Roles of Na+/Ca2+exchanger 1 in digestive system physiology and pathophysiology

Liao, Qiushi; Du, Qian; Lou, Jun; Xu, Jingyu; Xie, Rui

doi:10.3748/wjg.v25.i3.287

Cited by 25 publications

(15 citation statements)

References 106 publications

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“…Intestinal basal epithelial cells of small intestine, colon and rectum express Ncx1. Previous reports have shown that Vitamin D enhances Ncx1 gene expression and regulates transmembrane Ca 2+ transport (Liao et al, 2019). In duodenal mucosal epithelium, bicarbonate secretion was regulated by Ncx1 reverse mode activation (Dong et al, 2005).…”

Section: Effects Of Gyp On Protein Expression and Glp-1 Stainingmentioning

confidence: 85%

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

Patibandla

Campbell

Shu

et al. 2020

Preprint

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Glucagon-like peptide 1 (GLP-1) is an incretin hormone produced in gut L-cells, which regulates postprandial glucose-dependent insulin secretion, also known as the incretin effect. GLP-1 secretion may be reduced in type 2 diabetes mellitus, impacting on glycaemic regulation. Thus, methods to enhance endogenous GLP-1 secretion by use of natural GLP-1 secretagogues may improve glucose control in diabetes. Gypenosides (GYP) extracted from the plant Gynostemma Pentaphyllum (Jiaogulan) are known for their glucose-lowering effects both in vitro and in vivo, although their effect on GLP-1 secretion is unknown. Our results showed that GYP enhanced cell viability and significantly upregulated antioxidant gene Nrf2, Cat and Ho-1 expression. GYP did not affect glucokinase expression but downregulated proglucagon gene expression over 24h, although, cellular GLP-1 content was unchanged. Prohormone convertase 1 (Pcsk1) gene expression was unchanged by GYP over 24h, although protein levels were significantly downregulated, while prohormone convertase 2 (Pcsk2) mRNA and protein levels were significantly upregulated. Acute exposure to gypenosides enhanced calcium uptake and GLP-1 release from GLUTag cells both at low and high glucose concentrations. These results suggest that anti-diabetic properties of gypenosides are partly linked to their ability to stimulate GLP-1 secretion. Gypenosides enhance antioxidant gene expression and may protect L-cells from excess oxidative stress.

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Section: Effects Of Gyp On Protein Expression and Glp-1 Stainingmentioning

confidence: 85%

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

Patibandla

Campbell

Shu

et al. 2020

Preprint

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“…The sodium-calcium exchanger (NCX) is a membrane protein within the solute carrier family 8 (SLC8) (Khananshvili, 2013). In humans, the NCX family is involved in cellular Ca 2+ homeostasis in the intestine, heart, skeletal muscle and nervous system (Loffing et al, 2001;On et al, 2008;Khananshvili, 2013;Liao et al, 2019). Currently, three NCX exchangers have been implicated in Ca 2+ transport, NCX1, NCX2 and NCX3 (Khananshvili, 2013).…”

Section: Sodium-calcium Exchangers (Ncx)mentioning

confidence: 99%

Ion Transporters and Osmoregulation in the Kidney of Teleost Fishes as a Function of Salinity

