Insulin stimulates SGLT2-mediated tubular glucose absorption via oxidative stress generation

Diabetology & Metabolic Syndrome

Sho-ichi Yamagishi¹  Yuji Ishibashi¹  Takanori Matsui¹  Nobutaka Nakamura¹ 

[1] Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan

关键词: AGEs;    Diabetic nephropathy;    Insulin;    Oxidative stress;    SGLT2;   

Others  :  1211820
DOI  :  10.1186/s13098-015-0044-1

 received in 2015-04-07, accepted in 2015-05-20,  发布年份 2015

【 摘 要 】

Background

Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is expressed mainly on the apical membrane of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is enhanced under diabetic conditions, selective inhibition of SGLT2 has been proposed as a potential therapeutic target for the treatment of patients with diabetes. However, it remains unclear which diabetes-associated factors are involved in overexpression of SGLT2.

Methods

Therefore, in this study, we examined whether insulin, high glucose, advanced glycation end products (AGEs), or H₂O₂ stimulated SGLT2 expression in human cultured proximal tubular cells, and then investigated the underlying molecular mechanisms.

Results

High glucose or AGEs did not affect SGLT2 expression in tubular cells. Insulin significantly increased tubular SGLT2 level in a dose-dependent manner, whereas bell-shaped dose-response curves were observed for H₂O₂-treated cells. An anti-oxidant, N-acetylcysteine completely blocked insulin-induced up-regulation of SGLT2 as well as increase in glucose absorption by tubular cells. Furthermore, insulin dose-dependently increased reactive oxygen species generation in tubular cells.

Conclusions

Our present study demonstrated that insulin could stimulate SGLT-2-mediated glucose entry into cultured proximal tubular cells via oxidative stress generation. Suppression of the insulin-induced overexpression of SGLT2 in tubular cells might be a novel therapeutic strategy for the treatment of diabetic nephropathy.

【 授权许可】

   
2015 Nakamura et al.; licensee BioMed Central.

【 图 表 】

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