Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca 2+ entry mechanisms
| العنوان: | Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca 2+ entry mechanisms |
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| المؤلفون: | Fenglian Zhang, Hui Dong, Fenglan Chu, Hanxing Wan, Cheng Lu, Jun Chen |
| المصدر: | British Journal of Pharmacology. 178:346-362 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Pharmacology, Ussing chamber, ORAI1, Chemistry, Ryanodine receptor, Sodium, Glucose uptake, chemistry.chemical_element, STIM1, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, cardiovascular system, Cotransporter, Calcium-induced calcium release, 030217 neurology & neurosurgery |
| الوصف: | BACKGROUND AND PURPOSE Luminal glucose enhances intestinal Ca2+ absorption through apical Cav 1.3 channels necessary for GLUT2-mediated glucose absorption. As these reciprocal mechanisms are not well understood, we investigated the regulatory mechanisms of intestinal [Ca2+ ]cyt and SGLT1-mediated Na+ -glucose co-transports. EXPERIMENTAL APPROACH Glucose absorption and channel expression were examined in mouse upper jejunal epithelium using an Ussing chamber, immunocytochemistry and Ca2+ and Na+ imaging in single intestinal epithelial cells. KEY RESULTS Glucose induced jejunal Isc via Na+ -glucose cotransporter 1 (SGLT1) operated more efficiently in the presence of extracellular Ca2+ . A crosstalk between luminal Ca2+ entry via plasma Cav 1.3 channels and the ER Ca2+ release through ryanodine receptor (RYR) activation in small intestinal epithelial cell (IEC) or Ca2+ -induced Ca2+ release (CICR) mechanism was involve in Ca2+ -mediated jejunal glucose absorption. The ER Ca2+ release through RyR triggered basolateral Ca2+ entry or store-operated Ca2+ entry (SOCE) mechanism and the subsequent Ca2+ entry via Na+ /Ca2+ exchanger 1 (NCX1) were found to be critical in Na+ -glucose cotransporter-mediated glucose absorption. Blocking RyR, SOCE and NCX1 inhibited glucose induced [Na+ ]cyt and [Ca2+ ]cyt in single IEC and protein expression and co-localization of STIM1/Orai1, RyR1 and NCX1 were detected in IEC and jejunal mucosa. CONCLUSION AND IMPLICATIONS Luminal Ca2+ influx through Cav 1.3 triggers the CICR through RyR1 to deplete the ER Ca2+ , which induces the basolateral STIM1/Orai1-mediated SOCE mechanism and the subsequent Ca2+ entry via NCX1 to regulate intestinal glucose uptake via Ca2+ signalling. Targeting these mechanisms in IEC may help to modulate blood glucose and sodium in the metabolic disease. |
| تدمد: | 1476-5381 0007-1188 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6f870aa084ecc6fcb455fdae0206acd7 https://doi.org/10.1111/bph.15287 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........6f870aa084ecc6fcb455fdae0206acd7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765381 00071188 |
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