administration of NDP-alpha-MSH, a potent MC4R agonist, had any effect on GLP-1 secretion (P ≥0.98, n = 5–6) from the upper or lower-half of the small intestine in mice or in the lower half in rats. Furthermore, HS014—an often used MC4R antagonist, which we found to be a partial agonist—did not affect the glucose-induced GLP-1 response in the rat, P = 0.62, n = 6). Studies on transfected COS7-cells confirmed bioactivity of the used compounds and that concentrations employed were well within in the effective range. Our combined data therefore suggest that MC4R-activated GLP-1 secretion in rodents either exclusively occurs in the colon or involves extra-intestinal signaling.


2012 ◽  
Vol 93 (1) ◽  
pp. 360-365 ◽  
Author(s):  
Min Yao ◽  
Menghong Dai ◽  
Zhaoying Liu ◽  
Wenlong Cui ◽  
Daoyuan Li ◽  
...  

Development ◽  
1982 ◽  
Vol 72 (1) ◽  
pp. 269-286
Author(s):  
N. G. Laing

Counts were made of the number of motoneurons innervating the hind limbs of 10-day normal and paralysed chick embryos whose right hind limb buds had been subjected to varying degrees of amputation prior to innervation. The number of motoneurons on the intact sides of the paralysed embryos was found to be similar to the number present in normal embryos prior to the major period of motoneuron death. Since it has previously been shown that paralysis does not increase the number of motoneurons generated, this means that normal motoneuron death was largely prevented in the paralysed embryos. There were differences in the distributions of motoneurons in the rostrocaudal axis of the spinal cord between normal and paralysed embryos. Therefore, cell death does not eliminate a uniform fraction of motoneurons throughout the rostrocaudal extent of the chick embryo lumbar lateral motor column. It is also argued that there are differences in the relative contribution of the various lumbosacral levels to different parts of the limb, e.g. the shank, before and after the period of cell death. In both normal and paralysed embryos there was a linear relationship between the volume of limb muscle which developed after amputation and the number of motoneurons surviving in the spinal cord. There was no evidence of a ‘compression’ of motoneurons into the remaining muscle either after amputation alone or after amputation combined with paralysis. Motoneurons are therefore rigidly specified for certain parts of the limb. The relationship between motoneuron number and muscle volume on the amputated side differed from that of the intact side. For a similar increase in muscle volume there was a smaller increase in motoneuron number on the intact sides. This suggested a parallel to the paradoxically small increase in motoneuron number that occurs on the addition of a supernumerary limb.


1980 ◽  
Vol 29 (2) ◽  
pp. 383-389
Author(s):  
Yasuhiko Ito ◽  
Hiizu Aoki ◽  
Yoshinobu Kimura ◽  
Michiko Takano ◽  
Koichiro Maeno ◽  
...  

When spleen cells derived from C57BL/6 mice immunized with L cells 7 days previously were cocultured with antigenic cells, immune interferon appeared in the culture fluid. We analyzed the tissue distribution of the immune interferon-producing cells (IIPC) which appeared in various lymphoid organs after allogeneic stimulation. Although fluid from cocultures of L-cell-sensitized thymocytes and L-cells could not detect interferon activity consistently, small numbers of IIPC could be detected by using the enumeration method of IIPC. The generation, maintenance, and nature of IIPC emerging in the spleen were different depending on how the host mice were immunized. Multiple antigenic stimulations were more effective and induced longer-lasting immune interferon production than a single stimulation. IIPC induced by a single stimulation appeared to be sensitive to cortisone, vinblastine, and cyclophosphamide and were relatively short lived. In contrast, IIPC induced by multiple stimulations seemed to be partially resistant to these drugs and long lived. When mice were immunized with intact L-cells, carrageenan, a known antimacrophage agent, had no effect on immune interferon production. However, when mice were immunized with solubilized L-cell antigen, this drug displayed a suppressive effect on immune interferon production.


1999 ◽  
Vol 91 (6) ◽  
pp. 1844-1844 ◽  
Author(s):  
Valerie E. Armstead ◽  
Irina L. Opentanova ◽  
Alexander G. Minchenko ◽  
Allan M. Lefer

Background Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation that has been shown to have a role in the pathophysiology of sepsis and reperfusion injury. The purpose of this study was to investigate TF expression in vital organs and to determine possible regulatory mechanisms of TF expression in the lung during traumatic shock in rats. Methods Noble-Collip drum trauma was induced in anesthetized Sprague-Dawley rats. Anesthetized rats without trauma served as controls. TF activity was measured in plasma and lung tissue. TF messenger RNA (mRNA) was measured in the lung, liver, and small intestine using ribonuclease protection assays. Electromobility shift assays were used to quantify binding of nuclear extracts from lung to TF-specific consensus domains for transcription factors NF-kappaB and AP-1. Results TF activity in plasma increased up to 14-fold and +232% in the lung (P &lt; 0.001 for plasma and lung) 2 h after trauma. TF mRNA level was significantly increased in the lungs (P &lt; 0.01), small intestine (P &lt; 0.01), and liver (P &lt; 0.05) 1 h after trauma compared to sham-operated control rats. TF mRNA expression continued to increase in the lungs and the liver (both, P &lt; 0.001) 2 h after trauma TF sequence-specific complex binding to AP-1 and NF-kappaB domains was enhanced in the lungs of trauma rats (+395%, P &lt; 0.001 and +168%, P &lt; 0.001, respectively). Conclusions These results suggest that TF may play an important role in the pathophysiology of severe trauma and that regulatory elements AP-1 and NF-kappaB may be involved in the regulation of TF mRNA expression in traumatic shock.


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