Autocrine modulation of glucose transporter SGLT2 by IL-6 and TNF-alpha in LLC-PK1 cells

作者:Maldonado Cervantes M I; Galicia O G; Moreno Jaime B; Zapata Morales J R; Montoya Contreras A; Bautista Perez R; Martinez Morales F*
来源:Journal of Physiology and Biochemistry, 2012, 68(3): 411-420.
DOI:10.1007/s13105-012-0153-3

摘要

We determined in cultured kidney epithelial cells (LLC-PK1) the effects of high glucose, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) on mRNA and protein expression of the renal glucose transporters SGLT1 and SGLT2. Cultured monolayers were incubated with similar concentrations of IL-6 and TNF-alpha to those produced by LLC-PK1 in the presence of 20 mM glucose. Confluent monolayers with either 5 (controls, C) or 20 mM glucose (high glucose, HG) were incubated in the presence of 5 mM glucose, 20 mM glucose, 10 pg/ml IL-6, or TNF-alpha alone or in combination. Separate groups with IL-6 and TNF-alpha were incubated with antibodies to their respective receptors. HG induced an increased SGLT1 mRNA at 48 h (p < 0.05 vs. C) and protein expression in 120 h (p < 0.05 vs. C). HG also induced an increased SGLT2 mRNA at 72 and 96 h (P < 0.05 vs. C) and SGLT2 protein expression at 120 h (p < 0.05 vs. C). In C, 10 pg/ml IL-6 or TNF-alpha did not modify SGLT1 mRNA (n.s vs. in the absence of cytokines). In contrast, cytokines induced an increased expression of SGLT1 protein at 120 h (p < 0.05 vs. in the absence of cytokines), and SGLT2 mRNA and protein were increased at 96 and 120 h, respectively (p < 0.05 vs. in absence of cytokines). No changes were observed when cells were incubated with cytokines and HG (n.s vs. C). In conclusion, this study showed that SGLT2 increased in the presence of IL-6 and TNF-alpha, indicating an autocrine modulation of the expression of this transporter by cytokines.

  • 出版日期2012-9