Insulin attenuates the inhibition effect of lipopolysaccharide on Na+-K+-ATPase α1 via PI3K/AKT and PI3K/ERK pathway

doi:10.12092/j.issn.1009-2501.2019.08.008

Abstract

Abstract:

AIM: To investigate the molecular mechanism of insulin alleviating the inhibition of lipopolysaccharide on the expression of Na+-K+-ATPase α1 subunit in pulmonary alveoli type II alveolar cells. METHODS: A549 cells, firstly induced by lipopolysaccharide (1 μg/mL) for 8 hours, were used as the research objects, then treated with insulin (100 nmol/L) for 4 hours. Western blot was used to detect the expression of Na+-K+-ATPase α1 subunit and AKT, ERK1/2, p70s6k, NEDD4-2 total protein expression and changes in their phosphorylation levels. RESULTS:The expression of Na+-K+-ATPase α1 subunit protein was significantly decreased in A549 cells when treated with 1 μg/mL lipopolysaccharide. Insulin treatment could partially relieve the lipopolysaccharide inhibition on the expression of Na+-K+-ATPase α1 subunit in A549 cells. Insulin up-regulation of Na+-K+-ATPase α1 subunit expression was achieved by altering the phosphorylation levels of the key proteins AKT, NEDD4-2, ERK1/2, and p70s6k in the PI3K/AKT and PI3K/ERK pathways.CONCLUSION: Insulin could partially relieve the lipopolysaccharide inhibition on the expression of Na+-K+-ATPase α1 subunit in pulmonary alveoli type II alveolar cells by regulating the PI3K/AKT and PI3K/ERK pathways, which provided a preliminary experimental basis for the clinical use of insulin to intervene in acute respiratory distress syndrome.

Key words: insulin, lipopolysaccharide, acute respiratory distress syndrome, Na+-K+-ATPase α1, PI3K pathway

CLC Number:

R965.2

LIU Huanmiao, CHEN Zhuohui, WU Di, HUANG Xueting, WAN Qiquan. Insulin attenuates the inhibition effect of lipopolysaccharide on Na+-K+-ATPase α1 via PI3K/AKT and PI3K/ERK pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(8): 896-902.

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