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10.3945/jn.115.213918

http://scihub22266oqcxt.onion/10.3945/jn.115.213918
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26355001!ä!26355001

suck abstract from ncbi


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pmid26355001      J+Nutr 2015 ; 145 (11): 2440-7
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  • Insulin Modulates the Na+/Mg2+ Exchanger SLC41A1 and Influences Mg2+ Efflux from Intracellular Stores in Transgenic HEK293 Cells #MMPMID26355001
  • Mastrototaro L; Tietjen U; Sponder G; Vormann J; Aschenbach JR; Kolisek M
  • J Nutr 2015[Nov]; 145 (11): 2440-7 PMID26355001show ga
  • BACKGROUND: Magnesium deficiency is a common complication of diabetes with an unclear molecular background. OBJECTIVE: We investigated the effect of the insulin (INS)-signaling pathway (ISP) on the regulation of Mg(2+) efflux (Mg(2+)E) conducted by solute carrier family 41, member A1 (SLC41A1; activated by protein kinase A) in transgenic human embryonic kidney (HEK) 293 cells. METHODS: HEK293 cells overexpressing SLC41A1 were loaded with the Mg(2+) fluorescent indicator mag-fura-2 and Mg(2+). Measurements of Mg(2+)E were conducted in Mg(2+)-free buffer by using fast-filter fluorescence spectrometry. We examined the effects of INS, inhibitors of ISP or p38 mitogen-activated protein kinase (p38 MAPK), an activator of adenylate cyclase (ADC), and their combinations on SLC41A1-attributed Mg(2+)E. RESULTS: The application of 400 muU/mL INS inhibited SLC41A1-mediated Mg(2+)E by up to 50.6% compared with INS-untreated cells (P < 0.001). Moreover, INS evoked the early onset of Mg(2+) release from intracellular stores. The application of 0.1 muM wortmannin or 10 muM zardaverine (both ISP inhibitors) restored SLC41A1 Mg(2+)E capacity in the presence of INS to the same levels in INS-untreated cells. The simultaneous application of 10 muM forskolin, an ADC activator, and INS resulted in a reduction of Mg(2+)E of up to 59% compared with untreated cells (P < 0.001), which was comparable to that in cells treated with INS alone. Inhibition of p38 MAPK with 10 muM SB 202190 (SB) in the absence of INS resulted in a decrease (P < 0.001) of SLC41A1-dependent Mg(2+)E (by up to 49%) compared with Mg(2+)E measured in untreated cells. Simultaneous exposure of cells to SB and INS had a stronger inhibitory effect on SLC41A1 activity than INS alone (P < 0.05). CONCLUSIONS: INS affects intracellular Mg(2+) concentration in transgenic HEK293 cells by regulating SLC41A1 activity (via ISP) and by influencing the compartmentalization and cellular distribution of Mg(2+). In addition, p38 MAPK activates SLC41A1 independently of INS action.
  • |Adenylyl Cyclases/metabolism[MESH]
  • |Androstadienes/pharmacology[MESH]
  • |Cation Transport Proteins/genetics/*metabolism[MESH]
  • |Colforsin/pharmacology[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |HEK293 Cells[MESH]
  • |Humans[MESH]
  • |Insulin/*metabolism[MESH]
  • |Magnesium/*metabolism[MESH]
  • |Pyridazines/pharmacology[MESH]
  • |Signal Transduction[MESH]
  • |Spectrometry, Fluorescence[MESH]
  • |Wortmannin[MESH]


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