A short–term pretreatment with insulin and glucose efficiently protected the kidney against Ischemia-Reperfusion injury via the P-AKT-Bax-Caspase-3 signaling pathway in mice

Abstract

Objective This study investigated whether pretreatment with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI). Methods Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by re-perfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the pretreatment duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days. Results Pretreatment with insulin and glucose protected the kidney against IRI through a decrease in Cr and BUN concentration in plasma and a reduction of kidney injuries. The protection effect was related to the signaling pathway of P-AKT-BAX-caspase-3. An AKT inhibitor partially reversed the protective effects of insulin pretreatment. The pretreatment duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology. Conclusion A short-term pretreatment with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term pretreatment provides a practicable strategy for protecting the kidney against predictable IRI, such as major operations with high hypotension incidence.