Loss of renal SNX5 results in impaired IDE activity and insulin resistance in mice
作者： Fengmin Li , Jian Yang , Van Anthony M. Villar , Laureano D. Asico , Xiaobo Ma
DOI: 10.1007/S00125-017-4482-1
关键词:
摘要: We hypothesised that renal sorting nexin 5 (SNX5) regulates the insulin-degrading enzyme (IDE) and, thus, circulating insulin levels. therefore studied dynamic interaction between SNX5 and IDE in human proximal tubule cells (hRPTCs), as well rat mouse kidneys. The regulation of by expressed kidney was vitro vivo. Snx5 or mock siRNA added to immortalised hRPTCs (passage <20) culture selectively infused, via osmotic mini-pump, into remnant uninephrectomised mice rats. co-localised with at plasma membrane perinuclear area brush border tubules human, rat, Insulin increased co-localisation co-immunoprecipitation hRPTCs. Silencing decreased expression activity. Renal-selective silencing (SNX5 protein: 100 ± 25 vs 29 ± 10, p < 0.05 [% control]) C57Bl/6J protein (100 ± 13 57 ± 6, urinary excretion, impaired responses glucose, blood glucose Spontaneously hypertensive rats (SHRs) had levels (100 ± 27 29 ± 6, (100 ± 5 75 ± 4, proteins, compared normotensive Wistar–Kyoto (WKY) Kidney Snx5-depleted WKY also RPTCs from SHRs humans volunteers, indicating a common cause for hyperinsulinaemia hypertension. Renal positively function. This study is first demonstrate novel crucial role metabolism.
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