Che Bian, Ruijing Zhang, Yuxia Wang, Jia Li, Yuling Song, Dan Guo, Jing Gao, Huiwen Ren
Molecular and cellular endocrinology 2022 May 01The purpose of this study was to explore the expression changes of Sirtuin 6 in diabetic renal tissues and the molecular mechanisms affecting renal tubular gluconeogenesis and reabsorption. The type 1 diabetic C57BL/6 mice model as well as high glucose cultured proximal tubular cells and cell lines were established. Sirt6 siRNA, the SGLT2 inhibitor (dapagliflozin), and insulin were pre-treated to make Sirtuin 6 levels, gluconeogenesis, and reabsorption changes. Immunofluorescence was used for Sirtuin 6 renal localization, and molecular biological detection was adopted for transcription factors, FoxO1, transporters (SGLT2 and GLUT2) as well as rate-limiting enzyme. Nuclear/plasma proteins were extracted to detect Sirtuin 6 and FoxO1 levels in the subcellular structure. Sirtuin 6 was decreased in STZ-induced diabetic renal outer medulla, and lower both in high glucose-induced primary proximal tubular cells and cell lines. Sirtuin 6 reversed the glucose reabsorption and gluconeogenesis effect via regulating FoxO1 and affecting nuclear translocation of FoxO1 in high glucose-induced proximal tubular cells. Sirtuin 6 affects renal glucose reabsorption and gluconeogenesis in type 1 diabetes by regulating FoxO1 nuclear import. Copyright © 2022 Elsevier B.V. All rights reserved.
Che Bian, Ruijing Zhang, Yuxia Wang, Jia Li, Yuling Song, Dan Guo, Jing Gao, Huiwen Ren. Sirtuin 6 affects glucose reabsorption and gluconeogenesis in type 1 diabetes via FoxO1. Molecular and cellular endocrinology. 2022 May 01;547:111597
PMID: 35157928
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