et al. 2021

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Euryhaline teleosts exhibit major changes in renal function as they move between freshwater (FW) and seawater (SW) environments, thus tolerating large fluctuations in salinity. In FW, the kidney excretes large volumes of water through high glomerular filtration rates (GFR) and low tubular reabsorption rates, while actively reabsorbing most ions at high rates. The excreted product has a high urine flow rate (UFR) with a dilute composition. In SW, GFR is greatly reduced, and the tubules reabsorb as much water as possible, while actively secreting divalent ions. The excreted product has a low UFR, and is almost isosmotic to the blood plasma, with Mg2+, SO42–, and Cl– as the major ionic components. Early studies at the organismal level have described these basic patterns, while in the last two decades, studies of regulation at the cell and molecular level have been implemented, though only in a few euryhaline groups (salmonids, eels, tilapias, and fugus). There have been few studies combining the two approaches. The aim of the review is to integrate known aspects of renal physiology (reabsorption and secretion) with more recent advances in molecular water and solute physiology (gene and protein function of transporters). The renal transporters addressed include the subunits of the Na+, K+- ATPase (NKA) enzyme, monovalent ion transporters for Na+, Cl–, and K+ (NKCC1, NKCC2, CLC-K, NCC, ROMK2), water transport pathways [aquaporins (AQP), claudins (CLDN)], and divalent ion transporters for SO42–, Mg2+, and Ca2+ (SLC26A6, SLC26A1, SLC13A1, SLC41A1, CNNM2, CNNM3, NCX1, NCX2, PMCA). For each transport category, we address the current understanding at the molecular level, try to synthesize it with classical knowledge of overall renal function, and highlight knowledge gaps. Future research on the kidney of euryhaline fishes should focus on integrating changes in kidney reabsorption and secretion of ions with changes in transporter function at the cellular and molecular level (gene and protein verification) in different regions of the nephrons. An increased focus on the kidney individually and its functional integration with the other osmoregulatory organs (gills, skin and intestine) in maintaining overall homeostasis will have applied relevance for aquaculture.

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“…NCX was previously reported to be expressed in small intestinal epithelial cells and to function in the forward mode that is involved in the absorption of Ca 2+ into the bloodstream. However, NCX also has a role in GI epithelial anion secretion (125).…”

Section: Ncxmentioning

confidence: 99%

Advances in Ca2+ modulation of gastrointestinal anion secretion and its dysregulation in digestive disorders (Review)

Shan

Ding

et al. 2020

Exp Ther Med

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Intracellular calcium (Ca 2+) is a critical cell signaling component in gastrointestinal (GI) physiology. Cytosolic calcium ([Ca 2+ ] cyt), as a secondary messenger, controls GI epithelial fluid and ion transport, mucus and neuropeptide secretion, as well as synaptic transmission and motility. The key roles of Ca 2+ signaling in other types of secretory cell (including those in the airways and salivary glands) are well known. However, its action in GI epithelial secretion and the underlying molecular mechanisms have remained to be fully elucidated. The present review focused on the role of [Ca 2+ ] cyt in GI epithelial anion secretion. Ca 2+ signaling regulates the activities of ion channels and transporters involved in GI epithelial ion and fluid transport, including Clchannels, Ca 2+-activated K + channels, cystic fibrosis (CF) transmembrane conductance regulator and anion/HCO 3 exchangers. Previous studies by the current researchers have focused on this field over several years, providing solid evidence that Ca 2+ signaling has an important role in the regulation of GI epithelial anion secretion and uncovering underlying molecular mechanisms. The present review is largely based on previous studies by the current researchers and provides an overview of the currently known molecular mechanisms of GI epithelial anion secretion with an emphasis on Ca 2+-mediated ion secretion and its dysregulation in GI disorders. In addition, previous studies by the current researchers demonstrated that different regulatory mechanisms are in place for GI epithelial HCO 3 and Clsecretion. An increased understanding of the roles of Ca 2+ signaling and its targets in GI anion secretion may lead to the development of novel strategies to inhibit GI diseases, including the enhancement of fluid secretion in CF and protection of the GI mucosa in ulcer diseases. Contents 1. Introduction 2. General aspects of GI epithelial anion secretion 3. Ca 2+ modulation of GI epithelial anion secretion 4. Associated GI diseases 5. Conclusion

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Roles of Na⁺/Ca²⁺exchanger 1 in digestive system physiology and pathophysiology

Cited by 25 publications

References 106 publications

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

Effects of gypenosides on enteroendocrine L-cell function and GLP-1 secretion

Ion Transporters and Osmoregulation in the Kidney of Teleost Fishes as a Function of Salinity

Advances in Ca<sup>2+</sup> modulation of gastrointestinal anion secretion and its dysregulation in digestive disorders (Review)

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